Summary of COVID-19 hydroxychloroquine studies
Global HCQ/CQ studies
November 20, 2024
@CovidAnalysis
November 20, 2024
@CovidAnalysis
Studies
Meta Analysis
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RCT 4,652 low-risk participants, published days after completion, showing significantly lower PCR+ COVID-19 cases with HCQ/CQ prophylaxis, p = 0.0004. Authors include a meta-analysis of this and 11 other RCTs confirming significantly lower COVID-19 cases. Authors conclude that HCQ/CQ could have been deployed with benefit early in the pandemic. HCQ/CQ was well tolerated with no serious drug-related adverse events. There were significantly fewer severe adverse events with treatment. (Serious adverse events refer to serious outcomes while severe adverse events refer to intensity, e.g., severe headache). Authors note that "the primary outcome was subsequently changed to include seroconversion" rather than only PCR+ cases. The date of this change is not reported. The PCR+ results are the most reliable. Inclusion of seroconversion means that participants with asymptomatic COVID-19 and symptomatic non-COVID-19 infections will be counted as symptomatic COVID-19 cases...
Sep 2024, PLOS Medicine, https://journals.plos.org/plosone/article?id=10.1371/journal.pmed.1004428, https://c19p.org/schilling3
HCQ early treatment study: 85% lower progression (p=0.006), 24% faster improvement (p=0.02), and 36% improved viral clearance (p=0.001).
85% lower disease progression with early use of HCQ. Retrospective 616 patients in China showing adjusted progression HR 0.15, p = 0.006.
Dec 2020, BioScience Trends, https://www.jstage.jst.go.jp/article/bst/advpub/0/advpub_2020.03340/_article/-char/ja/, https://c19p.org/su
754 patient HCQ late treatment RCT: 66% improved viral clearance (p<0.0001).
RCT 754 patients comparing HCQ+AZ along with other treatment groups using lopinavir/ritonavir and doxycycline to a control group taking AZ, finding significantly faster viral clearance with all treatment groups. (The labels in Figure 2 appear to be reversed).
Feb 2021, Biochemistry Research Int., https://www.hindawi.com/journals/bri/2021/6685921/, https://c19p.org/purwati
Observational prospective 5,541 patients, adjusted HCQ mortality odds ratio OR 0.36, p = 0.012. Adjusted hospitalization OR 0.57, p < 0.001. Zinc supplementation was used in all cases. Early treatment in ambulatory fever clinics in Saudi Arabia.
Sep 2020, medRxiv, https://www.medrxiv.org/content/10.1101/2020.09.09.20184143v1, https://c19p.org/sulaiman
Prophylaxis RCT in Singapore with 3,037 low risk patients, showing lower serious cases, lower symptomatic cases, and lower confirmed cases of COVID-19 with all treatments (ivermectin, HCQ, PVP-I, and Zinc + vitamin C) compared to vitamin C. Only 71.4% reported >70% adherence, limiting efficacy. QTc did not statistically significantly differ between baseline and follow-up readings (mean 379 vs 378ms, paired t-test p=0.387). Meta-analysis of vitamin C in 6 previous trials shows a benefit of 16%, so the actual benefit of ivermectin, HCQ, and PVP-I may be higher. Cluster RCT with 40 clusters. There were no hospitalizations and no deaths.
Apr 2021, Int. J. Infectious Diseases, https://www.ijidonline.com/article/S1201-9712(21)00345-3/fulltext, https://c19p.org/seeth
100% reduction in hospitalization and cases with early treatment using HCQ+AZ+zinc. Brief report on healthcare workers in Bulgaria. 0 hospitalizations with treatment vs. 2 for control 0 PCR+ at day 14 with treatment vs. 3 for control 33 treatment patients and 5 control patients. No serious adverse events. This paper reports on both PEP and early treatment, we have separated the two studies.
Nov 2020, New Microbes and New Infections, https://www.sciencedirect.com/science/article/pii/S2052297520301657, https://c19p.org/simova
PSM prospective study of 260 COVID-19 patients in Bulgaria, showing lower mortality, ventilation, and ICU admission with HCQ treatment.
Mar 2022, Infectious Disorders - Drug Targets, https://www.eurekaselect.com/article/121288, https://c19p.org/tsanovska
Retrospective 2,882 patients in China, median age 62, 278 receiving HCQ, median 10 days post hospitalization, showing that HCQ treatment can reduce systemic inflammation and inhibit the cytokine storm, thus protecting multiple organs from inflammatory injuries, such as detoxification in the liver and attenuation of cardiac injury. IL-6 levels significantly reduced after HCQ treatment, p<0.05, and elevated after HCQ withdrawal. The significantly lower dose used here is potentially related to the different observations from the RECOVERY trial results. Authors suggest that treatment should be started as soon as possible. The 550 patients that were critically ill at baseline are reported in a separate paper. For the non-critically-ill patients at baseline, the proportion of patients that became critically ill was significantly lower for those treated with HCQ. For the subset of patients that started HCQ treatment early only 1.4% died versus 3.9% for HCQ started late and 9.1% for control..
Aug 2020, Science China Life Sciences, 2020 Aug 3, https://link.springer.com/article/10.1007/s11427-020-1782-1, https://c19p.org/yu2
HCQ 1-4 days from diagnosis was the only protective factor against prolonged viral shedding found, OR 0.111, p=0.001. 57.1% viral clearance with 1-4 days delay vs. 22.9% for 5+ days delayed treatment. Authors report that early administration of HCQ significantly ameliorates inflammatory cytokine secretion and that COVID-19 patients should be administrated HCQ as soon as possible. 42 patients with HCQ 1-4 days from diagnosis, 48 with HCQ 5+ days from diagnosis.
Jul 2020, Infection & Chemotherapy, 2020, https://icjournal.org/DOIx.php?id=10.3947/ic.2020.52.3.396, https://c19p.org/hong
62 patients. RCT showing significantly faster recovery with HCQ. 13% progressed to severe cases in the control group, versus 0% for the treatment group. Significant improvement seen in pneumonia on chest CT for 61% of treated patients and 16% of control patients.
Mar 2020, medRxiv, https://www.medrxiv.org/content/10.1101/2020.03.22.20040758v3, https://c19p.org/chenrct
441 patient HCQ late treatment RCT: 24% lower hospitalization (p=0.57) and 4% improved viral clearance (p=0.1).
Early terminated RCT in Brazil showing lower mortality and hospitalization with HCQ, but not reaching statistical significance. Although the title includes "early treatment", treatment was relatively late, with most patients being over 5 days from the onset of symptoms. Adverse events were lower in the HCQ group compared to the control group. This trial appears to have been terminated at 45% enrollment while showing ≥70% probability of superiority. The futility threshold was not reported, but it would be highly unusual for it to be as high as 70% [doyourownresearch.substack.com]. The paper indicates the placebo was talc, however the trial protocol shows the "placebo" as vitamin C, for which there are 7 COVID-19 treatment studies as of April 2021 that collectively show significant efficacy. Results differ significantly from those reported prior to publication. Prior to publication, authors reported an RR for hospitalization or death of 1.0 [0.45-2.21] [ajtmh.org].
Apr 2021, JAMA Network Open, https://jamanetwork.com/journals/jamanetworkopen/fullarticle/2779044, https://c19p.org/reis
Retrospective 10,429 outpatients in France, 8,315 treated with HCQ+AZ a median of 4 days from symptom onset, showing significantly lower mortality with treatment.
May 2021, Reviews in Cardiovascular Medicine, https://www.imrpress.com/journal/RCM/22/3/10.31083/j.rcm2203116, https://c19p.org/million4
RCT 48 hospitalized patients in China showing faster clinical recovery and viral clearance with CQ/HCQ.
Jun 2020, medRxiv, https://www.medrxiv.org/content/10.1101/2020.06.19.20136093v1, https://c19p.org/chen
RCT 143 healthcare workers in Iran, showing lower cases with HCQ prophylaxis, statistically significant only for moderate/severe cases. Baseline details are not provided.
Jan 2023, Advanced Biomedical Research, https://www.advbiores.net/article.asp?issn=2277-9175;year=2023;volume=12;issue=1;spage=3;epage=3;aulast=Nasri, https://c19p.org/nasri
864 patient HCQ late treatment study: 80% lower mortality (p<0.0001), 20% lower progression (p=0.43), and 31% faster viral clearance (p=0.26).
Retrospective 863 COVID-19 patients in Burkina Faso, showing lower mortality, lower progression for outpatients, and faster viral clearance with HCQ/CQ treatment. Only the lower mortality was statistically significant. NCT04445441.
Feb 2022, Int. J. Infectious Diseases, https://www.sciencedirect.com/science/article/pii/S1201971222001114, https://c19p.org/rouamba
For positive symptomatic cases, a greater effect is seen for nursing home residents, RR=0.49 [0.21 - 1.17], vs. overall 0.89, possibly because the exposure events are identified faster in this context, versus home exposure where testing of the source may be more delayed. The trial is too small for significance here. If the trend continued this result would be significant at p<0.05 after about 25% more patients were added. There are 2 groups in this study: PCR+ at baseline (n=314) and PCR- at baseline (n=2000), which should be separated as they are different populations (primary outcome rates 18.6% and 22.2% compared to 3.0% and 4.3%). PCR+ already have COVID-19, so PEP analysis should be for the 2,000 PCR-, showing symptomatic COVID-19 of 4.3% (control) and 3.0% (treatment), RR 0.7, p=0.154. The paper has different RR values here, stating that they are adjusted for contact-level variables. It is not clear how they are computed - the adjusted RR for the overall sample is 4% lower, for..
Jul 2020, NEJM, https://www.nejm.org/doi/full/10.1056/NEJMoa2021801, https://c19p.org/mitjapep
RCT late stage severe condition (93% SOFA ≥ 2, 96% APACHE ≥ 8) high comorbidity hospitalized patients in Mexico with 33 HCQ and 37 control patients not finding significant differences. NCT04391127.
Feb 2021, Infectious Disease Reports, https://www.mdpi.com/2036-7449/14/2/20, https://c19p.org/beltrangonzalezh
Retrospective 565 COVID-19 patients in India, showing lower mortality with HCQ+AZ treatment. Most patients (66%) had mild disease at baseline.
May 2023, The J. the Association of Physicians of India, https://pubmed.ncbi.nlm.nih.gov/37355843/, https://c19p.org/rathod2
100 patient HCQ early treatment study: 96% lower mortality (p=0.004).
Retrospective 100 COVID+ elderly nursing home patients, HCQ+AZ mortality 11.4% vs. control 61.9%, RR 0.18, p<0.001. Median age 85.
Sep 2020, European Geriatric Medicine, https://link.springer.com/article/10.1007/s41999-020-00432-w, https://c19p.org/heras
Retrospective 272 nursing home residents showing significantly improved survival after establishing a treatment program including HCQ with or without lopinavir/ritonavir and with the addition of adjuvant and antimicrobial treatments depending on circumstances. HCQ (114 patients), HCQ+LPV/RTV (18 patients), and HCQ+AZ (7 patients). Dosage details are in the supplementary appendix.
Jul 2020, J. Gerontol. A Biol. Sci. Med. Sci., https://academic.oup.com/biomedgerontology/advance-article/doi/10.1093/gerona/glaa192/5879759, https://c19p.org/bernabeuwittel
Early terminated RCT with only 20 patients.
Jul 2020, Novartis, NCT04358081, https://clinicaltrials.gov/study/NCT04358081, https://c19p.org/novartis
435 patient HCQ prophylaxis RCT: 51% fewer symptomatic cases (p=0.79) and 27% fewer cases (p=0.31).
Early terminated healthcare worker prophylaxis RCT in Spain, showing lower risk of symptomatic cases with HCQ prophylaxis, without statistical significance due to the small number of events.
Aug 2022, Clinical Microbiology and Infection, https://www.sciencedirect.com/science/article/pii/S1198743X22003706, https://c19p.org/polo
Small early terminated late stage (60% on oxygen) RCT in France showing 46% lower mortality. mortality at 28 days relative risk RR 0.54 [0.21-1.42] combined mortality/intubation at 28 days relative risk RR 0.74 [0.33-1.70] If not stopped early and the same trend continued, statistical significance would be reached on 28 day mortality after ~550 patients (1,300 patients were planned). Mortality results are not provided for subgroups. For the subgroups receiving AZ: No safety concerns were identified. This study has been presented as negative, however the results do not support that conclusion.
Oct 2020, Clinical Microbiology and Infection, https://www.sciencedirect.com/science/article/pii/S1198743X21001403, https://c19p.org/dubee
Tiny early-terminated 34 patient RCT for outpatient treatment showing faster recovery with treatment (not statistically significant). All patients recovered (3 control patients recovered after crossover to the treatment arm) - as per protocol mid-recovery results have priority. There was no mortality and only one hospitalization on day 0 before treatment. There were no severe adverse events.
Feb 2021, medRxiv, https://www.medrxiv.org/content/10.1101/2021.02.22.21252228v1, https://c19p.org/amaravadi
RCT 471 mild COVID-19 patients in Pakistan showing no significant differences in clinical improvement and viral clearance between HCQ, azithromycin, oseltamivir, and combinations. Mortality was significantly lower in HCQ vs. non-HCQ arms. The best results for viral clearance and clinical improvement were seen with the combination of all treatments. There was no control group. No serious adverse events were reported. All patients had mild COVID-19 and the paper indicates early treatment, however time from onset is not reported and minimal baseline information is provided.
Mar 2024, Pakistan J. Medical Sciences, https://www.pjms.org.pk/index.php/pjms/article/view/8757, https://c19p.org/azhar
79% lower mortality and 82% lower hospitalization with early HCQ+AZ+Z. No cardiac side effects. Retrospective 518 patients (141 treated, 377 control).
Jul 2020, Int. J. Antimicrobial Agents, https://www.sciencedirect.com/science/article/pii/S0924857920304258, https://c19p.org/derwand
Mean clinical recovery time reduced from 26 days (SOC) to 9 days, p<0.0001 (HCQ+AZ) or 13 days, p<0.0001 (AZ). No cardiac toxicity. Small retrospective study of 88 patients with case control analysis with matched patients.
May 2020, Asian J. Medicine and Health, https://www.journalajmah.com/index.php/AJMAH/article/view/30224, https://c19p.org/guerin
RCT of 1,000 people showing lower risk of COVID-19 infection with HCQ prophylaxis. There was no significant difference in side effects or adherence, no severe side effects, and blinding was well maintained. There are now PrEP RCTs, showing significant efficacy for COVID-19 cases with .
Jan 2024, Social Determinants of Health, https://journals.sbmu.ac.ir/sdh/article/view/43032, https://c19p.org/chouhdari
3,462 patient HCQ late treatment study: 93% lower mortality (p<0.0001).
Retrospective 3,462 hospitalized COVID-19 patients across 13 states in Nigiera, showing lower mortality with HCQ. Authors note that the improved results compared with many other late stage studies may be related to the dose and experience of the physicians - in other studies beneficial effects may be offset by the side effects of high cumulative doses in late stage patients. Authors also note the worse results with a combination of CQ/HCQ and AZ may be related to the side effects becoming more significant for late stage patients.
May 2023, Nigerian Medical J., https://nigerianmedjournal.org/index.php/nmj/article/view/174, https://c19p.org/yilgwan
Prospective analysis of 95 Lupus Nephritis patients in Romania, showing lower risk of COVID-19 with HCQ use.
Sep 2022, Biomedicines, https://www.mdpi.com/2227-9059/10/10/2423, https://c19p.org/obrisca
Retrospective 15,968 COVID-19 hospitalized patients in Spain, showing lower mortality with existing use of several medications including metformin, HCQ, azithromycin, aspirin, vitamin D, vitamin C, and budesonide. Since only hospitalized patients are included, results do not reflect different probabilities of hospitalization across treatments.
Aug 2022, Virology J., https://virologyj.biomedcentral.com/articles/10.1186/s12985-023-02195-9, https://c19p.org/loucera3h
Prophylaxis study with 12,089 Indian healthcare workers, showing lower risk of COVID-19 cases with treatment, and increasingly lower risk for longer durations of HCQ prophylaxis. The appendices are not currently available.
Jun 2021, J. the Association of Physicians of India, June 2021, https://www.researchgate.net/publication/357700064_Hydroxychloroquine_for_SARS_CoV2_Prophylaxis_in_Healthcare_Workers_-_A_Multicentric_Cohort_Study_Assessing_Effectiveness_and_Safety, https://c19p.org/badyal
Early terminated HCQ PrEP RCT with 62 HCQ and 65 placebo patients, showing 82% lower cases with treatment, p = 0.12. If the trial is continued and the same event rate is observed, statistical significance will be reached after adding about 16 patients per arm.
May 2021, PLOS ONE, https://journals.plos.org/plosone/article?id=10.1371/journal.pone.0261980, https://c19p.org/rojasserrano
Retrospective 3,044 hospitalized COVID-19 patients in Italy, showing HCQ significantly associated with survival in light, mild, and moderate cases in multivariable analysis, but not in severe cases.
Apr 2021, Internal and Emergency Medicine, https://link.springer.com/article/10.1007/s11739-021-02742-8, https://c19p.org/corradini
73% lower mortality with HCQ. Analysis of 98 PCR+ nursing home residents in Italy, mean age 90, showing HCQ mortality RR 0.27, p = 0.03. Subject to confounding by contraindication. The paper provides the p value for regression but not the effect size.
Dec 2020, Aging, https://www.aging-us.com/article/202307/text, https://c19p.org/cangiano
Retrospective 300 hospitalized patients in Saudi Arabia showing HCQ adjusted odds ratio aOR 0.12, p < 0.001.
Nov 2020, Diabetes Research and Clinical Practice, https://www.sciencedirect.com/science/article/pii/S0168822720307956, https://c19p.org/sheshah
100% reduction in cases with HCQ+zinc post-exposure prophylaxis. Brief report for healthcare workers in Bulgaria. 0 cases with treatment vs. 3 for control. 156 treatment patients and 48 control patients. No serious adverse events. This paper reports on both PEP and early treatment, we have separated the two studies.
Nov 2020, New Microbes and New Infections, https://www.sciencedirect.com/science/article/pii/S2052297520301657, https://c19p.org/simovapep
90% reduction in cases with HCQ pre-exposure prophylaxis. Retrospective 604 healthcare workers.
Nov 2020, J. Marine Medical Society, https://www.marinemedicalsociety.in/preprintarticle.asp?id=300159, https://c19p.org/mathai
Retrospective 72 pediatric patients showing HCQ associated with a shorter duration of fever (p=0.023), less progression (p=0.016), and fewer return visits to the ER (p=0.017).
Nov 2020, Annals of Pediatrics, https://www.sciencedirect.com/science/article/pii/S1695403320304768, https://c19p.org/lopez2
Retrospective 377 patients, 73% reduction in mortality with HCQ+AZ, adjusted hazard ratio HR 0.27 [0.17-0.41]. Mean age 71.8. No serious adverse events. Subject to incomplete adjustment for confounders.
Sep 2020, Clinical and Translational Science, https://ascpt.onlinelibrary.wiley.com/doi/abs/10.1111/cts.12860, https://c19p.org/lauriola
Analysis of 1641 systemic autoimmune disease patients showing csDMARD (HCQ etc.) RR 0.37, p=0.015. csDMARDs include HCQ, CQ, and several other drugs, so the effect of HCQ/CQ alone could be higher. This study also confirms that the risk of COVID-19 for systemic autoimmune disease patients is much higher overall, OR 4.42, p<0.001 (this is the observed real-world risk which takes into account factors such as these patients potentially being more careful to avoid exposure). (results are for "definite + highly suspected" cases and the main result is presented in the paper as the OR for not taking csDMARDs, we have converted this to RR for taking csDMARDs).
Aug 2020, Clinical Rheumatology, https://link.springer.com/article/10.1007/s10067-020-05334-7, https://c19p.org/ferri
36 patient HCQ late treatment study: 88% lower ICU admission (p=0.008).
Retrospective analysis of 36 hospitalized patients showing HCQ/AZ associated with lower ICU admission, p=0.008. Median age 66, no mortality. Confounding by indication, however it was patients with hypoxemic pneumonia that were treated with HCQ/AZ, patients were not treated with HCQ/AZ if they didn't need oxygen therapy.
Aug 2020, J. Global Antimicrobial Resistance, https://www.sciencedirect.com/science/article/pii/S221371652030206X, https://c19p.org/dubernet
Prophylaxis study with 334 low-risk healthcare workers in India, showing significantly lower risk of cases with treatment. Symptomatic patients received PCR results, but only some asymptomatic patients did, so there may have been additional asymptomatic cases. There were no severe adverse events.
Jul 2020, J. Family Medicine and Primary Care, https://journals.lww.com/10.4103/jfmpc.jfmpc_1177_21, https://c19p.org/kadnur
Rheumatic disease patients on HCQ had a lower risk of COVID-19 than those on other disease-modifying anti-rheumatic drugs, OR 0.09 (0.01–0.94), p=0.044 after adjusting for age, sex, smoking, systemic lupus erythematosus, infection in other family members, and comorbidities. 43 patients with rheumatic disease and COVID-19 exposure.
Jul 2020, Lancent Rheumatology, https://www.thelancet.com/journals/lanrhe/article/PIIS2665-9913(20)30227-7/fulltext, https://c19p.org/zhong
Retrospective 17 hospitalized lung cancer patients showing lower mortality with HCQ+AZ treatment.
May 2020, Lung Cancer, https://www.lungcancerjournal.info/article/S0169-5002(20)30468-2/fulltext, https://c19p.org/rogado
4+ doses of HCQ associated with a significant decline in the odds of getting infected, dose-response relationship exists.
May 2020, Indian J. Medical Research, https://www.ijmr.org.in/article.asp?issn=0971-5916;year=2020;volume=151;issue=5;spage=459;epage=467;aulast=Chatterjee, https://c19p.org/chatterjee
197 CQ patients, 176 control. Mean time to undetectable viral RNA and duration of fever significantly reduced. No serious adverse events.
May 2020, National Science Review, https://academic.oup.com/nsr/advance-article/doi/10.1093/nsr/nwaa113/5848167, https://c19p.org/huangnsr
Retrospective, 550 critically ill patients. 19% fatality for HCQ versus 47% for non-HCQ, RR 0.395, p=0.002. The levels of inflammatory cytokine IL-6 were significantly reduced from 22.2 pg/mL to 5.2 pg/mL (p<0.05) at the end of the treatment in the HCQ group but there was no change in the control group.
May 2020, Science China Life Sciences, 2020 May 15, 1-7, https://link.springer.com/article/10.1007%2Fs11427-020-1732-2, https://c19p.org/yu
ICMR seroprevalence survey of 500 healthcare workers in India, 279 taking HCQ prophylaxis, showing a significantly lower risk with treatment, and lower severity.
Sep 2020, ResearchGate, https://www.researchgate.net/publication/344221734_Sero-survey_for_health-care_workers_provides_corroborative_evidence_for_the_effectiveness_of_Hydroxychloroquine_prophylaxis_against_COVID-19_infection, https://c19p.org/yadav3
Retrospective 28,759 adult outpatients with mild COVID-19 in Iran, 7,295 treated with HCQ, showing significantly lower hospitalization and mortality with treatment.
Apr 2021, Int. Immunopharmacology, https://www.sciencedirect.com/science/article/pii/S1567576921002721, https://c19p.org/mokhtari
RCT with 54 favipiravir, 51 HCQ, and 52 SOC hospitalized patients in Bahrain, showing no significant differences. Viral clearance improved with both treatments, but did not reach statistical significance with the small sample size.
Mar 2022, Scientific Reports, https://www.nature.com/articles/s41598-022-08794-w, https://c19p.org/alqahtani2
Retrospective 1,274 outpatients, 47% reduction in hospitalization with HCQ with propensity matching, HCQ OR 0.53 [0.29-0.95]. Sensitivity analyses revealed similar associations. Adverse events were not increased (2% QTc prolongation events, 0% arrhythmias).
Aug 2020, BMC Infectious Diseases, https://bmcinfectdis.biomedcentral.com/articles/10.1186/s12879-021-05773-w, https://c19p.org/ip
296 patient HCQ early treatment study: 81% lower mortality (p=0.21), 95% lower ventilation (p=0.0008), and 98% lower hospitalization (p<0.0001).
Comparison of HCQ, nitazoxanide, and ivermectin showing similar effectiveness for overall clinical outcomes in COVID-19 when used before seven days of symptoms, and overwhelmingly superior compared to the untreated COVID-19 population, even for those outcomes not influenced by placebo effect, at least when combined with azithromycin, and vitamin C, D and zinc in the majority of the cases. 585 patients with mean treatment delay 2.9 days. There was no hospitalization, mechanical ventilation, or mortality with treatment. Control group 1 was a retrospectively obtained group of untreated patients of the same population.
Nov 2020, New Microbes and New Infections, https://www.sciencedirect.com/science/article/pii/S2052297521000792, https://c19p.org/cadegiani
Low dose low-risk patient HCQ PEP RCT, showing lower symptomatic cases with treatment, without statistical significance. There were no moderate or severe cases. HCQ 800mg on day one followed by 400mg once weekly for 3 weeks.
Jan 2023, Scientific Reports, https://www.nature.com/articles/s41598-022-26053-w, https://c19p.org/dhibar2
Retrospective analysis of retirement homes, HCQ+AZ >= 3 days mortality OR 0.37, p=0.02. 1,690 elderly residents (mean age 83), 226 infected residents, 116 treated with HCQ+AZ >= 3 days. Detection via mass screening also showed significant improvements (16.9% vs. 40.6%, OR 0.20, p=0.001), suggesting that earlier detection and treatment is more successful.
Aug 2020, Int. J. Antimicrobial Agents, https://www.sciencedirect.com/science/article/abs/pii/S0924857920304301, https://c19p.org/ly
Update: we have not received details for treatment delay. An author reports that treatment initiation time was not recorded: [osf.io]. Conflicting estimates are provided in a comment of the article and independent analysis, with reports indicating missing data in the dataset. Also see [medrxiv.org] (companion PEP trial), and Pullen et al. [ncbi.nlm.nih.gov], which shows shipping delay for these trials of 19 - 68 hours. Only one third of participants completed enrollment weekdays between 8:00am and 4:00pm, with 44% outside of these hours during the week, and 22% during the weekend. With enrollment up to 4 days after symptom onset, this implies delivery 19 - 164 hours after onset (19 hours would require instantaneous enrollment). ~70 to 140 hour (inc. shipping) delayed outpatient treatment with HCQ showing lower hospitalization/death and faster recovery, but not reaching statistical significance. There was one hospitalized control death and one non-hospitalized HCQ death. It is unclear..
Jul 2020, Annals of Internal Medicine, https://www.acpjournals.org/doi/10.7326/M20-4207, https://c19p.org/skipper
Early terminated NIAID RCT for HCQ. Patients >60 were only in the HCQ arm. 57% of patients were high risk in the HCQ arm vs. 22% for control. Treatment started up to 20 days after symptoms.
Jul 2020, NCT04358068, https://clinicaltrials.gov/study/NCT04358068, https://c19p.org/smith2
97 patient HCQ late treatment study: 51% shorter hospitalization (p=0.01) and 56% faster viral clearance (p=0.005).
Retrospective of 97 moderate cases. Time to viral clearance significantly shorter for HCQ+antibiotic. Preprint withdrawn pending peer review.
May 2020, medRxiv, https://www.medrxiv.org/content/10.1101/2020.05.13.20094193v1?versioned=true, https://c19p.org/kim
PSM retrospective 6,217 hospitalized patients in Spain, showing lower mortality with HCQ. The higher efficacy reported with obesity is consistent with the greater efficacy predicted for higher cholesterol [Yuan].
Sep 2022, Anti-Infective Agents, https://www.eurekaselect.com/204783/article, https://c19p.org/nunezgil2
Retrospective 1,606 SLE patients showing lower risk of severe COVID-19 outcomes with HCQ/CQ use.
Feb 2022, Annals of the Rheumatic Diseases, https://ard.bmj.com/content/early/2022/02/15/annrheumdis-2021-221636.long, https://c19p.org/ugartegil
Lopinavir/ritonavir retrospective study also showing univariate results for HCQ, with significantly lower mortality.
Feb 2021, J. Infection, https://www.sciencedirect.com/science/article/pii/S0163445321000773, https://c19p.org/loratamayo
Retrospective 4,396 hospitalized patients in Italy showing significantly lower mortality with HCQ treatment, and identifying greater efficacy for a subgroup of patients in clustering analysis.
Jan 2021, J. Healthcare Engineering, https://www.hindawi.com/journals/jhe/2021/5556207/, https://c19p.org/dicastelnuovo2
Retrospective 3,729 rheumatic disease patients showing lower risk of mortality with HCQ/CQ use (HCQ/CQ vs. no DMARD therapy).
Jan 2021, Annals of the Rheumatic Diseases, https://ard.bmj.com/content/80/7/930, https://c19p.org/strangfeld
47% lower mortality with HCQ/CQ. Retrospective 1,271 patients with lung disease in Canada, China, Cuba, Ecuador, Germany, Italy and Spain, 83% treated with HCQ/CQ. Multivariable Cox regression HCQ/CQ mortality hazard ratio HR 0.53, p < 0.001.
Dec 2020, Archivos de Bronconeumología, https://www.sciencedirect.com/science/article/pii/S0300289620305354, https://c19p.org/signescosta
Small prophylaxis study of 208 healthcare workers in Turkey, 138 with high risk exposure received HCQ, while 70 with low and medium risk exposure did not. COVID-19 cases were lower in the treatment group, relative risk RR 0.43, p = 0.026. Since the control group had lower risk, the actual benefit may be larger.
Sep 2020, Medical J. Bakirkoy, 280-6, https://cms.galenos.com.tr/Uploads/Article_47752/BTD-16-280-En.pdf, https://c19p.org/polat
2075 hospital patients in Spain showing HCQ reduces mortality 52%, odds ratio OR 0.39, p<0.001, after adjustment for age, gender, temperature > 37 °C, and saturation of oxygen < 90% treatment with azithromycin, steroids, heparin, tocilizumab, a combination of lopinavir with ritonavir, and oseltamivir, and date of admission (model 4).
Sep 2020, Internal and Emergency Medicine, https://link.springer.com/article/10.1007/s11739-020-02505-x, https://c19p.org/ayerbe
Retrospective 890 cancer patients with COVID-19, adjusted mortality HR for HCQ/CQ 0.41, p<0.0001. Confirmed SARS-CoV-2 infection was required, which may help focus on more severe cases. Analysis with Cox proportional hazard model. Potential unmeasured confounders.
Aug 2020, Cancer Discovery, https://cancerdiscovery.aacrjournals.org/content/early/2020/08/18/2159-8290.CD-20-0773, https://c19p.org/pinato
Retrospective of 132 hospitalized patients. HCQ+AZ(52)/AZ(28) significantly reduced death/ICU, HR=0.45, p=0.04. Adjusted for Charlson Comorbidity Index (including age), obesity, O2, lymphocyte count, and treatments. Mean delay from admission to treatment 0.7 days.
Aug 2020, Int. J. Antimicrobial Agents, 2020, https://www.sciencedirect.com/science/article/pii/S0924857920303125, https://c19p.org/davido
HCQ decreases mortality from 26.4% to 13.5% (HCQ) or 20.1% (HCQ+AZ). Propensity matched HCQ HR 0.487, p=0.009. Michigan 2,541 patients retrospective. Before propensity matching the HCQ group average age is 5 years younger and the percentage of male patients is 4% higher which is likely to favor the treatment and the control respectively in the before-propensity matching results. Some reported limtiations of this study are inaccurate [ijidonline.com]. Corticosteroids were controlled for in the multivariate and propensity analyses as were age and comorbidities including cardiac disease and severity of illness. Age was an independent risk factor associated with mortality. HCQ was independently associated with decreased mortality, distinct from the steroid effect. 91% of all patients began treatment within two days of admission. HCQ was used throughout the study period, limiting time bias. Patients assigned to HCQ group had moderate and severe illness at presentation, which would favor..
Jun 2020, Int. J. Infectious Diseases, https://www.ijidonline.com/article/S1201-9712(20)30534-8/fulltext, https://c19p.org/arshad
HCQ decreases mortality, HR 0.53 (CI 0.41–0.67). IPTW adjustment does not significantly change HR 0.53 (0.41-0.68). Retrospective 6,000 patients in New York City.
Jun 2020, J. Gen. Intern. Med., https://link.springer.com/article/10.1007/s11606-020-05983-z, https://c19p.org/mikami
Chronic treatment with HCQ provides protection against COVID, odds ratio 0.51 (0.37-0.70). The actual benefit is likely to be larger becasue research shows that the risk of COVID-19 for systemic autoimmune disease patients is much higher overall. Ferri et al. show OR 4.42, p<0.001 [Ferri], which is the observed real-world risk, taking into account factors such as these patients potentially being more careful to avoid exposure.
Jun 2020, J. Medical Virology, https://onlinelibrary.wiley.com/doi/full/10.1002/jmv.26286, https://c19p.org/ferreira
Early treatment leads to significantly better clinical outcome and faster viral load reduction. Matched sample mortality HR 0.41 p-value 0.048. Retrospective 3,737 patients. This study includes both outpatients and hospitalized patients.
Jun 2020, Travel Medicine and Infectious Disease, https://www.sciencedirect.com/science/article/pii/S1477893920302817, https://c19p.org/lagier
Analysis of 868 patients on renal replacement therapy. Statistically significant reduction in mortality with HCQ for patients on dialysis (OR 0.47, p=0.005). No statistically significant change was found for transplant patients (the result is not given but likely the sample size is too small - the number of transplant patients was half the number of dialysis patients).
Apr 2020, Nefrología, https://www.sciencedirect.com/science/article/pii/S201325142030050X, https://c19p.org/sanchezalvarez
636 patients. HCQ+AZ reduced hospitalization 79% when used within 7 days (65% overall). Non-randomized.
Apr 2020, Prevent Senior Institute, São Paulo, Brazil, https://pgibertie.com/wp-content/uploads/2020/04/2020.04.15-journal-manuscript-final.pdf, https://c19p.org/esper
Small trial of low dose HCQ for healthcare workers with mild SARS-CoV-2 showing 68% lower progression to pneumonia, p = 0.21, and faster, but not statistically significant viral clearance. There were no ICU admissions or deaths. Prospective non-randomized study. The figures and supplementary data are not currently available in the pre-proof edition.
Dec 2020, Enfermedades Infecciosas y Microbiología Clínica, https://www.sciencedirect.com/science/article/abs/pii/S0213005X20304134, https://c19p.org/agusti
Observational prospective 254 hospitalized patients, HCQ+AZ mortality odds ratio OR 0.36, p = 0.04. Ventilation OR 0.20, p = 0.008.
Sep 2020, IJC Heart & Vasculature, https://www.sciencedirect.com/science/article/pii/S2352906720303365, https://c19p.org/heberto
HCQ was significantly associated with reduction / elimination of viral load, which was enhanced with AZ. Updated 8/13: responses to this paper have raised methodological issues [sciencedirect.com, sciencedirect.com, sciencedirect.com]. Despite the limitations, this early observational study was a milestone in the discovery process, including detailed daily evolution of PCR positivity. This study should be viewed in the context of the series of studies from this group. An update to this paper, including originally excluded patients, confirms the effectiveness of HCQ+AZ on viral clearance and early discharge [sciencedirect.com]. Also see [sciencedirect.com] and the response from the authors [sciencedirect.com].
Mar 2020, Int. J. Antimicrobial Agents, https://www.sciencedirect.com/science/article/abs/pii/S0924857920300996, https://c19p.org/gautretjaa
Retrospective 456 patients in Burkina Faso showing lower risk of ARDS (p=0.001) and mortality (p=0.38) with HCQ.
Feb 2021, Revue des Maladies Respiratoires, https://www.sciencedirect.com/science/article/pii/S0761842521000383, https://c19p.org/ouedraogo
Low dose prospective PEP study with 132 HCQ patients and 185 control patients, showing significantly lower COVID-19 cases with treatment. There were no serious adverse events. HCQ 800mg on day one followed by 400mg once weekly for 3 weeks.
Nov 2020, Int. J. Antimicrobial Agents, https://www.sciencedirect.com/science/article/pii/S0924857920304350, https://c19p.org/dhibar
RCT 320 patients in Thailand, showing significantly lower progression with HCQ for moderate/severe patients, and faster viral clearance with mild patients (statistically significant for 800mg). There are two sets of results - for moderate/severe patients, and for mild patients. There was no mortality for mild patients. NCT04303299.
Oct 2021, SSRN Electronic J., https://papers.ssrn.com/sol3/papers.cfm?abstract_id=3936499, https://c19p.org/atipornwanich
Study of SARS-CoV-2-IgG antibodies in 1122 health care workers in India finding 87% lower positives for adequate HCQ prophylaxis, 1.3% HCQ versus 12.3% for no HCQ prophylaxis. Adequate prophylaxis is defined as 400mg 1/wk for >6 weeks.
Oct 2020, SSRN, https://papers.ssrn.com/sol3/papers.cfm?abstract_id=3689618, https://c19p.org/goenka
Small RCT of nasopharyngeal viral load not showing significant differences. The rate of reduction for HCQ was 0.24 [0.03-0.46] RNA copies/mL/24h, and 0.14 [-0.10-0.37] for the control group (71% faster with HCQ but not statistically significant with the small sample size of 27 HCQ and 26 control patients). Analysis only over 96 hours. NCT04316377.
Jul 2020, Nature Communications, https://www.nature.com/articles/s41467-020-19056-6, https://c19p.org/lyngbakken
HCQ reduced cases from 38% to 7%. 106 people. No serious adverse effects.
Jun 2020, medRxiv, https://www.medrxiv.org/content/10.1101/2020.06.09.20116806v1, https://c19p.org/bhattacharya
197 patients. CQ effective. Day 10 viral RNA negative 91.4% HCQ versus 57.4% control. Median time to negative test 3 days versus 9 days for control.
Mar 2020, Zhong Nanshan, https://twitter.com/JamesTodaroMD/status/1243260720944480265, https://c19p.org/zhong2
Retrospective 1,915 rheumatic disease patients with COVID-19 in Argentina, showing lower mortality, severe oxygen requirement, and hospitalization with CQ/HCQ (antimalarial) use in unadjusted results, statistically significant only for severe oxygen requirement.
Oct 2022, Clinical Rheumatology, https://link.springer.com/10.1007/s10067-022-06393-8, https://c19p.org/isnardi
RCT 194 mild/asymptomatic low-risk patients in Cameroon, 97 treated with HCQ+AZ and 97 treated with doxycycline, showing 2.1% symptomatic patients at day 10 with HCQ+AZ, versus 4.3% with doxycycline, without statistical significance. There were only 6 patients with symptoms at day 10. There was no mortality or hospitalization, and no major adverse events.
Jul 2021, Cureus, https://www.cureus.com/articles/179159-doxycycline-vs-hydroxychloroquine--azithromycin-in-the-management-of-covid-19-patients-an-open-label-randomized-clinical-trial-in-sub-saharan-africa-doxycov, https://c19p.org/sobngwi
Early terminated late stage (8 days from onset, 59% on oxygen) RCT not showing statistically significant differences. NNF20SA0062834.
Jun 2021, European Respiratory J., https://erj.ersjournals.com/content/early/2021/05/28/13993003.00752-2021.article-info, https://c19p.org/sivapalan
Low risk patient RCT for HCQ+AZ and HCQ vs. control, not showing any significant differences. Authors note that the results are not applicable to higher risk patients, that positive PCR may simply reflect detection of inactive (non-infectious) viral remnants, that an alternative dosage regimen may be more effective, and that medication adherence was unknown. HCQ dosing was 600mg/day for 1 week, therapeutic levels may not be reached for several days. There were no deaths or serious adverse events. Viral load was already very high at baseline.
Nov 2020, eClinicalMedicine, https://www.sciencedirect.com/science/article/pii/S2589537020303898, https://c19p.org/omrani
Retrospective 683 patients in a rheumatology department, 384 chronic HCQ users and 299 control patients, showing no mortality for HCQ users vs. 2 deaths in the control group, and significantly fewer cases for HCQ users.
May 2021, Authorea, https://www.authorea.com/doi/full/10.22541/au.162257516.68665404, https://c19p.org/korkmaz
PSM retrospective SLE/RA patients in the USA, showing lower COVID-19 cases with HCQ prophylaxis.
Jun 2023, Studies in Health Technology and Informatics, https://ebooks.iospress.nl/doi/10.3233/SHTI230489, https://c19p.org/finkelstein
Retrospective 848 ICU patients in Saudi Arabia, showing lower mortality with HCQ in unadjusted results.
May 2023, Clinical Infection in Practice, https://www.sciencedirect.com/science/article/pii/S2590170223000122, https://c19p.org/alqadheeb
Prospective study of 9,058 COVID-19 ICU patients in Romania, showing lower mortality with HCQ treatment.
Nov 2022, European J. Anaesthesiology, https://journals.lww.com/10.1097/EJA.0000000000001776, https://c19p.org/bubenekturconi
Retrospective 759 hospitalized patients in the USA, showing lower mortality with combined HCQ+AZ+methylprednisolone treatment compared to methylprednisolone monotherapy.
Sep 2022, Frontiers in Pharmacology, https://www.frontiersin.org/articles/10.3389/fphar.2022.935370/full, https://c19p.org/go2
Retrospective 4,631 hospitalized patients in New York, showing higher mortality with remdesivir, and lower mortality with HCQ. Authors suggest that increased mortality during the first epidemic wave was partly due to strain on hospital resources.
Aug 2022, Open Forum Infectious Diseases, https://academic.oup.com/ofid/advance-article/doi/10.1093/ofid/ofac436/6675651, https://c19p.org/bowen
Retrospective 2,224 healthcare workers in India, showing lower risk of seropositivity with HCQ prophylaxis, without statistical significance.
Jul 2022, Indian J. Community Medicine, http://www.ijcm.org.in/text.asp?2022/47/2/202/350357, https://c19p.org/yadav4
Retrospective 580 hospitalized COVID+ patients in Cameroon, showing lower mortality with HCQ+AZ treatment.
Mar 2022, Travel Medicine and Infectious Disease, https://www.sciencedirect.com/science/article/pii/S1477893922000382, https://c19p.org/ebongue
Retrospective 14,921 hospitalized patients in Spain, showing lower mortality with HCQ treatment.
Jan 2022, PLOS ONE, https://journals.plos.org/plosone/article?id=10.1371/journal.pone.0261711, https://c19p.org/lavillaolleros
HCQ prophylaxis RCT with 201 weekly HCQ patients, 197 daily HCQ patients, and 200 control patients, concluding the prophylaxis is safe. There were no grade 3 or 4 AEs, SAEs, ER visits, or hospitalizations. There was only 4 confirmed cases, 2 in the placebo arm and one in each HCQ arm. 60% of patients had exposure at baseline. HCQ 400mg weekly or HCQ 200mg daily after a loading dose of 400mg on day 1.
Dec 2021, Int. J. Infectious Diseases, https://www.sciencedirect.com/science/article/pii/S1201971221012431, https://c19p.org/mckinnon
RCT 111 patients in India in 5 groups: severe patients: a) standard treatment, b) hydroxychloroquine + ribavirin + standard treatment, or c) lopinavir + ritonavir + ribavirin + standard treatment, and non-severe: a) standard treatment or b) hydroxychloroquine + ribavirin. Non-severe patients were transferred to the severe group on progression.
Sep 2021, Clinical Pharmacology: Advances and Applications, https://www.dovepress.com/antiviral-combination-clinically-better-than-standard-therapy-in-sever-peer-reviewed-fulltext-article-CPAA, https://c19p.org/panda2
HCQ prophylaxis RCT reporting statistically significant lower cases when pooling results with the COVID PREP RCT, OR 0.74 [0.55-1.0] p = 0.046. There were no significant safety issues. The trials were both terminated early resulting in a loss of power, however the combination shows statistically significant efficacy of HCQ. Note that this result has been censored in the journal version, see [medrxiv.org]. The journal paper still shows the COVID PREP paper in the reference list, but the analysis and discussion has been deleted. The journal version falsely states: "The prophylactic use of HCQ by HCW was safe but not effective", whereas the paper actually estimates OR 0.75, which becomes statistically significant OR 0.74 when pooled with COVID PREP. The preprint contains a different version: "...but did not produce a clinically useful treatment". It's unclear why ~25% fewer cases would not be useful. They also state "This is one of several negative studies"..
Aug 2021, Int. J. Infectious Diseases, https://www.sciencedirect.com/science/article/pii/S120197122300019X, https://c19p.org/naggie
Retrospective 926 patients in Senegal, 674 treated with HCQ+AZ, showing significantly higher hospital discharge at day 15 with treatment.
Jun 2021, J. Clinical Medicine, https://www.mdpi.com/2077-0383/10/13/2954, https://c19p.org/taieb
Retrospective 2,011 hospitalized patients in France, median age 67, showing lower mortality with HCQ+AZ, and further benefit with the addition of zinc.
Jun 2021, Therapeutics and Clinical Risk Management, https://www.dovepress.com/outcomes-of-2111-covid-19-hospitalized-patients-treated-with-hydroxych-peer-reviewed-fulltext-article-TCRM, https://c19p.org/lagier2
Retrospective 1,538 hospitalized patients in Italy, showing only HCQ associated with reduced mortality. Authors analyze mortality amongst those that were alive at day 7 to avoid survival time bias due to drug recording requiring a minimum of 5 days treatment.
Apr 2021, J. Clinical Medicine, https://www.mdpi.com/2077-0383/10/9/1951, https://c19p.org/derosa
Retrospective 47 rheumatic disease patients not finding significant differences with HCQ.
Apr 2021, Rheumatology Int. , https://link.springer.com/article/10.1007/s00296-021-04857-9, https://c19p.org/alzahrani
Retrospective case control study of 3,100 healthcare workers in India showing lower cases with HCQ prophylaxis, and an inverse association between the number of HCQ doses taken and the risk of COVID-19 cases. Low risk population with no mortality and no severe cases.
Mar 2021, Transactions of The Royal Society of Tropical Medicine and Hygiene, https://academic.oup.com/trstmh/advance-article/doi/10.1093/trstmh/trab047/6186057, https://c19p.org/dev
Retrospective 1,747 ICU patients in Belgium showing lower mortality with HCQ, multivariate mixed effects analysis HCQ aOR 0.64 [0.45-0.92].
Dec 2020, The Lancet Regional Health - Europe, https://www.sciencedirect.com/science/article/pii/S2666776220300193, https://c19p.org/taccone
Retrospective 333 patients in China, with only 8 HCQ patients, showing shorter duration of hospitalization with HCQ.
Dec 2020, Virus Research, https://www.sciencedirect.com/science/article/abs/pii/S0168170220311692, https://c19p.org/tan2
Retrospective 319 hospitalized patients in Belgium showing significantly lower mortality with HCQ.
Nov 2020, BMC Infectious Diseases, https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7691970/, https://c19p.org/vanhalem
64% lower hospitalization with HCQ. Retrospective 717 patients in Brazil with early treatment, adjusted OR 0.32, p=0.00081, for HCQ versus no medication, and OR 0.45, p=0.0065, for HCQ vs. anything else.
Oct 2020, Travel Medicine and Infectious Disease, https://www.sciencedirect.com/science/article/abs/pii/S1477893920304026, https://c19p.org/fonseca
Observational study 1,064 hospitalized patients in the Netherlands, 53% reduced risk of transfer to the ICU for mechanical ventilation with HCQ treatment starting on the first day of admission. Weighted propensity score adjusted hazard ratio for transfer to the ICU with HCQ treatment, HR = 0.47, p = 0.008. For CQ, HR = 0.8, p = 0.207. Mortality results in this study are only for mortality before transfer to the ICU. The combined ICU/death HR was 0.68, p = 0.024 for HCQ, and 0.85, p = 0.224 for CQ. Observational, multicenter, cohort study of hospitalized COVID-19 patients. 189 HCQ patients, 377 CQ, 498 control.
Sep 2020, Int. J. Infectious Diseases, https://www.sciencedirect.com/science/article/pii/S1201971220321755, https://c19p.org/lammers
Retrospective 307 hospital patients in Ghana showing 33% reduction in hospitalization time with HCQ, 29% reduction with HCQ+AZ, and 37% reduction with CQ+AZ.
Sep 2020, Pan African Medical J., https://www.panafrican-med-journal.com/content/series/37/1/9/full/, https://c19p.org/ashinyo
Retrospective 3,451 hospitalized patients, 30% reduction in mortality with HCQ after propensity adjustment, HR 0.70 [0.59 - 0.84].
Aug 2020, European J. Internal Medicine, https://www.sciencedirect.com/science/article/abs/pii/S0953620520303356, https://c19p.org/dicastelnuovo
Retrospective 8,075 hospitalized patients, 4,542 low-dose HCQ, 3,533 control. 35% lower mortality for HCQ (17.7% vs. 27.1%), adjusted HR 0.68 [0.62–0.76]. Low-dose HCQ monotherapy was independently associated with lower mortality in hospitalized patients. Patients exposed to others therapies (TCZ, AZ, LPV/RTV) were excluded. Statistical analysis was performed by an independent group. Calendar time of prescription and immortal time bias was taken into account. Corticosteroids prescriptions was low in both groups.
Aug 2020, Int. J. Antimicrobial Agents, https://www.sciencedirect.com/science/article/abs/pii/S0924857920303423, https://c19p.org/catteau
33 patient HCQ late treatment RCT: 24% improved viral clearance (p=0.71).
2 very small studies with hospitalized patients in Taiwan. RCT with 21 treatment and 12 SOC patients. No mortality, or serious adverse effects. Median time to negative RNA 5 days versus 10 days SOC, p=0.4. Risk of PCR+ at day 14, RR 0.76, p = 0.71. Small retrospective study with 12 of 28 HCQ patients and 5 of 9 in the control group being PCR- at day 14, RR 1.29, p = 0.7. The RCT and retrospective study are listed separately [Chen, Chen].
Jul 2020, PLoS ONE, https://journals.plos.org/plosone/article?id=10.1371/journal.pone.0242763, https://c19p.org/chen25
150 patient very late stage RCT showing no significant difference. Treatment was very late, an average of 16.6 days after symptom onset. Data favorable to HCQ was deleted in the second version, see analysis [mediterranee-infection.com]. "[HCQ] accelerate[s] the alleviation of clinical symptoms"; "More rapid alleviation of clinical symptoms with SOC plus HCQ than with SOC alone was observed during the second week since randomization"; "The efficacy of HCQ on the alleviation of symptoms, HR 8.83 [1.09-71.3], was more evident when the confounding effects of other anti-viral agents were removed".
Apr 2020, BMJ 2020, 369, https://www.bmj.com/content/369/bmj.m1849, https://c19p.org/tang
This paper has conflicting values, table S2 shows 12 control hospitalizations, while table 2 shows 11. The original report for this paper had more conflicting values, with values reported in Table 2 and the abstract corresponding to 12 control hospitalizations, while others corresponded to 11 control hospitalizations. The counts in table S2 also do not match - n=290 is given for secondary endpoints but the three groups add up to n=238. The sum of the secondary endpoint counts for the control group in table 2 do not match the group size. One missing patient may be the 12th control hospitalization but there are 2 more missing. There was a 16% reduction in hospitalization and 34% reduction in the risk of no symptom resolution, without statistical significance due to small samples. Treatment delay is unknown at this time. They report a delay of up to 120 hours after symptoms plus an additional unspecified delay where medication was provided to patients at the first home visit. Authors..
Jul 2020, Clinical Infectious Diseases, ciaa1009, https://academic.oup.com/cid/article/doi/10.1093/cid/ciaa1009/5872589, https://c19p.org/mitja
Prospective study of 187 telemedicine patients in Brazil. 74 presenting with moderate symptoms were offered treatment with HCQ+AZ, 12 did not accept HCQ (taking AZ only), forming a control group. There was lower hospitalization and improved recovery with treatment.
Nov 2021, Heliyon, https://www.sciencedirect.com/science/article/pii/S2405844023025446, https://c19p.org/chechter
Prospective study with 221 healthcare workers, showing lower risk of COVID-19 with HCQ prophylaxis.
Aug 2021, NCT04333225, https://clinicaltrials.gov/study/NCT04333225, https://c19p.org/mccullough4
Retrospective 213 hospitalized patients in Czech Republic showing lower mortality with HCQ. Subject to confounding by indication.
Dec 2020, medRxiv, https://www.medrxiv.org/content/10.1101/2020.12.03.20239863v1, https://c19p.org/modrak
Study of hospital health care workers showing HCQ prophylaxis reduces COVID-19 significantly, OR 0.30, p=0.02. 94 positive health care workers with a matched sample of 87 testing negative. Full course prophylaxis was important in this study which used a low dose of 400mg/week HCQ (800mg for week 1), so it may take longer to reach therapeutic levels. Actual benefit of HCQ may be larger because severity of symptoms are not considered here but HCQ may also reduce severity.
Jul 2020, medRxiv, https://www.medrxiv.org/content/10.1101/2020.07.21.20159301v1, https://c19p.org/khurana
166 patients hospitalised with COVID-19, HCQ increased survival 1.4 - 1.8 times when patients admitted in early stages. Early is relative to hospital admission here - all patients were in relatively serious condition.
May 2020, Preprints, https://www.preprints.org/manuscript/202005.0057, https://c19p.org/membrillo
PrEP RCT showing lower cases with HCQ prophylaxis. The trial was halted after 47% enrollment, p < 0.05 would be reached at ~75% enrollment if similar results continued. HR 0.66/0.68 for full medication adherence, 0.72/0.74, p = 0.18/0.22 overall (1x/2x dosing). Efficacy for first responders was higher, OR 0.32, p = 0.01. First responders had a much higher incidence, allowing greater power, and reducing the effect of confounders such as misdiagnosis of other conditions or survey issues. Performance is similar to the control arm for the first 3 weeks. The effect may be greater with a dosage regimen that achieves therapeutic levels faster [tandfonline.com]. ~40% of participants suspected they might have had COVID-19 before the trial, the effect in people without prior COVID-19 may be higher. Research shows the treatment used in the control arm (folic acid) may have significant efficacy for COVID-19 [Deschasaux-Tanguy, Farag], so the true effectiveness of HCQ may be higher than observed...
Sep 2020, Clinical Infectious Diseases, https://academic.oup.com/cid/advance-article/doi/10.1093/cid/ciaa1571/5929230, https://c19p.org/rajasingham
Very small early terminated RCT in India, showing lower mortality but without statistical significance with the very small sample size. Time since symptom onset is not provided. The recovery percentage for non-severe group B (86.7%) does not match any number of recoveries, we have used the closest number (15/17).
Jun 2021, medRxiv, https://www.medrxiv.org/content/10.1101/2021.06.06.21258091v1, https://c19p.org/singh2
Retrospective 161 hospitalized patients in Saudi Arabia showing lower ventilation and ICU admission with HCQ, but not statistically significant with the small sample sizes.
Sep 2020, Saudi Pharmaceutical J., https://www.sciencedirect.com/science/article/pii/S1319016420302334, https://c19p.org/almazrou
Retrospective patients with rheumatologic conditions showing zero of 10,703 COVID-19 deaths for HCQ patients versus 7 of 21,406 propensity matched control patients (not statistically significant). The average age of HCQ patients is slightly lower 64.8 versus 65.4 control. COVID-19 cases OR 0.79, p=0.27. There are several significant differences in the propensity matched patients that could affect results, e.g., 20.9% SLE versus 24.7%.
Sep 2020, Lancet Rheumatology, https://www.thelancet.com/journals/lanrhe/article/PIIS2665-9913(20)30305-2/fulltext, https://c19p.org/gentry
840 patient HCQ late treatment study: 78% lower mortality (p<0.0001).
Retrospective 750 COVID-19 patients in Saudi Arabia, showing lower mortality with HCQ treatment in unadjusted results. Authors note that the poor results in some other trials may be related to increased dosages and later treatment.
Apr 2023, J. Multidisciplinary Healthcare, https://www.dovepress.com/profiles-of-independent-comorbidity-groups-in-senior-covid-19-patients-peer-reviewed-fulltext-article-JMDH, https://c19p.org/said2
Retrospective 80 consecutive pregnant patients with autoimmune rheumatic diseases in Qatar, showing lower risk of COVID-19 cases with HCQ prophylaxis.
Apr 2022, Cureus, https://www.cureus.com/articles/91696-characteristics-and-obstetric-outcomes-in-women-with-autoimmune-rheumatic-disease-during-the-covid-19-pandemic-in-qatar, https://c19p.org/satti
Retrospective 3,712 hospitalized patients in Egypt, showing lower mortality with HCQ treatment in unadjusted results. According to the official treatment protocol, HCQ was recommended with higher risk and/or more serious cases.
Jan 2022, PLOS ONE, https://journals.plos.org/plosone/article?id=10.1371/journal.pone.0262348, https://c19p.org/abdelghaffar
Analysis of 1255 COVID-19 patients in Wuhan Tongji Hospital finding 0.61% with systemic autoimmune diseases, much lower than authors expected (3%-10%). Authors hypothesise that protective factors, such as CQ/HCQ use, reduce hospitalization.
Jun 2020, Annals of the Rheumatic Diseases, https://ard.bmj.com/content/79/9/1163, https://c19p.org/huangard
Retrospecttive 220 COVID-19 patients with rheumatic disease in Japan, showing lower mortality and hospitalization with HCQ prophylaxis, without statistical significance.
Sep 2022, Modern Rheumatology, https://academic.oup.com/mr/advance-article/doi/10.1093/mr/roac104/6692611, https://c19p.org/oku
Retrospective 403 hospitalized patients in Spain, showing lower mortality with treatment, however authors do not adjust for the differences between the groups. Confounding by indication is likely.
May 2021, Archivos de Medicina Universitaria, https://digibug.ugr.es/handle/10481/69170, https://c19p.org/ramirezgarcia
3,885 patient HCQ late treatment study: 36% lower mortality (p=0.005).
Retrospective 352 hospitalized COVID-19 patients in Belgium and 3,533 control patients from the contemporaneous Belgian Collaborative Group, showing significantly lower mortality with HCQ treatment. The survival benefit was consistent in all age groups. No torsade de pointes or ventricular arrhythmias were observed. Mean time from onset is not provided, but 43% of patients with known onset were admitted within 5 days, making the efficacy consistent with expectations based on the treatment delay [c19hcq.org]. HCQ 800mg day one, 200mg bid for five days, according to national guidelines. Authors note that the poor results in SOLIDARITY/RECOVERY may be related to the excessively high doses used. Most patients also received AZ. Adjusted results are only provided for all HCQ patients. Publication was delayed over 3 years. Authors reported in 2021 that the paper had been rejected by the editors of four different journals, without peer review [twitter.com].
Sep 2023, New Microbes and New Infections, https://www.sciencedirect.com/science/article/pii/S2052297523000914, https://c19p.org/meeus
Small early terminated late treatment RCT comparing vitamin C + folic acid, HCQ + folic acid, and HCQ+AZ, showing non-statistically significantly lower hospitalization with HCQ/HCQ+AZ, and faster viral clearance with HCQ. Enrollment was a median of 5.9 days after onset (6.2 and 6.3 in the treatment arms). The median time to viral clearance for vitamin C + folic acid was 8 days in the preprint but changed to 7 days in the published paper without explanation. Both vitamin C [c19early.org] and folic acid [Deschasaux-Tanguy, Farag] show efficacy in other trials, so the true effectiveness of HCQ(+AZ) may be higher than observed. Low risk patients, median age 37, no deaths (not matching the title which claims "high risk"). There was a post hoc addition of a new cycle threshold that obscures the statistically significant faster clearance. There was no analysis for time from symptom onset. Authors identify (relatively) low and high risk cohorts, but do not provide either viral..
Dec 2020, eClinicalMedicine, https://www.thelancet.com/journals/eclinm/article/PIIS2589-5370(21)00053-5/fulltext, https://c19p.org/johnston
PSM retrospective 29 hospitals in Saudi Arabia, finding lower mortality with HCQ, without reaching statistical significance (described by authors as "no impact").
Feb 2023, Saudi Pharmaceutical J., https://www.sciencedirect.com/science/article/pii/S1319016423000348, https://c19p.org/alshamrani
Authors have not responded to a request for the data. Outpatient RCT with 687 HCQ and 682 control patients in Brazil, showing lower hospitalization with treatment, not reaching statistical significance. Higher efficacy was seen with treatment <4 days from onset, RR 0.61. The associated meta analysis includes mostly late treatment studies, for example in [Schwartz] the median delay from onset was 7 days. [Omrani] is missing. The values for [Johnston] are incorrect - the study shows 4 hospitalizations in the control arm - RR for this study should be 0.58 instead of 0.78.
Mar 2022, The Lancet Regional Health - Americas, https://www.sciencedirect.com/science/article/pii/S2667193X22000606, https://c19p.org/avezum
PSM retrospective 9,638 patients in the USA, showing significantly lower mortality with HCQ in early 2020 (1,157 HCQ patients), and no significant difference in late 2020 (82 HCQ patients). The few patients treated in the later period may be in more serious condition due to the effort required to overcome the politicization and censorship in the study country. Authors refer to their result as "no relevant benefit in mortality between the two surges".
Feb 2023, Research Square, https://www.researchsquare.com/article/rs-2596201/v1, https://c19p.org/delgado
Retrospective 1,276 hospitalized patients showing significantly faster viral clearance with HCQ. Authors also perform a meta-analysis of 9 studies, with 1,461 HCQ-treated patients and 958 controls, showing significantly faster viral clearance with HCQ on day 7.
Jul 2024, Acta Scientific Microbiology, https://actascientific.com/ASMI/pdf/ASMI-07-1413.pdf, https://c19p.org/brouqui4
Retrospective 1,787 hospitalized COVID-19 patients in the United Arab Emirates, identifying hydroxychloroquine as reducing the risk of ICU admission in a machine learning model. Only unadjusted quantitative results are provided, which also show a benefit.
Jan 2024, PLOS ONE, https://journals.plos.org/plosone/article?id=10.1371/journal.pone.0291373, https://c19p.org/alshehhi
Retrospective 512 rheumatic disease patients in Iran, showing lower risk of COVID-19 with HCQ use.
Sep 2022, Reumatologia/Rheumatology, https://www.termedia.pl/doi/10.5114/reum.2022.119039, https://c19p.org/sahebari
Retrospective 26,121 cases and 2,369,020 controls ≥65yo in Canada, showing lower cases with chronic use of HCQ.
Mar 2022, Open Forum Infectious Diseases, https://academic.oup.com/ofid/advance-article/doi/10.1093/ofid/ofac156/6555707, https://c19p.org/macfadden
Retrospective type 1 diabetes patients in Saudi Arabia showing reduced risk of cases with HCQ prophylaxis.
Nov 2021, BioMed Research Int., https://www.hindawi.com/journals/bmri/2021/1676914/, https://c19p.org/ahmed2
PSM retrospective 144 alopecia patients in the USA, showing lower risk of COVID-19 with HCQ prophylaxis. The supplemental appendix is not available.
Jun 2021, J. Drugs in Dermatology, https://jddonline.com/articles/dermatology/S1545961621P0914X, https://c19p.org/shaw
605 hospitalized patients in Saudi Arabia showing no mortality with HCQ (only 6 patients received HCQ).
Mar 2021, Int. J. Infectious Diseases, https://www.sciencedirect.com/science/article/pii/S1201971221002769, https://c19p.org/barry
Retrospective 824 hospitalized patients in Turkey showing lower ICU admission for HCQ vs. favipiravir.
Dec 2020, J. Infection and Public Health, https://www.sciencedirect.com/science/article/pii/S1876034120307735, https://c19p.org/guner
Prospective observational study of 315 hospitalized patients in Italy showing 65% lower mortality with HCQ. The median treatment delay was 6 days for survivors and 6.5 days for non-survivors. Mortality relative risk: RR 0.35, p = 0.2, propensity score matched RR 0.75, p = 0.36, multivariate Cox regression RR 0.43, p < 0.001, univariate Cox regression
Nov 2020, Open Forum Infectious Diseases, https://academic.oup.com/ofid/advance-article/doi/10.1093/ofid/ofaa563/5992463, https://c19p.org/falcone
Retrospective 258 hospitalized patients in Italy showing lower mortality with HCQ treatment, unadjusted relative risk RR 0.455, p<0.001. Data is in the supplementary appendix.
Nov 2020, Bioscience Reports, https://portlandpress.com/bioscirep/article/doi/10.1042/BSR20203455/226985, https://c19p.org/boari
67% lower mortality with HCQ. Retrospective 416 elderly patients in Spain showing adjusted HCQ mortality hazard ratio HR 0.33, p = 0.1.
Nov 2020, Revista Española de Geriatría y Gerontología, https://www.sciencedirect.com/science/article/pii/S0211139X20301748, https://c19p.org/aguilagordo
Retrospective 652 transplant recipient patients in Spain showing 46% lower mortality for patients treated with HCQ, unadjusted relative risk RR 0.54, p<0.0001.
Oct 2020, American J. Transplantation, https://onlinelibrary.wiley.com/doi/abs/10.1111/ajt.16369, https://c19p.org/coll
Small PrEP RCT showing that PrEP with HCQ is safe at the dosage used. There were no deaths, hospitalizations, or serious adverse events. The paper states: "Among all trial participants at the end of the first month (n=253), only one participant from the placebo arm (1/116, 0.8%), tested positive for SARS-CoV-2 PCR and for a SARS-CoV-2 serology test". The abstract states: "only one participant in each group was diagnosed with COVID-19".
Sep 2020, Trials, https://trialsjournal.biomedcentral.com/articles/10.1186/s13063-021-05758-9, https://c19p.org/graupujol
Retrospective 4035 hospitalized patients in Spain showing reduced mortality with HCQ (data is in the supplementary appendix).
Aug 2020, Clinical Microbiology and Infection, https://www.clinicalmicrobiologyandinfection.com/article/S1198-743X(20)30431-6/fulltext, https://c19p.org/berenguer
Viral load comparison for 34 HCQ and 32 control patients hospitalized with moderate COVID-19. All patients recovered limiting the room for beneficial effects. While not achieving statistical significance, results show faster recovery with HCQ. The greatest benefit is seen mid-recovery as expected for an effective treatment: Δt7-12: 81% improvement with HCQ Δt<7: 24% improvement with HCQ For Δt>12, everyone has recovered so there is no room for improvement. Since the HCQ group started slightly higher the improvement is slightly less. Most participants have also dropped out by this test, with only 6 HCQ and 9 control remaining (also suggesting HCQ patients recovered faster).
Jun 2020, Braz J Microbiol, https://link.springer.com/article/10.1007/s42770-020-00395-x, https://c19p.org/faicofilho
Prospective study of 64 rheumatic disease patients with COVID-19, showing no significant difference in outcomes with HCQ use.
Feb 2023, Rheumatology Advances in Practice, https://academic.oup.com/rheumap/advance-article/doi/10.1093/rap/rkad025/7059537, https://c19p.org/mathew
Retrospective 34 rheumatological disease patients with COVID-19 in Saudi Arabia, showing lower risk of severe cases with HCQ use in unadjusted results, without statistical significance.
May 2023, J. Medicine and Life, https://europepmc.org/article/PMC/PMC10478665, https://c19p.org/alqatari
Small prophylaxis study with 130 healthcare workers in the USA, showing lower symptomatic cases with HCQ prophylaxis, without statistical significance. HCQ participants were significantly older. The only symptomatic HCQ patient reported headache only as a potential COVID-19 symptom.
Jul 2022, medRxiv, https://www.medrxiv.org/content/10.1101/2022.07.01.22277058, https://c19p.org/raabe
Retrospective 744 hospitalized patients in Thailand, showing lower risk of a poor outcome for favipiravir treatment within 4 days of symptom onset. Early treatment with CQ/HCQ and lopinavir/ritonavir or darunavir/ritonavir also showed lower risk, but without statistical significance. Sample sizes for the number of patients treated within 4 days of symptom onset are not provided.
Sep 2021, Southeast Asian J. Tropical Medicine and Public Health, https://journal.seameotropmednetwork.org/index.php/jtropmed/article/view/490, https://c19p.org/sawanpanyalert
208 patient HCQ late treatment study: 44% lower mortality (p=0.14) and 3% improved recovery (p=0.91).
Retrospective 208 hospitalized COVID-19 patients in Burkina Faso showing lower mortality with HCQ/CQ+AZ treatment, without statistical significance. There was no difference for recovery.
Feb 2021, J. Infectious Diseases and Epidemiology, https://www.clinmedjournals.org/articles/jide/journal-of-infectious-diseases-and-epidemiology-jide-7-192.php?jid=jide, https://c19p.org/baguiya
33% lower mortality with HCQ+AZ, p=0.28. Retrospective 122 French dialysis patients. 69% lower combined mortality/ICU, p=0.11, for the subgroup not requiring O2 on diagnosis (slightly earlier treatment).
Oct 2020, Clinical Kidney J., October 2020, 878–888, https://academic.oup.com/ckj/article/13/5/878/5934808, https://c19p.org/lano
Retrospective 766 hospitalized patients in DRC showing mortality reduced from 29% to 11%, and improvement at 30 days increased from 65% to 84%. Mortality cox regression adjusted hazard ratio aHR 0.26, p < 0.001 Risk of no improvement adjusted odds ratio aOR 0.28, p < 0.001 Using marginal structural model analysis these risks became: Mortality MSM adjusted odds ratio aOR 0.65, p = 0.166 Risk of no improvement MSM adjusted odds ratio aOR = 0.65, p = 0.132 Median age 46, 630 treated with CQ+AZ.
Oct 2020, The American J. Tropical Medicine and Hygiene, https://www.ajtmh.org/content/journals/10.4269/ajtmh.20-1240, https://c19p.org/nachega
Prospective 56 patients in Uganda, 29 HCQ and 27 control, showing 25.6% faster recovery with HCQ, 6.4 vs. 8.6 days (p = 0.20). There was no ICU admission, mechanical ventilation, or death. Treatment delay is not specified but at least a portion of patients appear to have been treated early.
Sep 2020, BMJ Open Respiratory Research, https://bmjopenrespres.bmj.com/content/7/1/e000646, https://c19p.org/kirenga
Small 105 patient RCT in Uganda showing no significant differences. No mortality was reported. The patients were very young (median age 32), recovering in a median time of 3 days with standard of care, so there is little room for a treatment to make improvements. Time since symptom onset is not specified, but the distribution of symptoms at baseline suggests that the enrollment is relatively late within a cohort of low risk patients.
Jun 2021, Research Square, https://www.researchsquare.com/article/rs-506195/v1, https://c19p.org/byakikakibwika
Retrospective 976 hospitalized patients with 834 treated with HCQ+AZ showing HCQ mortality relative risk RR 0.35, p < 0.0001. Note that in this case HCQ was recommended for mild/moderate cases, so more severe cases may not have received HCQ (which may also be why they became severe cases). We note that this is opposite to a common bias in HCQ studies - in many cases HCQ was more likely to be given to more severe cases.
Nov 2020, medRxiv, https://www.medrxiv.org/content/10.1101/2020.11.16.20232223v1, https://c19p.org/budhiraja
Retrospective 654 hospitalized patients focused on low-density lipoprotein cholesterol levels, also showing results for HCQ with 605 HCQ patients, unadjusted 30 day mortality relative risk RR 0.37, p = 0.008.
Oct 2020, medRxiv, https://www.medrxiv.org/content/10.1101/2020.10.06.20207092v1, https://c19p.org/aparisi
Prospective study of HCQ prophylaxis in the USA, with 56 HCQ patients and 24 control patients, showing no significant differences. NCT04354870
Oct 2021, ClinicalTrials.gov, NCT04354870, https://clinicaltrials.gov/ct2/show/results/NCT04354870, https://c19p.org/belmont
Small prophylaxis trial with 29 low dose HCQ and 455 control healthcare workers in India, showing no statistically significant differences.
Sep 2021, medRxiv, https://www.medrxiv.org/content/10.1101/2021.09.13.21262971v1, https://c19p.org/agarwal2
Retrospective 125 pregnant women hospitalized with COVID-19 in Turkey, showing no significant difference in hospitalization length with HCQ, and longer hospitalization with lopinavir/ritonavir use.
Jul 2024, J. Controversies in Obstetrics & Gynecology and Pediatrics, http://journal-jcogp.com/Publication/DisplayArticle/27358, https://c19p.org/degirmencih
Retrospective 103 SLE and 524 RA patients in Italy, showing significantly lower mortality/ventilation with HCQ use for SLE patients, and no significant difference for RA patients in unadjusted results. Authors did not include HCQ in multivariable analysis, only including four variables "chosen among the most clinically relevant". Multivariable analysis may significantly improve results for RA patients because HCQ use may correlate with more severe disease due to use for patients that failed or do not tolerate first-line therapies. It is not clear how the patients were selected - the very high ~25% ventilation/mortality suggests that most were hospitalized COVID-19 patients, in which case any benefit of HCQ in reducing hospitalizations will not be reflected in the results. Authors falsely state that "subsequent studies have definitely proved that [HCQ] is not linked to COVID-19 prognosis", suggesting significant bias, and possibily indicating why HCQ..
Oct 2023, Lupus Science & Medicine, https://lupus.bmj.com/lookup/doi/10.1136/lupus-2023-000945, https://c19p.org/scirocco
Retrospective 755 autoimmune rheumatic disease patients, showing lower risk of PASC (long COVID) with HCQ use, without statistical significance.
Apr 2023, The Lancet Rheumatology, https://www.sciencedirect.com/science/article/pii/S2665991323000668, https://c19p.org/sen2
Case control study with 2,431 hospitalized COVID-19 patients in India, showing lower mortality with HCQ treatment, without statistical significance.
Apr 2023, The American J. Tropical Medicine and Hygiene, https://www.ajtmh.org/view/journals/tpmd/108/4/article-p727.xml, https://c19p.org/krishnan2
Retrospective 149 patients under invasive mechanical ventilation in Germany showing no significant difference in mortality with HCQ in unadjusted results.
Mar 2023, Scientific Reports, https://www.nature.com/articles/s41598-023-31944-7, https://c19p.org/aweimerh
Retrospective 1,213 rheumatic disease patients in France, showing lower risk of mortality and severe cases with HCQ use in univariate analysis, without statistical significance.
Mar 2023, Frontiers in Medicine, https://www.frontiersin.org/articles/10.3389/fmed.2023.1152587/full, https://c19p.org/chevalier
Retrospective 81 cases and 396 controls among rheumatic disease patients in the Netherlands, showing lower risk of hospitalization with HCQ prophylaxis, without statistical significance.
Feb 2022, Clinical Pharmacology & Therapeutics, https://ascpt.onlinelibrary.wiley.com/doi/10.1002/cpt.2551, https://c19p.org/opdam
Retrospective 2,533 SLE patients in Denmark showing no significant difference in hospitalization risk for COVID-19 cases with HCQ treatment.
Aug 2021, J. Clinical Medicine, https://www.mdpi.com/2077-0383/10/17/3842, https://c19p.org/cordtz2
Small RCT comparing HCQ and CQ in China with 88 very late stage (17.6 days from onset to hospitalization and ~10 days to randomization) patients. The primary clinical outcomes (TTCR and TTCI) were not significantly different. Authors note that HCQ may have more promising efficacy in immune system modulation, indicated by ferritin reduction in the moderate cases and improvement of CT scores and lymphocyte counts in the severe cases. HCQ and CQ were well tolerated. Authors also compare RCT patients to a matched sample of non-RCT patients in the same hospital, showing shorter time to discharge with CQ/HCQ, but not statistically significant due to the small size.
Jan 2021, Science China Life Sciences, https://link.springer.com/article/10.1007/s11427-020-1871-4, https://c19p.org/li3
55% lower death with HCQ+AZ. Retrospective 160 hospitalized patients in the Democratic Republic of Congo, 92% receiving HCQ+AZ, showing adjusted OR 0.24 [0.03-2.2].
Dec 2020, PLoS ONE, https://journals.plos.org/plosone/article?id=10.1371/journal.pone.0244272, https://c19p.org/matangila
1,150 patient HCQ late treatment study: 44% lower mortality (p=0.14).
Retrospective 1210 hospitalized patients in Turkey focused on chronic kidney disease, haemodialysis and renal transplant patients, but also showing lower mortality with HCQ. Subject to confounding by indication.
Dec 2020, Nephrology Dialysis Transplantation, https://academic.oup.com/ndt/article/35/12/2083/6020341, https://c19p.org/ozturk
Small retrospective study of 22 lung cancer patients, 14 treated with HCQ+AZ, showing HCQ+AZ mortality relative risk RR 0.57, p = 0.145.
Sep 2020, Ann. Oncol., 2020, Sep, 31, S1026, https://www.annalsofoncology.org/article/S0923-7534(20)41826-5/fulltext, https://c19p.org/serrano
Observational prospective 108 hospitalized patients 65 and older, showing HCQ mortality OR 0.49, p = 0.15.
Jun 2020, Aging, 11306-11313, https://www.aging-us.com/article/103583/text, https://c19p.org/bousquet
Very small observational study of 15 dialysis patients showing HCQ mortality RR 0.50, p = 0.53.
Jun 2020, Clinical Kidney J., 334–339, https://academic.oup.com/ckj/article/13/3/334/5860798, https://c19p.org/fontana
Analysis of 94 hemodialysis COVID-19 positive patients, showing lower mortality with HCQ treatment, not reaching statistical significance.
May 2020, Kidney Int., 20-26, July 1, 2020, https://www.kidney-international.org/article/S0085-2538(20)30508-1/fulltext, https://c19p.org/alberici
Retrospective 3,473 hospitalized patients showing lower mortality with HCQ+zinc.
Oct 2020, Research Square, https://www.researchsquare.com/article/rs-94509/v1, https://c19p.org/frontera
Retrospective 393 hospitalized COVID-19 patients in Turkey, showing lower ICU admission and shorter hospitalization time with HCQ. There was no significant difference for mortality. Severity was higher in the HCQ group with greater baseline ventilation, high flow oxygen, fever, and dyspnea.
Jan 2022, The J. Infection in Developing Countries, https://jidc.org/index.php/journal/article/view/14933, https://c19p.org/omma
Prospective study of 9,212 autoimmune rheumatic disease patients showing lower mortality with HCQ, without reaching statistical significance. Authors incorrectly state "HCQ use did not influence occurrence of COVID-19 (RR = 0.909, CI (0.715,1.154), p = 0.432) or mortality (p = 0.097)" [nature.com]. CFR for the autoimmune rheumatic disease patients was 4.6 times higher than in the general population from the same area.
Aug 2021, Research Square, https://www.researchsquare.com/article/rs-805748/v1, https://c19p.org/patil
Retrospective study of 917,198 hospitalized COVID-19 cases covered by the Iran Health Insurance Organization over 26 months showing that antithrombotics, corticosteroids, and antivirals reduced mortality while diuretics, antibiotics, and antidiabetics increased it. Confounding makes some results very unreliable. For example, diuretics like furosemide are often used to treat fluid overload, which is more likely in ICU or advanced disease requiring aggressive fluid resuscitation. Hospitalization length has increased risk of significant confounding, for example longer hospitalization increases the chance of receiving a medication, and death may result in shorter hospitalization. Mortality results may be more reliable. Confounding by indication is likely to be significant for many medications. Authors adjustments have very limited severity information (admission type refers to ward vs. ER department on initial arrival). We can estimate the impact of confounding from typical usage..
Dec 2023, Frontiers in Public Health, https://www.frontiersin.org/articles/10.3389/fpubh.2023.1280434/full, https://c19p.org/mehrizi
Retrospective 615 hospitalized COVID-19 patients in Morocco, showing lower mortality with HCQ in unadjusted results.
Dec 2022, Cureus, https://www.cureus.com/articles/122896-predictive-factors-of-death-and-the-clinical-profile-of-hospitalized-covid-19-patients-in-morocco-a-one-year-mixed-cohort-study, https://c19p.org/charif
Retrospective 1,816 COVID-19 patients with atrial fibrillation in Spain, showing lower mortality with HCQ treatment.
Mar 2022, Medicina Clínica, https://www.sciencedirect.com/science/article/pii/S0025775322000549, https://c19p.org/azanagomez
Retrospective 197 hospitalized COVID-19 patients in Spain, showing lower progression to pneumonia with HCQ in unadjusted results.
Mar 2021, Advances in Laboratory Medicine / Avances en Medicina de Laboratorio, https://www.degruyter.com/document/doi/10.1515/almed-2021-0017/html, https://c19p.org/rubiosanchez
Retrospective 117 COVID-19 positive doctors in India showing lower mortality and severity with HCQ prophylaxis, without statistical significance in unadjusted results without group details. Results do not include the risk of positive cases.
Jun 2024, J. College of Medical Sciences-Nepal, https://www.nepjol.info/index.php/JCMSN/article/view/43302, https://c19p.org/dey2
Retrospective 11,468 vaccinated rheumatic disease patients in the USA, showing lower risk of COVID-19 with HCQ/CQ use compared with all other treatments. Adjusted results are only provided with respect to specific other treatments.
Jul 2022, medRxiv, https://www.medrxiv.org/content/10.1101/2022.07.13.22277606, https://c19p.org/patel4
Very late stage RCT with 214 patients, mean SpO2 65%, 162 on mechanical ventilation, showing no significant difference in mortality. Patients not intubated at baseline show greater improvement, HR 0.43 [0.09-2.03]. Table 4 shows different results to the abstract - table 4 adjusted HR 0.80 [0.51-1.23], abstract HR 0.88 [0.51-1.53]. There was no significant difference in severe adverse events.
Feb 2021, medRxiv, https://www.medrxiv.org/content/10.1101/2021.02.01.21250371v1, https://c19p.org/hernandezcardenas
HCQ HR 0.83 [0.77-0.89] based on propensity score matched retrospective analysis of 1,645 hospitalized patients. Prednisone HR 0.85 [0.82-0.88], 14 other medications showed either no signicant benefit or a negative effect.
Jul 2020, medRxiv, https://www.medrxiv.org/content/10.1101/2020.07.17.20155960v1, https://c19p.org/bernaola
Retrospective study of 77 outpatients with rheumatic diseases diagnosed with COVID-19, showing lower risk of severe COVID-19 with HCQ use in unadjusted results.
Dec 2023, Immunopathologia Persa, https://immunopathol.com/Article/ipp-40568, https://c19p.org/salesi
Retrospective 301 consecutive SLE patients with COVID-19, showing lower risk of severe outcomes with HCQ use, with statistical significance in multivariable adjusted model 1 but not model 2.
Feb 2024, Lupus, http://journals.sagepub.com/doi/10.1177/09612033241230736, https://c19p.org/liu18
Retrospective 432 autoimmune disease patients in China showing lower hospitalization with HCQ without statistical significance (OR 0.566, p=0.085) in unadjusted results, slightly higher COVID-19 cases without statistical significance, and increased cough compared with CNI.
Dec 2023, J. Translational Autoimmunity, https://www.sciencedirect.com/science/article/pii/S2589909023000400, https://c19p.org/huang7
Retrospective cohort of 6,145 SLE patients showing lower incidence of COVID-19 for patients receiving HCQ/CQ (antimalarials), without statistical significance. Groups were not matched and results may be influenced by factors such as disease severity. HCQ/antimalarials were used more in moderate/severe SLE patients, suggesting that the estimated protective effect will underestimate the real effect.
Nov 2023, BMJ Open, https://bmjopen.bmj.com/lookup/doi/10.1136/bmjopen-2022-071072, https://c19p.org/rabe
PSM retrospective 322 rheumatological patients on HCQ and 645 matched controls, showing lower risk of COVID-19 with treatment, without statistical significance. Authors mention lower mortality with HCQ but do not provide details. Only an abstract is available.
May 2023, J. Clinical Rheumatology, https://journals.lww.com/10.1097/RHU.0000000000001986, https://c19p.org/dulcey
Case control study of healthcare workers in India, showing lower risk of cases with HCQ prophylaxis, without statistical significance. While authors comment negatively, as may be required for publication, and this study alone is not statistically significant, the result is consistent with the positive results in all studies to date.
Nov 2022, F1000Research, https://f1000research.com/articles/11-1298/v1, https://c19p.org/sukumar
Retrospective 700 patients with autoimmune rheumatic disease in Qatar, showing lower risk of COVID-19 with HCQ use, without statistical significance. For patients having close contact with COVID-19 cases, there was a statistically significant association with HCQ use and lower risk of COVID-19 in unadjusted results.
Aug 2022, Qatar Medical J., https://www.qscience.com/content/journals/10.5339/qmj.2022.37, https://c19p.org/becetti
215 patient HCQ ICU study: 29% lower mortality (p=0.07).
Retrospective 215 mechanically ventilated COVID-19 patients in Brazil, 71 treated with HCQ, showing lower mortality with treatment in unadjusted results, without statistical significance. Authors note HCQ was used more toward the start of the pandemic, which may introduce confounding due to overall protocols improving over time, suggesting that the actual benefit may be greater.
Jun 2022, The J. Critical Care Medicine, https://www.sciendo.com/article/10.2478/jccm-2022-0015, https://c19p.org/osawa
Retrospective 600 hospitalized patients in Italy, showing lower mortality with HCQ treatment, without reaching statistical significance (p = 0.1).
Oct 2021, Scientific Reports, https://www.nature.com/articles/s41598-021-00243-4/, https://c19p.org/guglielmetti2
Prospective observational study of 199 hospitalized COVID-19 patients in Belgium showing a high prevalence of persistent symptoms including dyspnea and fatigue at 6 months after discharge. Pulmonary function tests revealed reduced diffusion capacity, and CT scans showed a high prevalence of persistent lung abnormalities at 3 months, mainly ground glass opacities. Logistic regression shows lower risk of persistent symptoms with HCQ treatment, without statistical significance.
Aug 2021, Int. J. Infectious Diseases, https://www.sciencedirect.com/science/article/pii/S1201971221005725, https://c19p.org/darcis
Retrospective database analysis of prior HCQ usage in South Korea, showing non-statistically significantly lower mortality and cases with treatment.
Feb 2021, Viruses 2021, https://www.mdpi.com/1999-4915/13/2/329, https://c19p.org/bae
Retrospective cohort study of RA and SLE patients not showing a significant difference in PCR+ cases. PCR+ does not distinguish asymptomatic cases or severity. There was only one death which was in the control group. No other information on severity is provided. 33% of the control group used HCQ within the last year. Remaining confounding by differences in the nature and severity of rheumatic disease is likely.
Dec 2020, Clinical Microbiology and Infection, https://www.sciencedirect.com/science/article/pii/S1198743X20307527, https://c19p.org/jung
Retrospective 218 hospitalized patients in Italy showing non-statistically significant 35% lower mortality with HCQ, hazard ratio aHR 0.65 [0.33–1.30].
Dec 2020, J. Infection and Public Health, https://www.sciencedirect.com/science/article/pii/S1876034120307516, https://c19p.org/guglielmetti
Retrospective 247 mechanically ventilated patients showing lower mortality with HCQ, but not statistically significant on multiple Cox regression. The paper gives the p value for multiple Cox (0.46) and simple Cox (0.02), but does not specify the adjusted risk values.
Nov 2020, Critical Care Explorations, https://journals.lww.com/ccejournal/Fulltext/2020/12000/Predictors_of_Mortality_and_Effect_of_Drug.10.aspx, https://c19p.org/lambermont
Retrospective 1255 patients in Spain showing lower mortality with HCQ. Subject to confounding by indication.
Nov 2020, Int. J. Antimicrobial Agents, https://www.sciencedirect.com/science/article/pii/S0924857920304696, https://c19p.org/rodriguezgonzalez
Retrospective PrEP analysis with 69 healthcare workers on PrEP HCQ, and 418 control. Authors report PCR and IgG results, with no baseline results for either. Authors note they "identified 69 HCWs receiving HCQ" while providing no information as to why or when they started HCQ. No conclusions can be drawn from this study because many workers may have been positive before starting HCQ. Only 14% of workers chose to use HCQ and they may have been motivated to do so because they had an infection. Authors perform several different adjustments, finding very different results. No information on death, hospitalization, symptoms, or severity is provided. Details on timing of serology and baseline serology status is not provided. Potential bias due to self-selection for risk. 25% of infections were detected before 7 days, indicating that they actually happened earlier (PCR false positive is very high initially). It is likely that many infections were before HCQ could reach therapeutic..
Nov 2020, J. Antimicrobial Chemotherapy, https://academic.oup.com/jac/advance-article/doi/10.1093/jac/dkaa477/5997449, https://c19p.org/revollo
Survey of Indian doctors not finding a significant effect of HCQ prophylaxis.
Nov 2020, J. Vaccines & Vaccination, S6:1000002, https://www.longdom.org/open-access/no-role-of-hcq-in-covid19-prophylaxis-a-survey-amongst-indian-doctors.pdf, https://c19p.org/datta
Retrospective matched case-control prophylaxis study for HCQ, ivermectin, and vitamin C with 372 healthcare workers, showing lower COVID-19 incidence for all treatments, with statistical significance reached for ivermectin. HCQ OR 0.56, p = 0.29 Ivermectin OR 0.27, p < 0.001 Vitamin C OR 0.82, p = 0.58
Nov 2020, PLOS ONE, https://journals.plos.org/plosone/article?id=10.1371/journal.pone.0247163, https://c19p.org/behera
Retrospective 164 ICU patients in Mexico showing 32% lower mortality with HCQ+AZ and 37% lower with CQ. HCQ+AZ vs. neither HCQ or CQ relative risk RR 0.68, p = 0.03 CQ vs. neither HCQ or CQ relative risk RR 0.63, p = 0.02 HCQ+AZ or CQ vs. neither relative risk RR 0.65, p = 0.006
Oct 2020, Heart & Lung, https://www.sciencedirect.com/science/article/pii/S014795632030412X, https://c19p.org/namendyssilva
607 patient HCQ late treatment study: 20% lower mortality (p=0.36).
Retrospective 607 patients reporting results for early outpatient HCQ use with mortality odds ratio OR 0.092 [0.022-0.381], p = 0.001 (65 patients), and for hospital use, mortality odds ratio OR 0.737 [0.38-1.41], p = 0.36 (558 patients). Median age 69.
Oct 2020, eClinicalMedicine, https://www.sciencedirect.com/science/article/pii/S2589537020303357, https://c19p.org/guisadovasco
Retrospective study of 367 hematology patients with COVID-19 in Spain. Among 216 patients with very severe COVID-19, there was significantly lower mortality with azithromycin treatment. Mortality was also lower with HCQ, but without statistical significance.
Aug 2020, Experimental Hematology & Oncology, https://ehoonline.biomedcentral.com/articles/10.1186/s40164-020-00177-z, https://c19p.org/pinana
Retrospective 539 COVID-19 hospitalized patients in Milan, with treatment a median of 1 day after admission, showing lower mortality with HCQ and with HCQ+AZ, with statistical significance only for HCQ+AZ.
Jul 2020, Int. J. Infectious Diseases, https://www.ijidonline.com/article/S1201-9712(20)30600-7/fulltext, https://c19p.org/darminiomonforte
Retrospective 283 COVID-19+ diabetes patients in China, showing non-statistically significant lower mortality with HCQ/CQ treatment.
May 2020, The American J. Tropical Medicine and Hygiene, https://www.ajtmh.org/configurable/content/journals$002ftpmd$002f103$002f1$002farticle-p69.xml?t:ac=journals%24002ftpmd%24002f103%24002f1%24002farticle-p69.xml, https://c19p.org/luo3h
Small 52 patient retrospective study of patients with acute respiratory failure showing lower rates of intubation with HCQ.
Nov 2020, Research Square, https://www.researchsquare.com/article/rs-113418/v1, https://c19p.org/capsoni
70 patient HCQ prophylaxis study: 50% lower mortality (p=0.67).
Retrospective hospitalized rheumatic disease patients showing 50% lower mortality for patients on HCQ.
Oct 2020, medRxiv, https://www.medrxiv.org/content/10.1101/2020.10.26.20219154v1, https://c19p.org/arleo
Retrospective 255 mechanical ventilation patients in USA, showing that weight-adjusted HCQ+AZ improved survival by over 100%. QTc prolongation did not correlate with cumulative HCQ dose or HCQ serum level. Although authors mention immortal time bias, full details on the timing of HCQ administration is not provided and this is not fully addressed. Survival curves indicate immortal time bias will significantly change results, although the observed benefit appears to exceed the potential bias.
May 2021, medRxiv, https://www.medrxiv.org/content/10.1101/2021.05.28.21258012v1, https://c19p.org/smith
Small limited trial with 100 patients concluding that HCQ improved clinical outcome, OR 0.016 [0.002-0.11] in regression analysis.
Apr 2020, medRxiv doi:10.1101/2020.04.20.20072421, https://www.researchgate.net/publication/341197843_COVID-19_in_Iran_a_comprehensive_investigation_from_exposure_to_treatment_outcomes, https://c19p.org/ashraf
Retrospective 80 ICU patients, 22 SOC, 20 lopinavir/ritonavir, 38 HCQ. 28 day mortality 24% (HCQ) versus 41% (SOC), a 41% decrease, but not statistically significant due to very small sample sizes. No statistically significant differences found for treatment escalation, ventilator-free days, viral load, or mortality. Authors consider treatment escalation more important than mortality, for unknown reasons.
Jul 2020, Critical Care, 2020, https://ccforum.biomedcentral.com/articles/10.1186/s13054-020-03117-9, https://c19p.org/lecronier
Retrospective 346 hospitalized patients in Iraq, showing lower mortality with HCQ in unadjusted results. HCQ results are only provided within the 93% of patients treated with enoxaparin.
Oct 2022, Current Issues in Pharmacy and Medical Sciences, https://www.sciendo.com/article/10.2478/cipms-2022-0020, https://c19p.org/assad
Physician survey in India with 164 ivermectin prophylaxis, 129 HCQ prophylaxis, and 81 control patients, showing significantly lower COVID-19 cases with treatment. Details of the treatment and control groups and the definition of cases are not provided, and the results are subject to survey bias. Authors also report on community prophylaxis but present only combined ivermectin/HCQ results.
Nov 2021, J. the Association of Physicians India, https://www.researchgate.net/publication/356294136_Ivermectin_and_Hydroxychloroquine_for_Chemo-Prophylaxis_of_COVID-19_A_Questionnaire_Survey_of_Perception_and_Prescribing_Practice_of_Physicians_vis-a-vis_Outcomes, https://c19p.org/samajdarh
Retrospective database study of 1,021 patients in Ecuador, Germany, Italy, and Spain, showing HCQ propensity score adjusted mortality odds ratio aOR 0.88, p=0.005.
Nov 2020, Internal and Emergency Medicine, https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7649104/, https://c19p.org/nunezgil
Very small retrospective of 12 dialysis patients showing 1/11 deaths with HCQ and 1/1 without HCQ.
Nov 2020, Nefrología, https://www.sciencedirect.com/science/article/pii/S0211699520301661, https://c19p.org/maldonado
Retrospective 12 hospitalized patients in India treated with CQ and 17 controls, showing faster recovery with treatment. There was no significant difference in viral clearance. The CQ group mean age was 41.3 vs. 47.6 for controls.
Oct 2020, Advances in Respiratory Medicine, https://journals.viamedica.pl/advances_in_respiratory_medicine/article/view/69692, https://c19p.org/niwas
Very small early-terminated underpowered PrEP RCT with 64/61 HCQ/control patients and only 8 infections, HCQ infection rate 6.3% versus control 6.6%, RR 0.95 [0.25 - 3.64]. There was no hospitalization or death, no significant difference in QTc, no severe adverse events, no cardiac events (e.g., syncope and arrhythmias) observed. Medication adherence was 81%. Therapeutic levels of HCQ may not have been reached by the time of the infection in the first week. 2 infections were reported to be after discontinuation of the medication, but the authors do not specify which arm these were in. Hypothetically, if these were both in the HCQ arm, the resulting RR for treatment would be much lower.
Sep 2020, JAMA Internal Medicine, https://jamanetwork.com/journals/jamainternalmedicine/fullarticle/2771265, https://c19p.org/abella
Retrospective 459 patients in Iran with 93% treated with HCQ, showing HCQ mortality RR 0.45, p = 0.028. HCQ was the only antiviral that showed a significant difference. There was relatively few control patients and the result is subject to confounding by indication. Average admission delay 5.72 days.
Sep 2020, The Tohoku J. Experimental Medicine, https://www.jstage.jst.go.jp/article/tjem/252/1/252_73/_article/-char/ja/, https://c19p.org/alamdari
Prospective study of 38 hospitalized rheumatic disease patients with COVID-19 in Spain, showing no mortality with existing HCQ use compared to 32% without, not reaching statistical significance. Authors also report on the use of HCQ/CQ after hospitalization. The prophylaxis and late treatment results are listed separately [Santos, Santos].
Jul 2020, Clinical Rheumatology, https://link.springer.com/10.1007/s10067-020-05301-2, https://c19p.org/santos
Late stage RCT of 667 hospitalized patients with up to 14 days of symptoms at enrollment and receiving up to 4 liters per minute supplemental oxygen, not finding a significant effect after 15 days. Authors note: "the trial cannot definitively rule out either a substantial benefit of the trial drugs or a substantial harm", sample sizes are too small. The paper uses the terms mild and moderate, however all patients had serious enough disease to be hospitalized, and 14% were actually randomized in the ICU. The trial had significant protocol deviations and unusually low medication adherence. Randomization resulted in 64.3% male patients (HCQ) vs. 54.2% (control) which may significantly affect results due to the much higher risk for male patients. Authors note: "our aim was to exclude patients already receiving longer and potentially therapeutic doses of the study treatments" in explanation for why the study protocol was changed to exclude patients with previous use of..
Jul 2020, NEJM, https://www.nejm.org/doi/full/10.1056/NEJMoa2019014, https://c19p.org/cavalcanti
Remote post-exposure prophylaxis RCT reporting that "[HCQ] did not prevent illness compatible with Covid-19 or confirmed infection when used as postexposure prophylaxis within 4 days after exposure". However, this statement is incorrect - cases were reduced, just without statistical significance - it's not possible to conclude there was no efficacy. Additionally, treatment was not within 4 days - there was up to 68 hours shipping delay as below. Further, 6 independent analyses of the data in this study indicate efficacy: [arxiv.org, blog.philbirnbaum.com, drive.google.com, longdom.org, medrxiv.org, osf.io, researchgate.net]. COVID-19 cases were reduced by [49%, 29%, 16%] respectively when taken within ~[70, 94, 118] hours of exposure (including shipping delay). The treatment delay-response relationship is significant at p=0.002. For more detailed analysis, see [c19hcq.org]. See also: [nejm.org]. Authors compare with treatment with folic acid. [Kaur] et al. note that folic..
Jun 2020, NEJM, June 3 2020, https://www.nejm.org/doi/full/10.1056/NEJMoa2016638, https://c19p.org/boulwarepep
30 patient HCQ late treatment PSM study: 25% faster recovery (p=0.45), 13% longer hospitalization (p=0.75), and no change in viral clearance (p=0.99).
Retrospective 25 hospitalized patients treated with cephalosporin, azithromycin, and HCQ, and 217 SOC patients in South Korea, reporting no significant differences. 5 patients receiving lopinavir/ritonavir and HCQ >5 days were excluded for unknown reasons. HCQ was typically initiated based on progression or side effects from another treatment. Conflicting results are reported. Table 2 indicates 15 CA/HCQ patients after matching, while Table S2 shows 25, and the Table 3 count is blank. S2 appears to incorrectly show before matching results, and the after matching results are missing in Table 3. 200mg HCQ bid.
May 2022, PLOS ONE, https://journals.plos.org/plosone/article?id=10.1371/journal.pone.0267645, https://c19p.org/hong2
Retrospective case-control study of 140 COVID-19 patients with autoimmune rheumatic diseases (AIRDs) and 140 matched controls showing higher rates of hospitalization, oxygen therapy, and mechanical ventilation with AIRDs. For the AIRD patients, there was no significant difference in outcomes based on HCQ use (only 10 patients).
Aug 2024, Medicina, https://www.mdpi.com/1648-9144/60/9/1377, https://c19p.org/rutskayamoroshan
Retrospective 15 pediatric patients in Spain, showing faster viral clearance with HCQ+AZ, without statistical significance. Treatment time and details are not provided.
Apr 2022, Anales de Pediatría, https://www.sciencedirect.com/science/article/pii/S1695403321000126, https://c19p.org/bassetsbosch
Retrospective 50 COVID-19 patients that take chronic HCQ, compared to a matched sample of patients not taking chronic HCQ, showing lower mortality and ICU admission, and shorter hospitalization for HCQ patients, but not statistically significant due to the small number of events. The actual benefit for HCQ could be much larger. The study does not address the risk of being sick enough to visit the hospital. HCQ users are likely systemic autoimmune disease patients and authors do not adjust for the very different baseline risk for these patients. Other research shows that the risk of COVID-19 for systemic autoimmune disease patients is much higher overall, Ferri et al. show OR 4.42, p<0.001 [Ferri].
Jan 2021, J. the American Academy of Dermatology, https://www.sciencedirect.com/science/article/pii/S0190962221001109, https://c19p.org/rangel
Retrospective 117 patients showing lower mortality for HCQ patients, without statistical significance. Version 1 of this paper stated: "HCQ, AZ, [and ...] were found to be independently associated with survival when treatment commenced at FACTCLINYCoD scores <3". FACTCLINYCoD scores predict mortality risk based on severity markers and comorbidities.
Sep 2020, medRxiv, https://www.medrxiv.org/content/10.1101/2020.09.05.20184655v2, https://c19p.org/synolaki
Retrospective study focused on eosinophil recovery with 9,644 hospitalized patients in Spain, showing lower mortality for HCQ (14.7% vs 29.2%, p<0.001), and AZ (15.3% vs. 18.4%, p<0.001). With a multivariate model including potential confounding factors, HCQ and AZ are associated with lower mortality, HCQ OR 0.662, p=0.057.
Aug 2020, medRxiv, https://www.medrxiv.org/content/10.1101/2020.08.18.20172874v1, https://c19p.org/gonzalez2
Retrospective 100 hospitalized patients in Spain showing lower mortality with HCQ+AZ.
Jul 2020, Research Square, https://www.researchsquare.com/article/rs-39421/v1, https://c19p.org/trullas
Retrospective 63,369 hospitalized COVID-19 survivors aged 60 years or older in Korea, showing lower 1-year mortality with macrolides (including azithromycin), higher 1-year mortality with corticosteroids (including dexamethasone and methylprednisolone), and no significant difference with HCQ (only used for 0.2% of patients).
Oct 2024, Scientific Reports, https://www.nature.com/articles/s41598-024-76871-3, https://c19p.org/kim21h
Retrospective 3,074 patients with antimalarial prescriptions and 58,955 matched controls, showing no significant differences with antimalarial prophylaxis for PCR+ cases (99% HCQ). Authors provide only PCR+ and mortality outcomes, and do not provide intermediate clinical outcomes that may show a statistically significant benefit. Authors do not adjust for the very different baseline risk for systemic autoimmune disease patients. Other research shows that the risk of COVID-19 for systemic autoimmune disease patients is much higher overall, Ferri et al. show OR 4.42, p<0.001 [Ferri] (for symptomatic disease).
Jun 2023, J. Drugs in Dermatology, https://jddonline.com/articles/dermatology/S1545961623P0840X, https://c19p.org/klebanov
Retrospective 829 hospitalized COVID-19 patients in Spain focused on gastrointestinal symptoms, showing lower risk of severe COVID-19 with HCQ treatment in bivariate analysis, without statistical significance.
Jun 2023, Gastroenterología y Hepatología, https://www.sciencedirect.com/science/article/pii/S2444382423001104, https://c19p.org/cardenasjaen
Retrospective hospitalized patients in the United Arab Emirates, showing no significant difference in viral clearance with different combinations of HCQ, AZ, favipiravir, and lopinavir/ritonavir.
Apr 2022, Antibiotics, https://www.mdpi.com/2079-6382/11/4/498, https://c19p.org/hafez
Retrospective 296 hospitalized patients in France, showing no significant difference with HCQ treatment.
Feb 2022, Infectious Diseases Now, https://www.sciencedirect.com/science/article/pii/S266699192200032X, https://c19p.org/beaumont
Retrospective 40 pediatric hospitalized patients, 15 treated with HCQ, showing 7.2 vs. 8.2 days until PCR-, not quite reaching statistical significance.
Sep 2021, Northern Clinics of Istanbul, https://northclinist.com/jvi.aspx?pdir=nci&plng=eng&un=NCI-65471&look4=, https://c19p.org/uygen
Small prophylaxis survey showing lower, but not statistically significant, progression to pneumonia (3 of 148 HCQ, 12 of 416 control), RR 0.70, p = 0.77. There was a higher incidence of cases with HCQ, OR 1.19, p = 0.58, which may be due to survey bias, treatment self-selection, and inconsistent regimens. Improvement on severity may be related to the higher HCQ concentration in lung tissue, and also reflect that binary PCR does not distinguish replication-competence. Details of the pneumonia numbers for treatment/control are from the author, it's unclear why the lower progression to pneumonia was not reported in the paper.
Dec 2020, Infectious Diseases and Clinical Microbiology, https://www.idcmjournal.org/hqn-use-among-physicians-during-the-pandemic, https://c19p.org/gonenli
Small retrospective study of 73 diabetic patients in Belgium, 55 HCQ patients, showing HCQ RR 0.87, p = 1.0.
Dec 2020, Diabetes & Metabolic Syndrome: Clinical Research & Reviews, https://www.sciencedirect.com/science/article/pii/S1871402120305154, https://c19p.org/orioli
Retrospective 4020 hospitalized patients in China showing non-statistically significant lower risk of acute kidney injury with HCQ.
Dec 2020, Nephrology Dialysis Transplantation, https://academic.oup.com/ndt/article/35/12/2095/6020340, https://c19p.org/peng
Small prospective study of 43 hospitalized patients with 39 taking HCQ, showing unadjusted mortality relative risk RR 0.41, p=0.23.
Nov 2020, Medicina Intensiva, https://www.sciencedirect.com/science/article/pii/S2173572720301739, https://c19p.org/rodriguez
Retrospective 238 hospitalized patients in Spain showing lower mortality with HCQ, adjusted hazard ratio aHR 0.81 [0.24-2.76].
Jul 2020, Medicina Clínica, https://www.sciencedirect.com/science/article/pii/S0025775320304486, https://c19p.org/riveraizquierdo
Retrospective of 89 hospitalized patients, survival HR 0.89 [0.23-3.47], not statistically significant. Authors note that unmeasured confounders may have persisted and the study may be underpowered.
Jun 2020, Clinical Infectious Diseases, https://academic.oup.com/cid/article/doi/10.1093/cid/ciaa791/5859555, https://c19p.org/paccoud
Retrospective 45 ICU patients, 17 treated with HCQ+AZ, showing no significant difference in viral clearance after 6 days, or mortality 6 days from ARDS.
May 2020, Ann. Intensive Care, https://annalsofintensivecare.springeropen.com/articles/10.1186/s13613-020-00678-4, https://c19p.org/hraiech
Retrospective 807 hospitalized patients, no statistically significant reduction in mortality or the need for mechanical ventilation with HCQ or HCQ+AZ, or for death with HCQ+AZ, HR 1.83, p=0.009 for HCQ mortality. The preprint notes that HCQ was more likely to be prescribed to patients with more severe disease, however this was deleted in the published version. 425 patients had dispositions of death or discharge by the end of the study period and thus did not encounter the issue of length-biased sampling and differential rates of right-censored observations among the groups. Also see: [mediterranee-infection.com]
Apr 2020, Med, https://www.sciencedirect.com/science/article/pii/S2666634020300064, https://c19p.org/magagnoli
Retrospective 1,072 hospitalized patients in Kazakhstan showing no mortality for HCQ treated patients, however only 23 patients received treatment - this result is not statistically significant.
Jan 2021, medRxiv, https://www.medrxiv.org/content/10.1101/2021.01.06.20249091v1, https://c19p.org/yegerov
Retrospective database study of 5683 patients, 692 received HCQ/CQ+AZ, 200 received HCQ/CQ, 203 received ivermectin, 1600 received AZ, 358 received ivermectin+AZ, and 2630 received standard of care. This study includes anyone with ICD-10 COVID-19 codes which includes asymptomatic PCR+ patients, therefore many patients in the control group are likely asymptomatic with regards to SARS-CoV-2, but in the hospital for another reason. For those that had symptomatic COVID-19, there is also likely significant confounding by indication. In this study all medications show higher mortality at day 30, which is consistent with asymptomatic (for COVID-19) or mild condition patients being more common in the control group. For ivermectin they show 30 day mortality aHR = 1.39 [0.88 - 2.22]. KM curves show that the treatment groups were in more serious condition, and also that after about day 35 survival became better with ivermectin. The last day available for ivermectin shows RR 0.83, p = 0.01. More..
Oct 2020, medRxiv, https://www.medrxiv.org/content/10.1101/2020.10.06.20208066v1, https://c19p.org/sotobecerra
Retrospective database analysis focused on famotidine but also showing results for HCQ users, with unadjusted mortality RR 0.85, p<0.001 (13.6% vs. 16.1%).
Sep 2020, medRxiv, https://www.medrxiv.org/content/10.1101/2020.09.23.20199463v1, https://c19p.org/shoaibi
Retrospective database analysis of 374,229 patients in the USA, showing no significant difference with HCQ use, however authors do not adjust for the very different baseline risk for systemic autoimmune disease patients. Other research shows that the risk of COVID-19 for systemic autoimmune disease patients is much higher overall, Ferri et al. show OR 4.42, p<0.001 [Ferri]. Authors compare with patients that never used HCQ and with patients that previously used HCQ. The comparison with patients previously using HCQ is more relevant because the matching of patients with systemic autoimmune disease is likely to be better.
Sep 2021, PLoS ONE, https://journals.plos.org/plosone/article?id=10.1371/journal.pone.0266922, https://c19p.org/fung
Retrospective 491 ICU patients in Spain showing lower mortality with HCQ without statistical significance in unadjusted results.
Jun 2023, Respiratory Research, https://respiratory-research.biomedcentral.com/articles/10.1186/s12931-023-02462-x, https://c19p.org/degonzalocalvo
Retrospective 71 hospitalized haematologic patients in Spain, showing lower mortality with HCQ treatment in unadjusted results and without statistical significance.
Jan 2022, Clinical Infection in Practice, https://www.sciencedirect.com/science/article/pii/S259017022200005X, https://c19p.org/fernandezcruz
Retrospective 277 hospitalized patients in Italy, showing lower mortality with HCQ treatment, not reaching statistical significance, and subject to confounding by indication.
Sep 2021, PharmAdvances, http://www.pharmadvances.com/a-retrospective-analysis-on-pharmacological-approaches-to-covid-19-patients-in-an-italian-hub-hospital-during-the-early-phase-of-the-pandemic-2/, https://c19p.org/menardi
Retrospective 689 healthcare workers in India, showing no significant difference in IgG positivity with HCQ prophylaxis in unadjusted results.
Feb 2021, American J. Blood Research, https://www.ncbi.nlm.nih.gov/labs/pmc/articles/PMC8010601/, https://c19p.org/mahto
Retrospective 134 hospitalized COVID-19 patients in India, showing no significant difference with HCQ treatment in unadjusted results.
Dec 2020, Indian J. Critical Care Medicine, https://www.ijccm.org/doi/pdf/10.5005/jp-journals-10071-23599, https://c19p.org/mahaleh
Retrospective multiple myeloma patients showing lower mortality with HCQ treatment, unadjusted RR 0.67, p = 0.17 (data is in the supplementary material).
Dec 2020, Blood, https://www.sciencedirect.com/science/article/pii/S0006497120839044, https://c19p.org/chari
Retrospective 630 elderly patients in Spain showing lower mortality with HCQ treatment, unadjusted relative risk RR 0.78, p = 0.09. HCQ was used more often with patients that were hospitalized (24% versus 3% use in the nursing homes). Median age 87.
Dec 2020, J. the American Medical Directors Association, https://www.sciencedirect.com/science/article/pii/S1525861020310525, https://c19p.org/bielza
Low molecular weight heparin study also showing results for HCQ treatment, unadjusted HCQ mortality relative risk RR 0.66, p = 0.61.
Nov 2020, Thrombosis Research, https://www.sciencedirect.com/science/article/pii/S0049384820306277, https://c19p.org/qin
Prospective study of 38 hospitalized rheumatic disease patients with COVID-19 in Spain, showing no mortality with existing HCQ use compared to 32% without, not reaching statistical significance. Authors also report on the use of HCQ/CQ after hospitalization. The prophylaxis and late treatment results are listed separately [Santos, Santos].
Jul 2020, Clinical Rheumatology, https://link.springer.com/10.1007/s10067-020-05301-2, https://c19p.org/santos2
Retrospective 152 mechanically ventilated patients in the USA showing unadjusted lower mortality with vitamin C, vitamin D, HCQ, and zinc treatment, statistically significant only for vitamin C.
Jul 2020, J. Clinical Anesthesia, https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7369577/, https://c19p.org/krishnan
Retrospective 167 multiple myeloma patients in Spain, showing no significant difference in mortality with HCQ treatment in unadjusted results without group details.
Jun 2020, Blood Cancer J., https://www.nature.com/articles/s41408-020-00372-5, https://c19p.org/martinezlopez
Study focused on remdesivir but with results for HCQ in the supplementary appendix, showing 9% death with HCQ versus 12% control, unadjusted relative risk uRR 0.78, p = 0.46.
May 2020, NEJM, https://www.nejm.org/doi/10.1056/NEJMoa2015301, https://c19p.org/goldmanh
Retrospective 92 ICU patients with almost all treated with HCQ and only one non-HCQ treated patient that died, showing unadjusted non-statistically significant lower mortality with treatment.
Mar 2021, medRxiv, https://www.medrxiv.org/content/10.1101/2021.03.08.21253121v1, https://c19p.org/martinvicente
Prospective observational study of 131 COVID-19 patients in Jordan, showing 18% shorter hospital stay with HCQ, p = 0.11.
Dec 2020, F1000Research, https://f1000research.com/articles/9-1439, https://c19p.org/alqassieh
Retrospective 199 sarcoidosis patients showing non-statistically significant HCQ RR 0.83, p=1.0.
Jul 2020, Research Square, https://www.researchsquare.com/article/rs-41653/v1, https://c19p.org/desbois
Retrospective 93 hospitalized patients in Saudi Arabia showing a non-statistically significant 15% reduction in PCR positive results at day 5, RR 0.85, p = 0.65. The treatment group had significantly more severe illness and significantly more male patients.
May 2020, medRxix, https://www.medrxiv.org/content/10.1101/2020.05.08.20095679v1, https://c19p.org/shabrawishi
30 moderate hospitalized cases, all recovered. Time to RNA negative comparable. Less frequent radiological progression with HCQ but not statistically significant. One HCQ patient developed to a severe case. Treatment group 4 years older and with higher incidence of hypertension.
Mar 2020, J. Zhejiang University, https://pubmed.ncbi.nlm.nih.gov/32391667/, https://c19p.org/chenmedsci
Small 108 patient RCT comparing HCQ vs. remdesivir in very late stage treatment. All patients received tocilizumab. There were significant unadjusted baseline differences in ventilation and ICU admission. NCT04779047. REC-H-PhBSU-21011.
Nov 2021, J. Infection and Public Health, https://www.sciencedirect.com/science/article/pii/S1876034121003452, https://c19p.org/sarhan
Prospective study of 245 hospitalized patients, 121 treated with HCQ, showing lower (non-statistically significant) mortality and higher ventilation at 30 days. Confounding by indication is likely.
Mar 2021, Cureus, https://www.cureus.com/articles/53247-clinical-features-and-prognostic-factors-of-245-portuguese-patients-hospitalized-with-covid-19, https://c19p.org/salvador
Retrospective 1,214 hospitalized patients in Pakistan, 77 HCQ patients, showing 33% lower mortality with HCQ, multivariate Cox HR 0.67, p = 0.34.
Dec 2020, medRxiv, https://www.medrxiv.org/content/10.1101/2020.12.13.20247254v1, https://c19p.org/naseem
80 patient HCQ late treatment study: 17% lower mortality (p=0.5).
Retrospective 80 hospitalized severe COVID-19 patients in Turkey, showing no significant difference with HCQ treatment in unadjusted results. All patients received favipiravir.
Jul 2023, Acta Clinica Croatica, https://www.researchgate.net/publication/372951875_FACTORS_AFFECTING_PROGNOSIS_AND_MORTALITY_IN_SEVERE_COVID-19_PNEUMONIA_PATIENTS, https://c19p.org/afsin
Retrospective 679 healthcare workers post COVID-19 discharge, 76 using HCQ prophylaxis, showing no significant difference in PASC.
Dec 2022, The Lancet Regional Health - Southeast Asia, https://www.sciencedirect.com/science/article/pii/S2772368222001469, https://c19p.org/shukla
Retrospective 505 ECMO patients showing no significant difference in mortality in unadjusted results.
Feb 2022, The Annals of Thoracic Surgery, https://www.sciencedirect.com/science/article/abs/pii/S0003497522001989, https://c19p.org/hall
Retrospective 93 hospitalized patients in Saudi Arabia, 45 treated with CQ/HCQ, showing no significant difference in viral clearance. More patients treated with CQ/HCQ had severe cases at baseline (20% vs. 2%).
Jan 2022, Cureus, https://www.cureus.com/articles/82181-negative-nasopharyngeal-sars-cov-2-pcr-conversion-in-response-to-different-therapeutic-interventions, https://c19p.org/alwafi
Retrospective 180 hospitalized COVID-19 patients in Sierra Leone, showing no significant difference with HCQ treatment in unadjusted results, however HCQ was significantly more likely to be used for severe patients (33% vs. 12%).
Jan 2022, Infectious Diseases & Immunity, https://journals.lww.com/10.1097/ID9.0000000000000037, https://c19p.org/tu
Retrospective 205 patients in Italy, 160 treated with HCQ, showing lower mortality with treatment in multivariate analysis, but not reaching statistical significance.
Jun 2021, Vaccines, https://www.mdpi.com/2076-393X/9/6/640, https://c19p.org/turrini
Retrospective 991 hospitalized patients in Iran focusing on aspirin use but also showing results for HCQ, remdesivir, and favipiravir.
Apr 2021, J. Medical Virology, https://onlinelibrary.wiley.com/doi/10.1002/jmv.27053, https://c19p.org/hajiaghajani
Tiny retrospective database analysis of hospitalized COVID-19 patients with rheumatologic disease containing 14 chronic HCQ and 28 control patients. Patients are very poorly matched. Bias against HCQ is clear in the abstract which mentions differences favoring HCQ but ignores those favoring control (large differences in ethnicity, rheumatic conditions, hypertension, coronary artery disease, solid organ transplant recipients, immunosuppresive drugs). 61% of control patients also received HCQ. Adherence for chronic HCQ patients was not examined. Despite the very large differences between the groups, no adjustments are made. The study claims that HCQ did not prevent severe cases, but the study is among hospitalized patients, i.e., they already have cases severe enough for hospitalization - this study can not identify a protective effect of HCQ that reduces the probability of disease severe enough for hospitalization.
Mar 2021, Rheumatology Advances in Practice, https://academic.oup.com/rheumap/advance-article/doi/10.1093/rap/rkab014/6156645, https://c19p.org/pham
Retrospective ICU patients in the Philippines showing unadjusted HCQ RR 0.82, p = 0.64.
Jan 2021, Critical Care Research and Practice, https://www.hindawi.com/journals/ccrp/2021/7510306/, https://c19p.org/ubaldo
79 patient HCQ late treatment study: 16% lower mortality (p=0.76).
Retrospective 79 hospitalized nonagenarian patients showing unadjusted HCQ mortality RR 0.84, p = 0.76.
Jan 2021, Revista Espanola de Quimioterapia, https://europepmc.org/article/med/33522213, https://c19p.org/roig
Survey analysis of 1,858 RA patients in Iran, showing no significant difference in cases with HCQ prophylaxis.
Jan 2021, Postgraduate Medical J., https://pmj.bmj.com/content/early/2021/01/13/postgradmedj-2020-139561, https://c19p.org/khoubnasabjafari
Retrospective 255 hospitalized patients, 65 treated with HCQ, showing unadjusted RR 0.87, p=0.63. Confounding by indication is likely.
Oct 2020, Int. J. Infectious Diseases, https://www.sciencedirect.com/science/article/pii/S1201971220322761, https://c19p.org/tehrani
Retrospective 51 ICU patients under mechanical ventilation, 33 treated with HCQ, showing unadjusted lower mortality with treatment.
Aug 2020, J. Antimicrobial Chemotherapy, https://academic.oup.com/jac/article/75/11/3359/5896161, https://c19p.org/pasquini
Retrospective study of late stage use on 2,512 hospitalized patients showing no significant differences in associated mortality for patients receiving any HCQ during the hospitalization (HR, 0.99 [95% CI, 0.80-1.22]), HCQ alone (HR, 1.02 [95% CI, 0.83-1.27]), or HCQ+AZ (HR, 0.98 [95% CI, 0.75-1.28]). Misclassification is possible due to manual abstraction of EHR data. They observed a change in the prescribing patterns of HCQ during the study timeframe. Confounding by indication.
May 2020, PLoS ONE, https://journals.plos.org/plosone/article?id=10.1371/journal.pone.0237693, https://c19p.org/ip2
Study of 349 low-risk hospitalized patients with 151 non-consenting or ineligible patients used as controls. SOC included zinc, vitamin C and vitamin D. A statistically significant improvement in PCR negativity is shown at day 7 with HCQ treatment, 52.1% (HCQ) versus 35.7% (control), p=0.001, but no statistically significant difference at day 14, or in progression. Patients were relatively young and there was no mortality. Only 3% of patients had any disease progression and all patients recovered, so there is little if any room for treatment benefit. Progression among higher-risk patients with comorbidities was lower with treatment (12.9% versus 28.6%, p=0.3, very few cases). Despite the title, this is not an RCT since patients self-selected the arm, or were chosen based on allergies/contraindications. The treatment group had about twice the number of patients with comorbidities. Treatment delay is unknown - it was recorded but not reported in the paper. Viral load was not measured...
Aug 2020, medRxiv, https://www.medrxiv.org/content/10.1101/2020.07.30.20165365v1, https://c19p.org/kamran
Retrospective 831 hospitalized COVID-19 patients showing lower mortality with HCQ in unadjusted results, without statistical significance.
Aug 2024, Cureus, https://www.cureus.com/articles/263779-anticoagulant-use-in-covid-19-patients-a-longitudinal-study-from-zanjan-iran, https://c19p.org/azimipirsaraeih
Retrospective 668 hospitalized patients in Argentina, 18 treated with HCQ, not showing a significant difference in unadjusted results.
Jul 2021, medRxiv, https://www.medrxiv.org/content/10.1101/2021.07.30.21261220v1, https://c19p.org/barra
Retrospective of hospitalized patients with 31 HCQ patients and 195 standard treatment patients, not showing a significant difference in terms of viral clearance or recovery. There was no mortality in either group. "It is notable that HQ plus antibiotics group had worse baseline clinical profiles (i.e. higher percentage of moderate severity patients, more patients with fever >=37.5C, higher average body temperature) and prognostic indicators such as age, LDH, lymphocyte count, and CRP". We note that propensity score matching removed almost all of the male patients in the control group (40% -> 5%) but increased the percentage of male patients in the treatment group. This provides a large advantage to the control group because there is a very large difference in severity and mortality based on gender [ncbi.nlm.nih.gov]. In terms of viral RNA clearance we note that other research has found that "active viral replication drops quickly after the first week, and viable virus..
Jul 2020, medRxiv, https://www.medrxiv.org/content/10.1101/2020.07.04.20146548v1, https://c19p.org/an
EHR analysis of 3,372 hospitalized COVID-19 patients not showing a significant difference for mortality or the risk of mechanical ventilation. Subject to the limitations of EHR analysis. Misclassification is possible. Confounding by indication is likely.
May 2020, medRxiv, https://www.medrxiv.org/content/10.1101/2020.05.12.20099028v1, https://c19p.org/singh
Very small retrospective study of rheumatic disease patients, sample size is too small for statistical significance (HCQ 0.5-4.0%, no-HCQ 0.4-2.7%). Confirmed cases were 1 HCQ and 2 no-HCQ, confirmed+likely cases were 1 HCQ and 3 no-HCQ. 1 HCQ and 2 no-HCQ patients were admitted to hospital. We do not think a conclusion can be drawn based on these sample sizes. There are very significant differences between the groups, for example 30% of the HCQ group have SLE vs. 2.5% of the no-HCQ group. SLE patients have a 5.7 times relative risk of pneumonia according to [ncbi.nlm.nih.gov], whereas the relative risk with glucocorticoids and TNF-α inhibitors is significantly lower [academic.oup.com]. Two more recent studies with rheumatic disease/autoimmune condition patients provide higher confidence.
May 2020, medRxiv, https://www.medrxiv.org/content/10.1101/2020.05.16.20104141v1, https://c19p.org/macias
Retrospective of 4,642 hospitalized patients in France showing significantly faster discharge with HCQ and HCQ+AZ. No significant effect is seen on 28-day mortality, however many more control patients are still in hospital at 28 days. Other studies show faster resolution for HCQ, suggesting there will be a significant improvement when extending past 28 days. Hopefully authors will extend the analysis. Note that the median age is higher in the group not treated with HCQ or AZ. For other issues with the adjustments see [medrxiv.org]. Also see the analysis here [web.archive.org].
Jun 2020, medRxiv, https://www.medrxiv.org/content/10.1101/2020.06.16.20132597v1, https://c19p.org/sbidian
Retrospective 32 ICU patients, showing no significant difference with HCQ treatment in unadjusted results.
Aug 2021, Microbial Drug Resistance, https://www.liebertpub.com/doi/full-xml/10.1089/mdr.2020.0489, https://c19p.org/karrulih
Small PEP trial with 51 HCQ patients, not showing a significant difference in cases. IRCT20130917014693N10.
Aug 2021, Pulmonary Pharmacology & Therapeutics, https://www.sciencedirect.com/science/article/abs/pii/S109455392100081X, https://c19p.org/shabani
Prospective study of 966 ICU patients in France, 289 treated with HCQ, showing no significant difference with treatment. Time based confounding is likely because HCQ became increasingly controversial and less used over the time covered, while overall treatment protocols during this period improved dramatically, i.e., more control patients likely come later in the period when treatment protocols were greatly improved.
Jul 2021, Anaesthesia Critical Care & Pain Medicine, https://www.sciencedirect.com/science/article/pii/S2352556821001351, https://c19p.org/roger
Prospective study of 200 ECMO patients showing no significant difference in unadjusted results for HCQ treatment. Time based confounding is likely because HCQ became increasingly controversial and less used over the time covered (as shown in figure 4), while overall treatment protocols during this period improved dramatically, i.e., more control patients likely come later in the period when treatment protocols were greatly improved.
Jul 2021, The Annals of Thoracic Surgery, https://www.sciencedirect.com/science/article/pii/S0003497521011772, https://c19p.org/jacobs
Retrospective 147 ICU patients in Turkey, showing no significant difference in outcomes based on HCQ treatment before ICU admission. This is not very informative, for example we do not know if HCQ treated patients were much less likely to be admitted to the ICU.
Apr 2021, South. Clin. Ist. Euras., https://jag.journalagent.com/scie/pdfs/SCIE-89847-RESEARCH_ARTICLE-CIYILTEPE.pdf, https://c19p.org/ciyiltep
Retrospective database analysis case control study of rheumatic patients. When compared with other cDMARDs, HCQ users had significantly lower hospitalization, however there was no significant difference in mortality. Results differ significantly from previous studies, for example showing mortality OR 0.94 [0.83-1.06] for patients with rheumatic disease and mortality OR 0.88 [0.74-1.05] for patients with RA/SLE. Other research shows that the risk of COVID-19 for systemic autoimmune disease patients is much higher overall.
Apr 2021, Rheumatology, https://academic.oup.com/rheumatology/advance-article/doi/10.1093/rheumatology/keab348/6226505?searchresult=1, https://c19p.org/alegiani
Retrospective 840 hospitalized patients in Switzerland showing non-statistically significant lower mortality with HCQ but significantly longer hospitalization times. Confounding by indication is likely. PSM fails to adjust for severity with a 16% higher mNEWS score for HCQ vs. SOC in the matched cohort. Time varying confounding is likely. HCQ became controversial and was suspended towards the end of the period studied, therefore HCQ use was likely more frequent toward the beginning of the study period, a time when overall treatment protocols were significantly worse. Authors note: "overall, there was an indication bias, with the reason of prescription being associated with the outcome of interest. Indeed, patients with more severe COVID-19 were more likely to receive experimental therapies."
Dec 2020, Swiss Medical Weekly, https://smw.ch/article/doi/smw.2020.20446, https://c19p.org/vernaz
Retrospective database analysis with PSM not including COVID-19 severity, finding mortality OR 0.95 [0.62-1.46] for HCQ, and 1.24 [0.70-2.22] for HCQ+AZ. Confounding by indication likely.
Oct 2020, Pharmacotherapy, https://accpjournals.onlinelibrary.wiley.com/doi/10.1002/phar.2467, https://c19p.org/annie
Retrospective 1376 hospitalized patients in Italy, 211 treated with HCQ and 166 with HCQ+AZ.
Aug 2020, J, Clinical Medicine, https://www.mdpi.com/2077-0383/9/9/2800, https://c19p.org/albani
Comparison of CQ/HCQ users with the general population in a region of Italy, showing no significant difference in the probability of COVID-19. CQ/HCQ users were mostly systemic autoimmune disease patients and authors do not adjust for the very different baseline risk for these patients. Other research shows that the risk of COVID-19 for systemic autoimmune disease patients is much higher overall, Ferri et al. show OR 4.42, p<0.001 [Ferri].
Aug 2020, Arthritis & Rheumatology, https://onlinelibrary.wiley.com/doi/10.1002/art.41475, https://c19p.org/salvarani
Small study of SLE patients taking HCQ with a phone survey for COVID-19 suggestive symptoms. There was 2 hospitalizations (group not identified) and no ICU or death cases. A similar percentage of suspected infections were reported for HCQ users and non-HCQ users, RR 0.96, p = 0.93. There was no mortality and severity was not analyzed to determine if HCQ treated patients fared better. No adjustment for concomitant medications or severity of SLE. Only 5 cases were PCR confirmed.
Jun 2020, Annals of the Rheumatic Diseases, https://ard.bmj.com/content/early/2020/06/25/annrheumdis-2020-218244, https://c19p.org/gendebien
Analysis of rheumatic disease patients showing no significant association between antimalarial therapy and hospitalisation, OR=0.94 [0.57-1.57], p=0.82 after adjustments.
May 2020, Annals of the Rheumatic Diseases, 859-866, https://europepmc.org/article/med/32471903, https://c19p.org/gianfrancesco
Analysis of 80 SLE patients diagnosed with COVID-19, showing the frequency of hospitalisation did not differ between individuals using an antimalarial versus non-users (55% (16/29) vs 57% (29/51), p=ns. Authors suggest that the dosage used may be too low to reach therapeutic levels.
May 2020, Annals of the Rheumatic Diseases, https://ard.bmj.com/content/early/2020/05/20/annrheumdis-2020-217690, https://c19p.org/konig
Very small study of rheumatic disease/autoimmune disorder patients showing no significant difference but with only 3 chronic HCQ patient cases. Only considers people tested at a time when primarily symptomatic cases were tested. Other research shows that the risk of COVID-19 for systemic autoimmune disease patients is much higher overall, Ferri et al. show OR 4.42, p<0.001 [Ferri], which is the observed real-world risk, taking into account factors such as these patients potentially being more careful to avoid exposure. Adjusting for the difference in baseline risk using the result in Ferri et al. shows substantial benefit for HCQ, RR 0.211, but with only 3 HCQ cases the result is inconclusive. More recent studies with rheumatic disease/autoimmune condition patients provide higher confidence.
May 2020, Autoimmunity Reviews, July 2020, https://www.sciencedirect.com/science/article/pii/S1568997220301282, https://c19p.org/gendelman
Prospective PrEP study with low risk healthcare workers in India showing RR=0.89 [0.53-1.52]. There were no significant adverse effects. Only mean age and gender distribution are provided for baseline characteristics, no severity information is provided, and no adjustments were made. Authors analyze HCQ use for <8 vs. ≥8 weeks, noting a lack of statistical significance, but not providing the results.
Dec 2021, Expert Review of Anti-infective Therapy, https://www.tandfonline.com/doi/abs/10.1080/14787210.2022.2015326, https://c19p.org/rao
Retrospective 280 hospitalized patients in the Philippines, 25 treated with HCQ, not showing any significant differences in unadjusted results.
Nov 2021, Western Pacific Surveillance and Response J., https://ojs.wpro.who.int/ojs/index.php/wpsar/article/view/852, https://c19p.org/cortez
Retrospective 4666 people with autoimmune or inflammatory conditions, showing HCQ adjusted risk of COVID-19 OR 0.91 [0.68-1.23]. Results are not adjusted for the significantly different risk of COVID-19 depending on the type and severity of autoimmune or inflammatory condition.
Feb 2021, medRxiv, https://www.medrxiv.org/content/10.1101/2021.02.03.21251069v1, https://c19p.org/fitzgerald
Database analysis of 7,592 patients in NYC, showing adjusted HCQ mortality odds ratio OR 0.96, p = 0.82, and HCQ+AZ OR 0.94, p = 0.63
Jun 2020, medRxiv, https://www.medrxiv.org/content/10.1101/2020.06.11.20128926v1, https://c19p.org/wangrx
Retrospective 193 hospitalized patients in Brazil not finding a significant difference with HCQ. The control group was composed of patients refusing HCQ or with contraindications. Time based confounding is very likely because HCQ became more controversial in Brazil over the time covered (Mar - Jun 2020), while overall treatment protocols during this period improved dramatically, i.e., more control patients (those refusing HCQ) likely come later in the period when treatment protocols were greatly improved. The paper does not mention the word "confounding" or make any adjustments.
Feb 2021, The Brazilian J. Infectious Diseases, https://www.sciencedirect.com/science/article/pii/S141386702100012X, https://c19p.org/lamback
Retrospective database analysis of 56 mild COVID-19 patients, all treated with vitamin C, vitamin D, and zinc, comparing ivermectin + doxycycline (n=14), AZ (n=13), HCQ (n=14), and SOC (n=15), finding that all groups recover quickly, and there was no significant difference between the groups.
Mar 2021, medRxiv, https://www.medrxiv.org/content/10.1101/2021.03.08.21252883v1, https://c19p.org/royh
25 patient HCQ late treatment study: 38% improved viral clearance (p=0.17).
Early results from a very small trial, reported within the application for a later trial. Very minimal details are provided, but we include this as the earliest published results. For COVID-19 patients with pneumonia the viral negative conversion rate was 50% (5/10) with CQ versus 20% (3/15) with lopinavir/ritonavir.
Feb 2020, ChiCTR2000029741, http://www.chictr.org.cn/showproj.aspx?proj=49263, https://c19p.org/xia
Retrospective 17 rheumatoid arthritis COVID-19+ patients, 7 on HCQ treatment, showing no significant differences. They study reports only including hospitalized patients, but the results include non-hospitalized patients. Results do not reflect potential difference in the probability that a case is serious enough to have been tested and identified. Few group details are provided (even the age of patients in each group is not specified).
Jul 2021, Research Square, https://www.researchsquare.com/article/rs-43812/v1, https://c19p.org/kucukakkas
Retrospective 125 mechanically ventilated ICU patients in Iran, showing no significant difference with HCQ treatment in unadjusted results.
Mar 2022, Research Square, https://www.researchsquare.com/article/rs-1362678/v1, https://c19p.org/salehih
Retrospective hospitalized patients in Saudi Arabia showing higher mortality with most treatments although not reaching statistical significance. Confounding by indication, time, or other factors is likely (a 19x higher risk with lopinavir/ritonavir and 3.5x higher risk with azithromycin is not supported by other studies for example). The number of patients treated with HCQ is not provided.
Jul 2021, medRxiv, https://www.medrxiv.org/content/10.1101/2021.07.13.21260428v1, https://c19p.org/alhamlan
Retrospective 186 hospitalized patients in Pakistan showing unadjusted HCQ mortality RR 1.45, p = 0.07. Confounding by indication is likely.
Jan 2021, medRxiv, https://www.medrxiv.org/content/10.1101/2020.12.28.20248920v1, https://c19p.org/sarfaraz
Retrospective analysis of acute care patients in Bahrain not showing a significant effect of HCQ. Confounding by indication is likely. Matching appears not to have matched for baseline severity. 17.5% of HCQ patients required oxygen while only 12.6% of control patients did.
Nov 2020, medRxiv, https://www.medrxiv.org/content/10.1101/2020.11.25.20234914v1, https://c19p.org/abdulrahman
299 patient HCQ late treatment RCT: 15% higher mortality (p=0.7) and 24% improved viral clearance (p=0.68).
Early terminated very late stage (95% on oxygen at baseline) DISCOVERY trial. 4% more patients were on ventilation at baseline in the HCQ group. This preprint presents more recent results than the earlier journal article.
Oct 2020, medRxiv, https://www.medrxiv.org/content/10.1101/2022.02.16.22271064, https://c19p.org/discovery
Retrospective 183 hospitalized pediatric COVID-19 patients in Iran, showing no significant difference in mortality with in unadjusted results.
Jul 2023, Canadian J. Infectious Diseases and Medical Microbiology, https://www.hindawi.com/journals/cjidmm/2023/5205188/, https://c19p.org/shamsih
Retrospective HCQ users in Denmark, not showing a significant difference, however authors do not adjust for the very different baseline risk for systemic autoimmune disease patients. Authors appear unaware of research in the area, for example saying that "currently, no obvious connection exists between a known rheumatological disorder and the risk of contracting SARS-CoV-2". Many papers show that the risk of COVID-19 for systemic autoimmune disease patients is much higher overall, e.g., Ferri et al. show OR 4.42, p<0.001 [Ferri]. Supplementary data is not currently available.
May 2021, Int. J. Infectious Diseases, https://www.sciencedirect.com/science/article/pii/S1201971221004781, https://c19p.org/kamstrup
Retrospective database analysis of 7,816 Veterans Affairs hospitalized patients analyzing progression to ARDS and 30-day mortality from ARDS. Confounding by indication is likely. Chronological bias is likely, with HCQ more likely to be used earlier on, before significant improvements in overall treatment. No results are provided for HCQ for progression to ARDS.
Oct 2020, medRxiv, https://www.medrxiv.org/content/10.1101/2020.10.16.20214130v1, https://c19p.org/solh
Retrospective 65 HCQ+AZ, 20 control patients, showing median time to negative PCR of 23 days for HCQ+AZ vs. 19 days for control. Confounding by indication. 100% of non-HCQ group had mild disease vs. 63% of the HCQ+AZ group. More comorbidities and symptoms in the HCQ+AZ group.
Aug 2020, medRxiv, https://www.medrxiv.org/content/10.1101/2020.08.05.20151027v1, https://c19p.org/saleemi
Retrospective 200 hospitalized COVID-19 patients in Saudi Arabia, showing no significant difference in outcomes between HCQ and favipiravir.
Nov 2022, Pharmaceuticals, https://www.mdpi.com/1424-8247/15/12/1456, https://c19p.org/alosaimi
Retrospective very late stage hospitalized patients in New York during the first wave, showing no significant relationship between HCQ levels and outcomes. Authors note that the patients with data were the sickest patients.
Aug 2022, British J. Clinical Pharmacology, https://onlinelibrary.wiley.com/doi/10.1111/bcp.15489, https://c19p.org/lyashchenko
Retrospective 1,215 hospitalized patients in the Phillipines, showing no significant difference in outcomes with remdesivir or HCQ use in unadjusted results subject to confounding by indication.
Jul 2022, IJID Regions, https://www.sciencedirect.com/science/article/pii/S2772707622000935, https://c19p.org/malundo
Retrospective 1,418 very late stage (46% mortality) patients in Peru, showing no significant difference with HCQ. There is strong confounding by indication, for example 48% of patients with baseline SpO2 <70% were treated compared with 22% for SpO2 >95%. There may also be significant confounding by time with SOC changing substantially over the first few months of the pandemic.
Mar 2022, PLOS ONE, https://journals.plos.org/plosone/article?id=10.1371/journal.pone.0264789, https://c19p.org/sotoh
Retrospective 811 hospitalized COVID+ patients in Saudi Arabia, showing higher mortality with HCQ treatment in unadjusted results subject to confounding by indication.
Feb 2022, J. Infection and Public Health, https://www.sciencedirect.com/science/article/pii/S187603412200034X, https://c19p.org/albanghali
Retrospective 171 ICU patients in Saudi Arabia showing no significant difference for HCQ treatment in unadjusted results.
Aug 2021, Saudi Pharmaceutical J., https://www.sciencedirect.com/science/article/pii/S1319016421001559, https://c19p.org/alghamdi2
Retrospective 283 patients in the USA showing higher mortality with all treatments (not statistically significant). Confounding by indication is likely. In the supplementary appendix, authors note that the treatments were usually given for patients that required oxygen therapy. Oxygen therapy and ICU admission (possibly, the paper includes ICU admission for model 2 in some places but not others) were the only variables indicating severity used in adjustments. Time based confounding is likely because HCQ became increasingly controversial and less used over the time covered (March 1 to May 31, 2020), while overall treatment protocols during this period improved dramatically, i.e., more control patients likely come later in the period when treatment protocols were greatly improved.
Apr 2021, BMJ Open, https://bmjopen.bmj.com/content/11/4/e042549.info, https://c19p.org/gadhiya
Retrospective database analysis of 3,219 hospitalized patients in the USA. Very different results in the time period analysis (Table S2), and results significantly different to other studies for the same medications (e.g., heparin OR 3.06 [2.44-3.83]) suggest significant confounding by indication and confounding by time.
Apr 2021, BMJ Open, https://bmjopen.bmj.com/content/11/4/e042042.info, https://c19p.org/mulhem
Retrospective 775 hospitalized patients in Saudi Arabia showing no significant difference. There was no adjustment for severity or comorbidities. Confounding by indication is likely.
Mar 2021, Antibiotics, https://www.mdpi.com/2079-6382/10/4/365, https://c19p.org/alghamdi
Retrospective database analysis of 64,781 hospitalized patients in the USA, showing lower mortality with vitamin C or vitamin D (authors do not distinguish between the two), and higher mortality with zinc and HCQ, statistically significant for zinc. Authors excluded hospital-based outpatient visits, without explanation. Confounding by indication is likely, adjustments do not appear to include any information on COVID-19 severity at baseline.
Dec 2020, JAMA Network Open, https://jamanetwork.com/journals/jamanetworkopen/article-abstract/2773971, https://c19p.org/rosenthal
Retrospective 175 hospitalized COVID-19 patients in the USA, showing no significant difference in mortality with HCQ. Authors note that "patients treated with HCQ in our cohort were more likely to be sicker at baseline".
Nov 2020, HCA Healthcare J. Medicine, https://scholarlycommons.hcahealthcare.com/hcahealthcarejournal/vol1/iss0/20, https://c19p.org/aboulenain
Retrospective 313 patients, mostly critical stage and mostly requiring respiratory support, showing unadjusted RR 1.06, p = 0.77. Confounding by indication likely.
Nov 2020, Mayo Clinic Proceedings: Innovations, Quality & Outcomes, https://www.sciencedirect.com/science/article/pii/S2542454820302071, https://c19p.org/rodrigueznava
903 patient HCQ late treatment study: 37% higher mortality (p=0.28).
Convalescent plasma study also showing mortality based on HCQ treatment, unadjusted hazard ratio uHR 1.37, p = 0.28. Confounding by indication is likely.
Nov 2020, The American J. Pathology, https://www.sciencedirect.com/science/article/pii/S0002944020304892, https://c19p.org/salazar
1,402 patient HCQ late treatment study: 22% slower viral clearance (p=0.0001).
Health insurance database analysis failing to adjust for disease severity and not finding a significant difference in time to PCR- for LPV/r and HCQ. There are large differences in severity across groups. Authors did PSM but chose not to prioritize severity, resulting in incomparable groups, e.g., baseline pneumonia of 44% in the HCQ group and 15% in the control group (after PSM). Authors note this but offer no explanation for not correcting for severity: "However, the disease severity and proportion of accompanying pneumonia were still significantly higher in the LPV/r and HCQ-group".
Oct 2020, Int. J. Infectious Diseases, https://www.sciencedirect.com/science/article/pii/S1201971220322669, https://c19p.org/choi
194,637 patient HCQ prophylaxis study: 3% higher mortality (p=0.83).
Observational database study of RA/SLE patients in the UK, 194,637 RA/SLE patients with 30,569 having >= 2 HCQ prescriptions in the prior 6 months, HCQ HR 1.03 [0.80-1.33] (HR 0.78 before adjustments). 70 patients with HCQ prescriptions died. One major problem is that there is no knowlege of medication adherence for these 70 - for example, it is possible that they were part of the expected percentage of patients that did not take the medication as prescribed, invalidating the result. Other limitations include confounding by use of bDMARDs and confounding by severity of rheumatological disease.
Sep 2020, The Lancet Rheumatology, https://www.sciencedirect.com/science/article/pii/S2665991320303787, https://c19p.org/rentsch
Database analysis of 11,721 hospitalized patients, 4,232 on HCQ. Strong evidence for confounding by indication and compassionate use of HCQ. 24.9% of HCQ patients were on mechanical ventilation versus 12.2% control. Ventilation mortality was 70.5% versus 11.6%. This study does not adjust for the differences in comorbid conditions and disease severity, and therefore does not make a conclusion. Unadjusted HCQ mortality was 24.8% versus control 19.6%. Adjusting for ventilation only gives us 17.7% HCQ versus 19.6% control (adjusting the HCQ group to have the same proportion of ventilation patients), RR 0.90. Hopefully authors can do a full adjustment analysis. Comorbidities may favor control, while patients remaining in the hospital (5.3%) may favor HCQ (other studies show faster resolution for HCQ patients). Data inconsistencies have been found in this study, for example 99.4% of patients treated with HCQ were treated in urban hospitals, compared to 65% of untreated patients ..
Aug 2020, Clinical Infectious Disease, https://academic.oup.com/cid/advance-article/doi/10.1093/cid/ciaa1268/5898276, https://c19p.org/fried
Retrospective study of HCQ use in 9 hospitals in the Netherlands, showing no significant difference in mortality with HCQ/CQ. Late stage (admitted to hospital with positive test or CT scan abnormalities). 4 of 7 hospitals started treatment only after further deterioration. Short cutoff (21 days) - other studies have shown treated patient cases resolved faster and more control patients remaining in hospital at this time. In the preprint, 58 of 341 control patients died. In the journal version, 53 of 353 control patients died. Significant differences between hospitals - HCQ hospitals had significantly older patients with significantly more comorbidities. Non-HCQ hospitals were "tertiary academic centres" whereas HCQ hospitals were "secondary care hospitals". Residual confounding likely. This study compares overcrowded regular hospitals with undercrowded academic hospitals. A subset of patients were excluded due to transfer to other hospitals. This introduces bias..
Aug 2020, Clinical Microbiology and Infection, https://www.clinicalmicrobiologyandinfection.com/article/S1198-743X(20)30615-7/fulltext, https://c19p.org/peters
Retrospective 176 hospitalized patients (144 HCQ, 32 control) showing no significant differences with HCQ or TCZ. Confounding by indication.
Aug 2020, J. Medical Internet Research, https://www.jmir.org/2020/9/e21758/, https://c19p.org/roomi
Comparison of the percentage of SLE/RA patients on immunosuppressants that were taking HCQ, for COVID-19 diagnosis versus other infections or outpatient visits, finding a similar percentage in each case. No mortality of severity information is provided to determine if HCQ treated patients fared better. No adjustment for concomitant medications or severity.
Aug 2020, Annals of the Rheumatic Diseases, https://ard.bmj.com/content/early/2020/08/19/annrheumdis-2020-218500, https://c19p.org/singer
Analysis of 2,215 intensive care unit patients showing no significant differences with this very late stage use of HCQ.
Jul 2020, JAMA Intern. Med., https://jamanetwork.com/journals/jamainternalmedicine/fullarticle/2768602, https://c19p.org/gupta
Small retrospective study of 56 ICU patients in Mexico showing HCQ RR 1.1, p = 1.0.
Jun 2020, Cir Cir. 2020, 569-575, https://cirugiaycirujanos.com/frame_esp.php?id=358, https://c19p.org/sosagarcia
Analysis of hospitalized lung cancer patients with 35 of 48 taking HCQ, mortality OR 1.03, p = 0.99.
Jun 2020, Annals of Oncology, 1386-1396, https://www.annalsofoncology.org/article/S0923-7534(20)39894-X/fulltext, https://c19p.org/luo
Survey of 165 SLE patients, 127 on HCQ. 8 patients with suspected COVID-19 and 4 confirmed cases. No mortality, one ICU case. 7 patients had no symptoms despite contact with a COVID-19 patient. No adjustment for concomitant medications or severity of SLE. Confounding by indication.
May 2020, Annals of the Rheumatic Diseases, https://ard.bmj.com/content/early/2020/05/23/annrheumdis-2020-217717.info, https://c19p.org/cassione
Before propensity matching, 38 control patients had hypertension. After propensity matching, 146 patients had hypertension (Table 1). Even if all propensity matched control patients had hypertension, the control prevalence would only be 14% compared to 49% for treatment. Since patients with hypertension are at much greater risk of mortality (HR 2.12, see [academic.oup.com]), this appears to invalidate the results. Observational study of 1,446 hospitalized patients showing no significant effect on a combined intubation/death outcome for late treatment. However, secondary analysis shows the success of HCQ was hidden by combining intubation and death - death / (combined death/intubation) for HCQ was 60% vs. control 89%, for details see: [twitter.com]. RCT recommended. No AZ or Zinc. HCQ group much sicker - patients already in mild/moderate ARDS, most of the control group not in ARDS. Control cases received other therapeutics.
May 2020, NEJM, May 7, 2020, https://www.nejm.org/doi/full/10.1056/NEJMoa2012410, https://c19p.org/geleris
Analysis of autoimmune disease patients on HCQ, compared to a control group from the general population (matched on age and sex, but not adjusted for autoimmune disease), showing non-significant differences between groups. Other research shows that the risk of COVID-19 for systemic autoimmune disease patients is much higher overall, Ferri et al. show OR 4.42, p<0.001 [Ferri], which is the observed real-world risk, taking into account factors such as these patients potentially being more careful to avoid exposure. If we adjust for the different baseline risk, the mortality result becomes RR 0.35, p=0.23, suggesting a substantial benefit for HCQ treatment (as shown in other studies).
Sep 2020, medRxiv, https://www.medrxiv.org/content/10.1101/2020.08.31.20185314v1, https://c19p.org/delaiglesia
PSM retrospective 260 late stage hospitalized COVID-19 pneumonia patients in Turkey, showing no significant difference between favipiravir and HCQ.
Mar 2022, Acta Medica, https://actamedica.org/index.php/actamedica/article/view/719, https://c19p.org/uyaroglu
Retrospective 9 COVID-19 patients with antiphospholipid syndrome in Turkey, showing no significant differences based on existing HCQ treatment.
Jan 2022, Bratislava Medical J., http://www.elis.sk/index.php?page=shop.product_details&flypage=flypage.tpl&product_id=7533&category_id=179&option=com_virtuemart&vmcchk=1&Itemid=1, https://c19p.org/erden
Observational study of 927 low-risk healthcare workers in India, 731 volunteering for weekly HCQ prophylaxis, showing higher cases with treatment in unadjusted results. Clinical outcome was in the protocol, however no information on which patients were symptomatic is provided. There were no adverse events and no hospitalizations or deaths. Adherence was very low, decreasing weekly, with almost all participants discontinuing by week 11. The majority of infections occurred in later weeks when adherence was very low, and there was no per protocol analysis. #ECR/206/Inst/GJ/2013/RR-20.
Aug 2021, medRxiv, https://www.medrxiv.org/content/10.1101/2021.08.02.21260750v1, https://c19p.org/bhatt
Small retrospective database analysis of 37 late stage patients hospitalized in an intensive care center in China, not finding a significant difference in viral shedding. Pateints were all in serious condition. There was only one death however the group is not specified. Confounding by indication is likely.
Jan 2021, Research Square, https://www.researchsquare.com/article/rs-119202/v1, https://c19p.org/li2
Small late stage (7-10 days post symptoms) study of nasal swab RNA with 12 control and 33 patients, showing no significant differences (significant reduction in viral load is seen in both groups). The groups are not comparable, with significant differences seen between hospitalized and non-hospitalized patients. 9 of 10 hospitalized patients were in the HCQ group and only one in the control group. 2 additional control patients were added between the first and second version of this preprint (including the only hospitalized control patient).
Jun 2020, medRxiv, https://www.medrxiv.org/content/10.1101/2020.06.30.20143289v1, https://c19p.org/komissarov
Retrospective 459 SLE, RA, SjS, or PsA patients in France, showing no significant difference with HCQ treatment. However, the statistical analysis shows significant mismatches with prior research, which may be due to overfitting with the limited data and very small number of events. For example, the analysis estimates lower risk OR 0.72 for age, and shows very different relative risks of SLE, RA, SjS, or PsA compared to other research. We note the very different distribution of diseases in the groups, for example there is a much higher prevalence of PsA in the no HCQ group. The inaccurate estimations of risk for the different diseases and for age likely makes the adjusted analysis very inaccurate.
Sep 2021, Rheumatology and Therapy, https://link.springer.com/10.1007/s40744-021-00373-1, https://c19p.org/guillaume
Retrospective analysis of seven databases in the USA, showing higher mortality with treatment. Results contradict strong evidence from the RECOVERY/SOLIDARITY trials, suggesting substantial confounding by indication. Time based confounding is very likely because HCQ became highly controversial and usage dramatically declined over the time covered, while overall treatment protocols during this period improved dramatically, i.e., more control patients likely come later in the period when treatment protocols were greatly improved. This study includes anyone PCR+ during or prior to their visit, and anyone with ICD-10 COVID-19 codes which includes asymptomatic PCR+ patients, therefore some patients in the control groups may be asymptomatic with regards to SARS-CoV-2, but in the hospital for another reason. Authors do not mention the possibility of any of these likely confounding factors.
Mar 2021, PLoS ONE, https://journals.plos.org/plosone/article?id=10.1371/journal.pone.0248128, https://c19p.org/stewart
Retrospective database analysis of chronic HCQ users and matched control patients, failing to match or adjust for the very different baseline risk for systemic autoimmune disease patients. Other research shows that the risk of COVID-19 for systemic autoimmune disease patients is much higher overall, Ferri et al. show OR 4.42, p<0.001 [Ferri].
Mar 2021, Eurosurveillance, https://www.eurosurveillance.org/content/10.2807/1560-7917.ES.2021.26.9.2001202, https://c19p.org/vivancohidalgo
RCT 254 very late stage (93% on oxygen, 17% in ICU at baseline) hospitalized patients in Saudi Arabia not showing significant differences with HCQ+favipiravir treatment. Only SaO2 < 94% patients were eligible, however the actual SaO2 of enrolled patients is not provided.
Apr 2021, Infect. Dis. Ther., https://link.springer.com/epdf/10.1007/s40121-021-00496-6, https://c19p.org/bosaeed
Retrospective 150 patients in the Dominican Republic, 132 treated with HCQ, showing higher mortality with treatment in unadjusted results. Confounding by indication is likely.
Dec 2020, medRxiv, https://www.medrxiv.org/content/10.1101/2020.12.11.20247437v1, https://c19p.org/deluna
HCQ+AZ early in the epidemic had a fairly good success rate with few complications, 86% of HCQ patients survived and 92% of HCQ+AZ patients. Patients not receiving either had 93% survival but were not considered comparable because the treated groups were significantly more ill (100% hypoxic at admission vs. 59%) and this study does not adjust for the differences. Transition from an early intubation strategy to aggressive utilization of high flow nasal cannula and noninvasive ventilation (i.e, BiPAP) was successful in freeing up ICU resources.
Jul 2020, medRxiv, https://www.medrxiv.org/content/10.1101/2020.07.17.20156521v1, https://c19p.org/mcgrail
Small retrospective study with 63 patients (32 treated with HCQ), showing no effectiveness, however the baseline state of each arm significantly differs. This preprint was submitted to NEJM but has not been published several months later.
Apr 2020, Preprint, https://www.sefq.es/_pdfs/NEJM_Hydroxychlorquine.pdf, https://c19p.org/barbosa
Retrospective 202 patients in Saudi Arabia not showing significant differences with treatment. No information is provided on how patients were selected for treatment, there may be significant confounding by indication. Time varying confounding is also likely as HCQ became controversial during the period studied, therefore HCQ use was likely more frequent toward the beginning of the period, a time when overall treatment protocols were significantly worse.
Dec 2020, Turk. Thorac. J., https://turkthoracj.org/en/use-of-hydroxychloroquine-in-patients-with-covid-19-a-retrospective-observational-study-131729, https://c19p.org/lotfy
Retrospective 559 COVID-19 ICU patients in Indonesia, showing no difference in mortality with HCQ in unadjusted results.
Sep 2023, PLOS ONE, https://journals.plos.org/plosone/article?id=10.1371/journal.pone.0290964, https://c19p.org/burhan
Retrospective 395 hospitalized patients in Brazil, showing higher mortality with HCQ treatment, without statistical significance.
May 2022, Frontiers in Cellular and Infection Microbiology, https://www.frontiersin.org/articles/10.3389/fcimb.2022.899702/full, https://c19p.org/silva3
Retrospective 1,500 hospitalized late stage (median SaO2 87.7) patients in Turkey, showing no significant difference with HCQ treatment.
Apr 2021, Respiratory Medicine, https://www.sciencedirect.com/science/article/pii/S0954611121001396, https://c19p.org/kokturk
Retrospective cancer patients, showing adjusted OR 1.03 [0.62-1.73] for HCQ. The study reports the number of HCQ+AZ patients but they do not provide results for HCQ+AZ (only HCQ + any other treatment). Significant confounding by indication and compassionate use is likely.
Jul 2020, Cancer Discovery, https://cancerdiscovery.aacrjournals.org/content/early/2020/09/12/2159-8290.CD-20-0941, https://c19p.org/rivera
37 patient HCQ late treatment study: 29% worse viral clearance (p=0.7).
2 very small studies with hospitalized patients in Taiwan. RCT with 21 treatment and 12 SOC patients. No mortality, or serious adverse effects. Median time to negative RNA 5 days versus 10 days SOC, p=0.4. Risk of PCR+ at day 14, RR 0.76, p = 0.71. Small retrospective study with 12 of 28 HCQ patients and 5 of 9 in the control group being PCR- at day 14, RR 1.29, p = 0.7. The RCT and retrospective study are listed separately [Chen, Chen].
Jul 2020, PLoS ONE, https://journals.plos.org/plosone/article?id=10.1371/journal.pone.0242763, https://c19p.org/chen26
Observational study of 181 patients with advanced disease requiring oxygen showing no benefit for HCQ. Power of study appears too low to support conclusions [bmj.com]. None of the 15 patients receiving HCQ+AZ were transferred to intensive care or died compared to 23% overall.
May 2020, BMJ 2020, https://www.bmj.com/content/369/bmj.m1844, https://c19p.org/mahevas
Retrospective observational late stage study showing no significant differences but calling for clinical trials. Zervos et al. [ijidonline.com] point out serious limitations that they say should be corrected on the record: patients receiving HCQ with or without AZ were overall sicker on presentation and had multiple other risk factors including much higher risk based on ethnicity; patients receiving HCQ were more likely to be obese, diabetic, have chronic lung disease, and cardiovascular conditions; yet these sicker patients had approximately the same mortality rates compared to patients with a milder course of the disease and less risk factors. However, the authors conclude that "there are no significant benefits." It is noteworthy that HCQ was associated with a significant survival benefit in a larger cohort of patients from New York City as reported by [Mikami]. See also [worldtribune.com].
May 2020, JAMA, May 11, 2020, https://jamanetwork.com/journals/jama/fullarticle/2766117, https://c19p.org/rosenberg
Retrospective 217 critically ill patients, 114 receiving HCQ, showing no significant difference in mortality.
Apr 2020, Critical Care Medicine, https://journals.lww.com/ccmjournal/Fulltext/2020/09000/ICU_and_Ventilator_Mortality_Among_Critically_Ill.35.aspx, https://c19p.org/auld
Retrospective 7,580 hospitalized patients in Brazil, showing longer hospitalization, and no significant difference in mortality, mechanical ventilation, and ICU admission with HCQ treatment. Authors note confounding by indication due to selected use in a compassionate use context. Authors match only on age, sex, cardiovascular comorbidities, and in-hospital use of corticosteroid, and only 10% of patients received HCQ/CQ, therefore confounding by indication is likely to be significant. A different matching list is included in the text, but neither includes COVID-19 severity. In the first line of the abstract authors falsely state that there is no evidence of benefit for HCQ treatment. While misrepresenting prior research is common, this is an extreme case and raises concern for validity of the analysis. In reality controlled studies show statistically significant positive results for one or more outcomes (including RCTs). Authors discussion of prior research shows similar bias.
Sep 2023, Arquivos Brasileiros de Cardiologia, https://abccardiol.org/article/dados-de-vida-real-sobre-o-uso-da-hidroxicloroquina-ou-da-cloroquina-combinadas-ou-nao-a-azitromicina-em-pacientes-com-covid-19-uma-analise-retrospectiva-no-brasil/, https://c19p.org/souzasilva
Retrospective database analysis with 17 cases for existing HCQ users and 5 severe cases, showing no significant difference for cases and higher risk for severe cases. However, HCQ users are likely systemic autoimmune disease patients and authors do not adjust for the very different baseline risk for these patients. Other research shows that the risk of COVID-19 for systemic autoimmune disease patients is much higher overall, Ferri et al. show OR 4.42, p<0.001 [Ferri].
Dec 2020, Int. J. Infectious Diseases, https://www.sciencedirect.com/science/article/pii/S1201971220325650, https://c19p.org/huh2
325 patient HCQ late treatment study: 890% higher progression (p=0.03).
Retrospective 325 hospitalized COVID-19 patients in Malaysia, showing higher progression with HCQ, however the groups are not comparable. 17 HCQ vs. 3 control patients had severity category ≥3 at baseline (7 vs. 0 for severity ≥4).
Mar 2023, Malaysian J. Medicine and Health Sciences, https://medic.upm.edu.my/upload/dokumen/2023032211275502_MJMHS_0551.pdf, https://c19p.org/ho2
Retrospective 340 patients with hematological malignancy in Turkey, showing higher mortality with HCQ treatment. Confounding by time is likely because more HCQ patients were earlier in time when overall treatment protocols were significantly worse.
Sep 2021, Turk. J. Haematol., https://pubmed.ncbi.nlm.nih.gov/34521187/, https://c19p.org/civrizbozdag
Retrospective hospitalized patients in Saudi Arabia, showing lower mortality with favipiravir compared to HCQ, not quite reaching statistical significance. Authors do not indicate the factors behind which therapy was chosen. May be subject to significant confounding by indication and confounding by time.
Sep 2021, Int. J. General Medicine, https://www.dovepress.com/getfile.php?fileID=73585, https://c19p.org/alotaibi
Retrospective 188 hospitalized patients in Brazil, showing higher risk of mortality with HCQ. Relatively few patients received HCQ. The results are likely subject to confounding by indication with treatment more likely for severe cases, and severity was not used in adjustments. Confounding by time is likely, with declining use of HCQ and improving SOC over the study period.
Jul 2021, Diabetology & Metabolic Syndrome, https://dmsjournal.biomedcentral.com/articles/10.1186/s13098-021-00695-8, https://c19p.org/tamurah
203 hospitalized patients in France, not showing significant differences with treatment. Confounding by indication is likely. Authors do not discuss confounding.
Jun 2021, PLOS ONE, https://journals.plos.org/plosone/article?id=10.1371/journal.pone.0252388, https://c19p.org/saib
Retrospective 1,108 hospitalized patients in New York showing significantly higher mortality with HCQ treatment. Time based confounding is very likely because HCQ became increasingly controversial and less used over the time covered (Mar - Jun 2020), while overall treatment protocols during this period improved dramatically, i.e., more control patients likely come later in the period when treatment protocols were greatly improved. Authors note that for every week or month later that a person was admitted, their risk of death dropped by 16% and 49%, respectively, yet they do not consider time based confounding.
May 2021, PLOS One, https://journals.plos.org/plosone/article?id=10.1371/journal.pone.0251262, https://c19p.org/sammartino
Retrospective 3,345 hospitalized patients in India, 11.5% treated with HCQ, showing unadjusted higher mortality with treatment. Confounding by indication and time based confounding (due to declining use over the period when overall treatment protocols improved dramatically) are likely.
Apr 2021, Clinical Epidemiology and Global Health, https://www.sciencedirect.com/science/article/pii/S2213398421000555, https://c19p.org/mohandas
Retrospective database analysis of 1,669 patients in the US showing OR 1.81, p = 0.01. Confounding by indication is likely. COVID-19 was determined via PCR+ results, therefore authors include patients asymptomatic for COVID-19, but in the hospital for other reasons. While authors adjust for severity, the method used is very poor. 93.5% of patients are classified as "mild", which is patients with no documented care in a critical care unit within 8 hours of admission. Therefore almost all patients are in the same category, and those in a different category may be due to symptoms unrelated to COVID-19. Lower bias toward male patients in the control group also agrees with the hypothesis that the control group is made up of more people that were in hospital for another reason. Since the analysis covers the initial period of the pandemic in the USA, it is likely that HCQ was used more often earlier in the analysis period when treatment protocols were considerably worse. It's..
Dec 2020, Int. J. Infectious Diseases, https://www.sciencedirect.com/science/article/pii/S1201971220325832, https://c19p.org/sands
Retrospective 67 hospitalized patients in the USA showing non-statistically significant unadjusted increased mortality with HCQ. Confounding by indication is likely. Time varying confounding is likely. HCQ became controversial and was suspended during the end of the period studied, therefore HCQ use was likely more frequent toward the beginning of the study period, a time when overall treatment protocols were significantly worse.
Dec 2020, Open Forum Infectious Diseases, https://academic.oup.com/ofid/article/7/Supplement_1/S330/6057008, https://c19p.org/psevdos
Retrospective 161 hospitalized patients in the USA showing non-statistically significant unadjusted increased mortality with HCQ. Confounding by indication is likely. Time varying confounding is likely. HCQ became controversial and was suspended towards the end of the period studied, therefore HCQ use was likely more frequent toward the beginning of the study period, a time when overall treatment protocols were significantly worse.
Dec 2020, Open Forum Infectious Diseases, https://academic.oup.com/ofid/article/7/Supplement_1/S251/6058327, https://c19p.org/teixeira
WHO SOLIDARITY open-label trial with 954 very late stage (64% on oxygen/ventilation) HCQ patients, mortality relative risk RR 1.19 [0.89-1.59], p=0.23. HCQ dosage very high as in RECOVERY, 1.6g in the first 24 hours, 9.6g total over 10 days, only 25% less than the high dosage that Borba et al. show greatly increases risk (OR 2.8) [Borba]. Authors state they do not know the weight or obesity status of patients to analyze toxicity (since they do not adjust dosage based on patient weight, toxicity may be higher in patients of lower weight). KM curves show a spike in HCQ mortality days 5-7, corresponding to ~90% of the total excess seen at day 28 (a similar spike is seen in the RECOVERY trial). Almost all excess mortality is from ventilated patients. Authors refer to a lack of excess mortality in the first few days to suggest a lack of toxicity, but they are ignoring the very long half-life of HCQ and the dosing regimen - much higher levels of HCQ will be reached later. Increased..
Oct 2020, SOLIDARITY Trial Consortium, NEJM, https://www.nejm.org/doi/full/10.1056/NEJMoa2023184, https://c19p.org/solidarity
Survey of 319 autoimmune disease patients taking CQ/HCQ with 5.3% COVID-19 incidence, compared to a control group from the general population (matched on age, sex, and region, but not adjusted for autoimmune disease), with 3.4% incidence. It not clear why authors did not compare with autoimmune patients not on CQ/HCQ. Other research shows that the risk of COVID-19 for systemic autoimmune disease patients is much higher overall, Ferri et al. show OR 4.42, p<0.001 [Ferri], which is the observed real-world risk, taking into account factors such as these patients potentially being more careful to avoid exposure. If we adjust for the different baseline risk, the result becomes RR 0.36, p<0.001, suggesting a substantial benefit for HCQ/CQ treatment (as shown in other studies). There may also be significant survey bias - those experiencing COVID-19 may be more likely to respond to the survey. Authors note that they "could not eliminate completely the possibility of some bias due to the..
Sep 2020, PLOS ONE, https://journals.plos.org/plosone/article?id=10.1371/journal.pone.0243598, https://c19p.org/laplana
Retrospective 82 hospitalized patients HCQ/AZ, 52 SOC, not finding statistically significant differences. Confounding by indication - authors note that the HCQ/AZ patients were more severely ill, and do not attempt to adjust for confounders.
Jul 2020, British J. Clinical Pharmacology, https://bpspubs.onlinelibrary.wiley.com/doi/full/10.1111/bcp.14482, https://c19p.org/kelly
Analysis of 144 hospitalized kidney transplant patients showing HCQ mortality HR 1.53, p = 0.17. Subject to confounding by indication.
Jul 2020, American J. Transplantation, https://onlinelibrary.wiley.com/doi/full/10.1111/ajt.16185, https://c19p.org/cravedi
Retrospective 928 cancer patients, showing HCQ OR 1.06 [0.51-2.20]. HCQ+AZ OR 2.93 [1.79-4.79]. The relative risks of different therapies suggest that the results are overly affected by confounding by indication. Authors note: HCQ+AZ might not be the cause of increased mortality, but instead these were given to patients with more severe COVID-19.
May 2020, Lancet, June 20, 2020, https://www.thelancet.com/journals/lancet/article/PIIS0140-6736(20)31187-9/fulltext, https://c19p.org/kuderer
262 patient HCQ prophylaxis study: 17% higher mortality (p=0.8), 78% higher combined mortality/ICU admission (p=0.21), and 45% higher hospitalization (p=0.12).
Retrospective 71 chronic HCQ patients compared with 191 matched controls, analyzing only those with a highly suspected or confirmed diagnosis of COVID-19. No significant difference was found in outcomes, however matching failed with extreme confounding - 77.5% of HCQ patients with systemic autoimmune diseases vs. 21.5% of control patients. Other research shows that the risk of COVID-19 for systemic autoimmune disease patients is much higher overall, Ferri et al. show OR 4.42, p<0.001 [Ferri].
Jan 2021, Revue du Rhumatisme, https://www.sciencedirect.com/science/article/abs/pii/S1169833021002489, https://c19p.org/trefond
RECOVERY trial finds no significant benefit for very late stage (9 days after symptom onset) very sick patients. Results may be due to the unusually high dosage used (9.2g total over 10 days) [twitter.com, twitter.com]. The overall dosage used is only 23% less than the high dosage that Borba et al. show greatly increases risk (OR 2.8) [Borba]. Authors do not report results based on weight, BMI, or related conditions such as diabetes, which may provide additional evidence of toxic dosages. Authors do not adjust dosage based on patient weight, so toxicity may be higher in patients of lower weight. KM curves show a spike in HCQ mortality days 5-8, corresponding to ~85% of the total excess seen at day 28 (a similar spike is seen in the SOLIDARITY trial). Authors note: "we did not observe excess mortality in the first 2 days of treatment ... when early effects of dose-dependent toxicity might be expected", but they are ignoring the very long half-life of HCQ and the dosing..
Jun 2020, RECOVERY Collaborative Group, NEJM, https://www.nejm.org/doi/full/10.1056/NEJMoa2022926, https://c19p.org/recovery
Retrospective 2,200 healthcare workers in India, 996 taking HCQ prophylaxis, showing no significant differences. There were large differences in the occupation of participants and therefore exposure, and the authors make no adjustments.
Jan 2022, J. Basic and Clinical Physiology and Pharmacology, https://www.degruyter.com/document/doi/10.1515/jbcpp-2021-0221/html, https://c19p.org/juneja
This paper has inconsistent values - the number of treatment and control patients differs in the text and Table 1, we have used treatment 188 and control 148. Retrospective 336 hospitalized patients in the USA showing higher mortality, ICU admission, and intubation with treatment. Confounding by indication is likely. Time varying confounding is also likely due to declining usage over the early period when overall treatment protocols were also improving dramatically. Authors and reviewers appear to be unfamiliar with either of these.
Feb 2021, American J. Health-System Pharmacy, https://academic.oup.com/ajhp/advance-article/doi/10.1093/ajhp/zxab056/6144083, https://c19p.org/awad
Retrospective 317 HCQ users and 333 household contacts, showing higher risk with HCQ.
Mar 2022, J. Medical Virology, https://onlinelibrary.wiley.com/doi/10.1002/jmv.27731, https://c19p.org/oztas
Retrospective 1,769 hospitalized patients in the USA showing no significant differences for HCQ, and higher intubation for HCQ+AZ.
Jun 2021, American J. Epidemiology, https://academic.oup.com/aje/advance-article/doi/10.1093/aje/kwab183/6308675, https://c19p.org/gerlovin
Retrospective 11 critically ill COVID-19 ICU patients with organ failure treated with camostat mesylate (6 patients) or HCQ (5 patients). Over an 8 day period, the severity of COVID-19 decreased in the camostat group as measured by a decline in the SOFA score, inflammatory markers, and improvement in oxygenation. A similar effect was not seen in the HCQ group.
Nov 2020, Critical Care Explorations, https://journals.lww.com/10.1097/CCE.0000000000000284, https://c19p.org/hofmannwinklerh
Retrospective 230 low risk healthcare workers taking HCQ prophylaxis, and 106 that declined, showing higher cases without statistical significance. No case severity information is provided. The point estimate favored HCQ when excluding the first 14 days and including participants that worked for at least 16 days. Authors note a significant dose response relationship.
Dec 2022, Life, https://www.mdpi.com/2075-1729/12/12/2047, https://c19p.org/shahrin
290 patient observational trial in the USA, not showing a significant difference with HCQ treatment overall, but showing significantly lower mortality in a subgroup of patients where HCQ is expected to be beneficial based on a machine learning algorithm.
Nov 2020, J. Clinical Medicine, https://www.mdpi.com/2077-0383/9/12/3834, https://c19p.org/burdick
Retrospective 228 rheumatic disease and 228 non-rheumatic disease hospitalized COVID-19 patients in Spain, showing higher risk of severe COVID-19 with HCQ treatment.
Aug 2020, Annals of the Rheumatic Diseases, https://ard.bmj.com/lookup/doi/10.1136/annrheumdis-2020-218296, https://c19p.org/pablos
Small retrospective database analysis of 36 patients receiving HCQ not showing significant differences. Confounding by indication is likely.
Aug 2020, J. Global Antimicrobial Resistance, https://www.sciencedirect.com/science/article/pii/S2213716520301934, https://c19p.org/kalligeros
Very small retrospective analysis of 34 patients finding slower binary PCR viral clearance with HCQ. No information on severity for treatment versus control is provided. No deaths, ICU admission, or mechanical ventilation. Binary PCR does not distinguish replication-competence. HCQ treatment started very late for many patients with >= 9 days for 25%.
May 2020, Medicine, https://journals.lww.com/md-journal/Fulltext/2020/12240/Hydroxychloroquine_is_associated_with_slower_viral.34.aspx, https://c19p.org/mallat
Low-dose prophylaxis RCT with low-risk healthcare workers in India, showing no significant differences. Symptomatic case results are not provided. Followup was over 6 months, however treatment ended after 3 months. 21% of patients discontinued treatment before 3 months (Table S2).
May 2022, BMJ Open, https://bmjopen.bmj.com/lookup/doi/10.1136/bmjopen-2021-059540, https://c19p.org/tirupakuzhi
Retrospective 230 hospitalized patients in Brazil showing higher mortality with HCQ treatment. Authors note that the treatments were more likely to be offered to sicker patients. Authors note that they do not know if treatment was started before or after ICU admission and intubation. Dosage is unknown.
Nov 2021, Revista da Associação Médica Brasileira, https://www.scielo.br/j/ramb/a/kzbmDvJqjJdQR9GfqK65CZs/, https://c19p.org/ferreira2h
Delayed publication of an early terminated late treatment RCT with low-risk (no mortality) outpatients in the USA, showing no significant differences with HCQ. Authors do not provide symptom onset data, but the subgroup analysis suggests that more patients may have been in the 5+ days group (the estimate for the 5+ days group has a smaller confidence interval, and the overall mean/median for HCQ is much closer to the 5+ days group). Treatment was started one day after enrollment according to Table S1 (authors report "commonly 1 day after randomization" in the text). This suggests that most patients were treated 6+ days after onset. Subgroup analysis for <5, ≥5 days is provided only for viral shedding duration, and shows improved results for earlier treatment. Adherence was only 66% (Figure 1). Publication was 21 months after the trial ended. Registered outcomes were modified November 2022, December 2022, and January 2023, all over a year after completion of the trial. For..
Mar 2023, Microbiology Spectrum, https://journals.asm.org/doi/10.1128/spectrum.04674-22, https://c19p.org/spivak
Retrospective 1,106 prostate cancer patients, showing higher mortality with HCQ treatment.
Nov 2021, JAMA Network Open, https://jamanetwork.com/journals/jamanetworkopen/fullarticle/2786026, https://c19p.org/schmidth
Early terminated PEP RCT comparing HCQ and vitamin C with 781 low-risk patients (83% household contacts), reporting no significant differences. Different results were reported at IDWeek from the AIM results. The study enrolled people with their last exposure within 4 days, i.e., if someone was exposed for 30 days in a row, they could be enrolled anywhere from day 1 to day 34. Therefore many were likely infected earlier than the enrollment date. Note that PCR has a very high false negative rates, e.g., 100% on day 1 and 67% on day 4 here [ncbi.nlm.nih.gov]. 50% of infections were detected by day 4. With the PCR false negatives and treatment delays it is likely that a majority of infections happened before enrollment or before HCQ can reach therapeutic levels. Significantly more cases were caught at baseline in the control group (54 vs. 29 for HCQ) and excluded from analysis. The early presentation stated that therapy started one day after enrollment and study supplies were sent to the..
Dec 2020, Annals of Internal Medicine, https://www.acpjournals.org/doi/10.7326/M20-6519, https://c19p.org/barnabas
Early terminated very late stage (65% on supplemental oxygen) RCT with 242 HCQ and 237 control patients showing no significant difference in outcomes. For the subgroup not on supplemental oxygen at baseline (relatively early treatment), the odds ratio for the 7 point outcome scale is: aOR 0.61 [0.34-1.08]. Dosage may be too low: Dose in first 24 hours - 1g (compare to Boulware et al. 2g) Dose in 5 days - 2.4g (compare to Boulware et al. 3.8g) Dosage note: Boulware 2g within 24 hours includes the second day dose. Note two important differences with the RECOVERY/SOLIDARITY dosage which is believed to be dangerously high - in RECOVERY/SOLIDARITY the total dose is much higher, which is problematic because the half-life of HCQ is very long, and it is given to patients that are already in very serious condition. Note the paper reports primary outcome values with OR>1 favoring HCQ, we have converted to OR<1 favoring HCQ. Subgroup analysis is in the supplemental appendix.
Nov 2020, JAMA, https://jamanetwork.com/journals/jama/fullarticle/2772922, https://c19p.org/self
Small RCT on very late stage use of HCQ, with 48% on oxygen at baseline. 67 HCQ patients, 61 control. Baseline states were not comparable - 82% more HCQ patients had the highest severity at baseline, there was 32% more male HCQ patients, and 44% more control patients used AZ. The HCQ group also had significantly more patients with cerebrovascular disease, cardiovascular disease (non-hypertension), renal disease (non-dialysis), and a history of organ transplants.
Sep 2020, Open Forum Infectious Diseases, https://academic.oup.com/ofid/advance-article/doi/10.1093/ofid/ofaa446/5910201, https://c19p.org/ulrich
Retrospective 1,472 hospitalized patients in Turkey, showing a higher risk of ICU admission and ventilation with HCQ, without statistical significance.
Aug 2022, Frontiers in Medicine, https://www.frontiersin.org/articles/10.3389/fmed.2022.894126/full, https://c19p.org/babayigith
Small RCT with 61 patients in Nigeria, all patients treated with ivermectin, zinc, and vitamin C, showing no significant improvements in recovery with the addition of HCQ+AZ.
Sep 2021, J. Infectious Diseases and Epidemiology, https://www.clinmedjournals.org/articles/jide/journal-of-infectious-diseases-and-epidemiology-jide-7-233.php?jid=jide, https://c19p.org/babalola2h
Small PrEP RCT of low risk healthcare workers, showing no significant differences. Authors report that there was no hospitalization, ICU care, or death from COVID-19, however table 3 of the preprint shows severe events labeled as "requiring hospitalization". Symptomatology and disease severity results in tables 3 and 4 appear inconsistent. NCT04359537.
May 2021, Cureus, https://www.cureus.com/articles/77806-pre-exposure-prophylaxis-with-various-doses-of-hydroxychloroquine-among-healthcare-personnel-with-high-risk-exposure-to-covid-19-a-randomized-controlled-trial, https://c19p.org/syed
Planned RCT of HCQ vs. HCQ+nitazoxanide which was aborted due to the retracted Surgisphere paper. Authors retrospectively analyze a small set of HCQ vs. nitazoxanide patients (which were protocol deviations in the planned RCT), showing reduced hospitalization time and ICU admission with nitazoxanide.
Nov 2021, PAMJ - Clinical Medicine, https://www.clinical-medicine.panafrican-med-journal.com/content/article/7/15/full/, https://c19p.org/calderon2h
RCT 84 low risk patients, 42 treated with HCQ/AZ, showing no significant differences. There was only one hospitalization which was in the treatment arm.
Aug 2021, Int. J. Antimicrobial Agents, https://www.sciencedirect.com/science/article/pii/S0924857921002065, https://c19p.org/rodrigues
Early terminated healthcare worker PrEP RCT with only 68 patients and 8 cases, showing no significant difference with HCQ. No information on symptoms per group, case severity, or the timing of cases is provided.
Feb 2023, BMC Research Notes, https://bmcresnotes.biomedcentral.com/articles/10.1186/s13104-023-06281-7, https://c19p.org/llanoscuentas
Long-term followup for the REMAP-CAP very late stage ICU trial, showing higher risk with HCQ, not quite reaching statistical significance.
Dec 2022, JAMA, https://jamanetwork.com/journals/jama/fullarticle/2799870, https://c19p.org/higgins
Small RCT in Norway showing no significant differences with HCQ treatment. Add-on trial to WHO Solidarity.
Jul 2021, Annals of Internal Medicine, https://www.acpjournals.org/doi/10.7326/M21-0653, https://c19p.org/barratdue
Small early terminated late treatment RCT showing no significant differences. The HCQ group was a median of 7 days from symptom onset at baseline, which may not include the delay delivering the medication. From the 4 HCQ hospitalizations, only one is in the per-protocol analysis, and that patient was hospitalized one day after randomization (authors do not specify if the patient received and took any HCQ before the hospitalization). The trial was terminated early due to the fraudulent Lancet article (wording here is notably different between the submitted and published versions). Per-protocol analysis, the submitted version, and the peer-review comments (two reviewers, only one with substantial feedback) are in the supplementary material. Long-term recovery results are reported in [Ganesh]. When a patient reported a symptom, they were asked whether they were still experiencing that symptom, and to choose between these three options when comparing the symptom to their pre-COVID-19..
Jun 2021, CMAJ Open, http://cmajopen.ca/content/9/2/E693.full, https://c19p.org/schwartz2
Early terminated very late stage (99% on oxygen, 81% in ICU, 18% on mechanical ventilation at baseline) RCT with 24 CQ patients, 29 HCQ, and 52 control patients, showing worse clinical outcomes with treatment. NCT04420247.
Apr 2021, Scientific Reports, https://www.nature.com/articles/s41598-021-88509-9, https://c19p.org/reanato
1. Schilling et al., Evaluation of hydroxychloroquine or chloroquine for the prevention of COVID-19 (COPCOV): A double-blind, randomised, placebo-controlled trial
4,652 patient HCQ prophylaxis RCT: 57% fewer symptomatic cases (p=0.0002).RCT 4,652 low-risk participants, published days after completion, showing significantly lower PCR+ COVID-19 cases with HCQ/CQ prophylaxis, p = 0.0004. Authors include a meta-analysis of this and 11 other RCTs confirming significantly lower COVID-19 cases. Authors conclude that HCQ/CQ could have been deployed with benefit early in the pandemic. HCQ/CQ was well tolerated with no serious drug-related adverse events. There were significantly fewer severe adverse events with treatment. (Serious adverse events refer to serious outcomes while severe adverse events refer to intensity, e.g., severe headache). Authors note that "the primary outcome was subsequently changed to include seroconversion" rather than only PCR+ cases. The date of this change is not reported. The PCR+ results are the most reliable. Inclusion of seroconversion means that participants with asymptomatic COVID-19 and symptomatic non-COVID-19 infections will be counted as symptomatic COVID-19 cases...
Sep 2024, PLOS Medicine, https://journals.plos.org/plosone/article?id=10.1371/journal.pmed.1004428, https://c19p.org/schilling3
HCQ early treatment study: 85% lower progression (p=0.006), 24% faster improvement (p=0.02), and 36% improved viral clearance (p=0.001).
85% lower disease progression with early use of HCQ. Retrospective 616 patients in China showing adjusted progression HR 0.15, p = 0.006.
Dec 2020, BioScience Trends, https://www.jstage.jst.go.jp/article/bst/advpub/0/advpub_2020.03340/_article/-char/ja/, https://c19p.org/su
754 patient HCQ late treatment RCT: 66% improved viral clearance (p<0.0001).
RCT 754 patients comparing HCQ+AZ along with other treatment groups using lopinavir/ritonavir and doxycycline to a control group taking AZ, finding significantly faster viral clearance with all treatment groups. (The labels in Figure 2 appear to be reversed).
Feb 2021, Biochemistry Research Int., https://www.hindawi.com/journals/bri/2021/6685921/, https://c19p.org/purwati
4. Sulaiman et al., The Effect of Early Hydroxychloroquine-based Therapy in COVID-19 Patients in Ambulatory Care Settings: A Nationwide Prospective Cohort Study
7,892 patient HCQ early treatment study: 64% lower mortality (p=0.01), 44% lower combined mortality/ICU admission (p=0.02), 37% lower ICU admission (p=0.13), and 39% lower hospitalization (p<0.0001).Observational prospective 5,541 patients, adjusted HCQ mortality odds ratio OR 0.36, p = 0.012. Adjusted hospitalization OR 0.57, p < 0.001. Zinc supplementation was used in all cases. Early treatment in ambulatory fever clinics in Saudi Arabia.
Sep 2020, medRxiv, https://www.medrxiv.org/content/10.1101/2020.09.09.20184143v1, https://c19p.org/sulaiman
5. Seet et al., Positive impact of oral hydroxychloroquine and povidone-iodine throat spray for COVID-19 prophylaxis: an open-label randomized trial
1,051 patient HCQ prophylaxis RCT: 35% fewer symptomatic cases (p=0.05) and 32% fewer cases (p=0.009).Prophylaxis RCT in Singapore with 3,037 low risk patients, showing lower serious cases, lower symptomatic cases, and lower confirmed cases of COVID-19 with all treatments (ivermectin, HCQ, PVP-I, and Zinc + vitamin C) compared to vitamin C. Only 71.4% reported >70% adherence, limiting efficacy. QTc did not statistically significantly differ between baseline and follow-up readings (mean 379 vs 378ms, paired t-test p=0.387). Meta-analysis of vitamin C in 6 previous trials shows a benefit of 16%, so the actual benefit of ivermectin, HCQ, and PVP-I may be higher. Cluster RCT with 40 clusters. There were no hospitalizations and no deaths.
Apr 2021, Int. J. Infectious Diseases, https://www.ijidonline.com/article/S1201-9712(21)00345-3/fulltext, https://c19p.org/seeth
6. Simova et al., Hydroxychloroquine for prophylaxis and treatment of COVID-19 in health care workers
38 patient HCQ early treatment study: 94% lower hospitalization (p=0.01) and 96% improved viral clearance (p=0.001).100% reduction in hospitalization and cases with early treatment using HCQ+AZ+zinc. Brief report on healthcare workers in Bulgaria. 0 hospitalizations with treatment vs. 2 for control 0 PCR+ at day 14 with treatment vs. 3 for control 33 treatment patients and 5 control patients. No serious adverse events. This paper reports on both PEP and early treatment, we have separated the two studies.
Nov 2020, New Microbes and New Infections, https://www.sciencedirect.com/science/article/pii/S2052297520301657, https://c19p.org/simova
7. Tsanovska et al., Hydroxychloroquine (HCQ) treatment for hospitalized patients with COVID-19
140 patient HCQ late treatment PSM study: 58% lower mortality (p=0.03), 74% lower ventilation (p=0.0007), and 70% lower ICU admission (p=0.0004).PSM prospective study of 260 COVID-19 patients in Bulgaria, showing lower mortality, ventilation, and ICU admission with HCQ treatment.
Mar 2022, Infectious Disorders - Drug Targets, https://www.eurekaselect.com/article/121288, https://c19p.org/tsanovska
8. Yu et al., Beneficial effects exerted by hydroxychloroquine in treating COVID-19 patients via protecting multiple organs
2,882 patient HCQ late treatment study: 83% lower progression (p=0.05) and 85% lower mortality (p=0.02).Retrospective 2,882 patients in China, median age 62, 278 receiving HCQ, median 10 days post hospitalization, showing that HCQ treatment can reduce systemic inflammation and inhibit the cytokine storm, thus protecting multiple organs from inflammatory injuries, such as detoxification in the liver and attenuation of cardiac injury. IL-6 levels significantly reduced after HCQ treatment, p<0.05, and elevated after HCQ withdrawal. The significantly lower dose used here is potentially related to the different observations from the RECOVERY trial results. Authors suggest that treatment should be started as soon as possible. The 550 patients that were critically ill at baseline are reported in a separate paper. For the non-critically-ill patients at baseline, the proportion of patients that became critically ill was significantly lower for those treated with HCQ. For the subset of patients that started HCQ treatment early only 1.4% died versus 3.9% for HCQ started late and 9.1% for control..
Aug 2020, Science China Life Sciences, 2020 Aug 3, https://link.springer.com/article/10.1007/s11427-020-1782-1, https://c19p.org/yu2
9. Hong et al., Early Hydroxychloroquine Administration for Rapid Severe Acute Respiratory Syndrome Coronavirus 2 Eradication
90 patient HCQ early treatment study: 65% improved viral clearance (p=0.001).HCQ 1-4 days from diagnosis was the only protective factor against prolonged viral shedding found, OR 0.111, p=0.001. 57.1% viral clearance with 1-4 days delay vs. 22.9% for 5+ days delayed treatment. Authors report that early administration of HCQ significantly ameliorates inflammatory cytokine secretion and that COVID-19 patients should be administrated HCQ as soon as possible. 42 patients with HCQ 1-4 days from diagnosis, 48 with HCQ 5+ days from diagnosis.
Jul 2020, Infection & Chemotherapy, 2020, https://icjournal.org/DOIx.php?id=10.3947/ic.2020.52.3.396, https://c19p.org/hong
10. Chen et al., Efficacy of hydroxychloroquine in patients with COVID-19: results of a randomized clinical trial
62 patient HCQ late treatment RCT: 57% lower pneumonia (p=0.04).62 patients. RCT showing significantly faster recovery with HCQ. 13% progressed to severe cases in the control group, versus 0% for the treatment group. Significant improvement seen in pneumonia on chest CT for 61% of treated patients and 16% of control patients.
Mar 2020, medRxiv, https://www.medrxiv.org/content/10.1101/2020.03.22.20040758v3, https://c19p.org/chenrct
441 patient HCQ late treatment RCT: 24% lower hospitalization (p=0.57) and 4% improved viral clearance (p=0.1).
Early terminated RCT in Brazil showing lower mortality and hospitalization with HCQ, but not reaching statistical significance. Although the title includes "early treatment", treatment was relatively late, with most patients being over 5 days from the onset of symptoms. Adverse events were lower in the HCQ group compared to the control group. This trial appears to have been terminated at 45% enrollment while showing ≥70% probability of superiority. The futility threshold was not reported, but it would be highly unusual for it to be as high as 70% [doyourownresearch.substack.com]. The paper indicates the placebo was talc, however the trial protocol shows the "placebo" as vitamin C, for which there are 7 COVID-19 treatment studies as of April 2021 that collectively show significant efficacy. Results differ significantly from those reported prior to publication. Prior to publication, authors reported an RR for hospitalization or death of 1.0 [0.45-2.21] [ajtmh.org].
Apr 2021, JAMA Network Open, https://jamanetwork.com/journals/jamanetworkopen/fullarticle/2779044, https://c19p.org/reis
12. Million et al., Early Treatment with Hydroxychloroquine and Azithromycin in 10,429 COVID-19 Outpatients: A Monocentric Retrospective Cohort Study
10,429 patient HCQ early treatment study: 83% lower mortality (p=0.0007), 44% lower ICU admission (p=0.18), and 4% lower hospitalization (p=0.77).Retrospective 10,429 outpatients in France, 8,315 treated with HCQ+AZ a median of 4 days from symptom onset, showing significantly lower mortality with treatment.
May 2021, Reviews in Cardiovascular Medicine, https://www.imrpress.com/journal/RCM/22/3/10.31083/j.rcm2203116, https://c19p.org/million4
13. Chen et al., Efficacy and safety of chloroquine or hydroxychloroquine in moderate type of COVID-19: a prospective open-label randomized controlled study
48 patient HCQ late treatment RCT: 20% faster recovery (p=0.51) and 71% faster viral clearance (p=0.0004).RCT 48 hospitalized patients in China showing faster clinical recovery and viral clearance with CQ/HCQ.
Jun 2020, medRxiv, https://www.medrxiv.org/content/10.1101/2020.06.19.20136093v1, https://c19p.org/chen
14. Nasri et al., Efficacy of hydroxychloroquine in pre-exposure severe acute respiratory syndrome coronavirus 2 prophylaxis among high-risk healthcare workers: A multicenter study
143 patient HCQ prophylaxis RCT: 92% fewer symptomatic cases (p=0.03).RCT 143 healthcare workers in Iran, showing lower cases with HCQ prophylaxis, statistically significant only for moderate/severe cases. Baseline details are not provided.
Jan 2023, Advanced Biomedical Research, https://www.advbiores.net/article.asp?issn=2277-9175;year=2023;volume=12;issue=1;spage=3;epage=3;aulast=Nasri, https://c19p.org/nasri
864 patient HCQ late treatment study: 80% lower mortality (p<0.0001), 20% lower progression (p=0.43), and 31% faster viral clearance (p=0.26).
Retrospective 863 COVID-19 patients in Burkina Faso, showing lower mortality, lower progression for outpatients, and faster viral clearance with HCQ/CQ treatment. Only the lower mortality was statistically significant. NCT04445441.
Feb 2022, Int. J. Infectious Diseases, https://www.sciencedirect.com/science/article/pii/S1201971222001114, https://c19p.org/rouamba
16. Mitjà et al., A Cluster-Randomized Trial of Hydroxychloroquine as Prevention of Covid-19 Transmission and Disease
2,497 patient HCQ prophylaxis RCT: 46% lower mortality (p=0.39), 17% lower hospitalization (p=0.71), and 32% fewer cases (p=0.27).For positive symptomatic cases, a greater effect is seen for nursing home residents, RR=0.49 [0.21 - 1.17], vs. overall 0.89, possibly because the exposure events are identified faster in this context, versus home exposure where testing of the source may be more delayed. The trial is too small for significance here. If the trend continued this result would be significant at p<0.05 after about 25% more patients were added. There are 2 groups in this study: PCR+ at baseline (n=314) and PCR- at baseline (n=2000), which should be separated as they are different populations (primary outcome rates 18.6% and 22.2% compared to 3.0% and 4.3%). PCR+ already have COVID-19, so PEP analysis should be for the 2,000 PCR-, showing symptomatic COVID-19 of 4.3% (control) and 3.0% (treatment), RR 0.7, p=0.154. The paper has different RR values here, stating that they are adjusted for contact-level variables. It is not clear how they are computed - the adjusted RR for the overall sample is 4% lower, for..
Jul 2020, NEJM, https://www.nejm.org/doi/full/10.1056/NEJMoa2021801, https://c19p.org/mitjapep
17. Beltran Gonzalez et al., Efficacy and Safety of Ivermectin and Hydroxychloroquine in Patients with Severe COVID-19: A Randomized Controlled Trial
70 patient HCQ late treatment RCT: 63% lower mortality (p=0.27) and 25% lower progression (p=0.57).RCT late stage severe condition (93% SOFA ≥ 2, 96% APACHE ≥ 8) high comorbidity hospitalized patients in Mexico with 33 HCQ and 37 control patients not finding significant differences. NCT04391127.
Feb 2021, Infectious Disease Reports, https://www.mdpi.com/2036-7449/14/2/20, https://c19p.org/beltrangonzalezh
18. Rathod et al., Risk Factors associated with COVID-19 Patients in India: A Single Center Retrospective Cohort Study
565 patient HCQ early treatment study: 73% lower mortality (p=0.02).Retrospective 565 COVID-19 patients in India, showing lower mortality with HCQ+AZ treatment. Most patients (66%) had mild disease at baseline.
May 2023, The J. the Association of Physicians of India, https://pubmed.ncbi.nlm.nih.gov/37355843/, https://c19p.org/rathod2
100 patient HCQ early treatment study: 96% lower mortality (p=0.004).
Retrospective 100 COVID+ elderly nursing home patients, HCQ+AZ mortality 11.4% vs. control 61.9%, RR 0.18, p<0.001. Median age 85.
Sep 2020, European Geriatric Medicine, https://link.springer.com/article/10.1007/s41999-020-00432-w, https://c19p.org/heras
20. Bernabeu-Wittel et al., Effectiveness of a On-Site Medicalization Program for Nursing Homes with COVID-19 Outbreaks
272 patient HCQ early treatment study: 94% lower mortality (p=0.001).Retrospective 272 nursing home residents showing significantly improved survival after establishing a treatment program including HCQ with or without lopinavir/ritonavir and with the addition of adjuvant and antimicrobial treatments depending on circumstances. HCQ (114 patients), HCQ+LPV/RTV (18 patients), and HCQ+AZ (7 patients). Dosage details are in the supplementary appendix.
Jul 2020, J. Gerontol. A Biol. Sci. Med. Sci., https://academic.oup.com/biomedgerontology/advance-article/doi/10.1093/gerona/glaa192/5879759, https://c19p.org/bernabeuwittel
21. Novartis et al., Hydroxychloroquine Monotherapy and in Combination With Azithromycin in Patients With Moderate and Severe COVID-19 Disease
12 patient HCQ late treatment RCT: 71% lower mortality (p=0.42), 71% higher hospital discharge (p=0.42), 71% greater improvement (p=0.42), and 79% worse viral clearance (p=0.56).Early terminated RCT with only 20 patients.
Jul 2020, Novartis, NCT04358081, https://clinicaltrials.gov/study/NCT04358081, https://c19p.org/novartis
435 patient HCQ prophylaxis RCT: 51% fewer symptomatic cases (p=0.79) and 27% fewer cases (p=0.31).
Early terminated healthcare worker prophylaxis RCT in Spain, showing lower risk of symptomatic cases with HCQ prophylaxis, without statistical significance due to the small number of events.
Aug 2022, Clinical Microbiology and Infection, https://www.sciencedirect.com/science/article/pii/S1198743X22003706, https://c19p.org/polo
23. Dubee et al., Hydroxychloroquine in mild-to-moderate COVID-19: a placebo-controlled double blind trial
247 patient HCQ late treatment RCT: 46% lower mortality (p=0.21) and 26% lower combined mortality/intubation (p=0.48).Small early terminated late stage (60% on oxygen) RCT in France showing 46% lower mortality. mortality at 28 days relative risk RR 0.54 [0.21-1.42] combined mortality/intubation at 28 days relative risk RR 0.74 [0.33-1.70] If not stopped early and the same trend continued, statistical significance would be reached on 28 day mortality after ~550 patients (1,300 patients were planned). Mortality results are not provided for subgroups. For the subgroups receiving AZ: No safety concerns were identified. This study has been presented as negative, however the results do not support that conclusion.
Oct 2020, Clinical Microbiology and Infection, https://www.sciencedirect.com/science/article/pii/S1198743X21001403, https://c19p.org/dubee
24. Amaravadi et al., Hydroxychloroquine for SARS-CoV-2 positive patients quarantined at home: The first interim analysis of a remotely conducted randomized clinical trial
29 patient HCQ early treatment RCT: 60% improved recovery (p=0.13).Tiny early-terminated 34 patient RCT for outpatient treatment showing faster recovery with treatment (not statistically significant). All patients recovered (3 control patients recovered after crossover to the treatment arm) - as per protocol mid-recovery results have priority. There was no mortality and only one hospitalization on day 0 before treatment. There were no severe adverse events.
Feb 2021, medRxiv, https://www.medrxiv.org/content/10.1101/2021.02.22.21252228v1, https://c19p.org/amaravadi
25. Azhar et al., Effectiveness of early pharmaceutical interventions in symptomatic COVID-19 patients: A randomized clinical trial
471 patient HCQ early treatment RCT: 71% lower mortality (p=0.03), 4% greater improvement (p=0.64), and 10% improved viral clearance (p=0.52).RCT 471 mild COVID-19 patients in Pakistan showing no significant differences in clinical improvement and viral clearance between HCQ, azithromycin, oseltamivir, and combinations. Mortality was significantly lower in HCQ vs. non-HCQ arms. The best results for viral clearance and clinical improvement were seen with the combination of all treatments. There was no control group. No serious adverse events were reported. All patients had mild COVID-19 and the paper indicates early treatment, however time from onset is not reported and minimal baseline information is provided.
Mar 2024, Pakistan J. Medical Sciences, https://www.pjms.org.pk/index.php/pjms/article/view/8757, https://c19p.org/azhar
26. Derwand et al., COVID-19 Outpatients – Early Risk-Stratified Treatment with Zinc Plus Low Dose Hydroxychloroquine and Azithromycin: A Retrospective Case Series Study
518 patient HCQ early treatment study: 79% lower mortality (p=0.12) and 82% lower hospitalization (p=0.001).79% lower mortality and 82% lower hospitalization with early HCQ+AZ+Z. No cardiac side effects. Retrospective 518 patients (141 treated, 377 control).
Jul 2020, Int. J. Antimicrobial Agents, https://www.sciencedirect.com/science/article/pii/S0924857920304258, https://c19p.org/derwand
27. Guérin et al., Azithromycin and Hydroxychloroquine Accelerate Recovery of Outpatients with Mild/Moderate COVID-19
88 patient HCQ early treatment study: 65% faster recovery (p=0.0001).Mean clinical recovery time reduced from 26 days (SOC) to 9 days, p<0.0001 (HCQ+AZ) or 13 days, p<0.0001 (AZ). No cardiac toxicity. Small retrospective study of 88 patients with case control analysis with matched patients.
May 2020, Asian J. Medicine and Health, https://www.journalajmah.com/index.php/AJMAH/article/view/30224, https://c19p.org/guerin
28. Chouhdari et al., The prophylactic effect of hydroxychloroquine on the severity of COVID-19 infection in an asymptomatic population: A randomized clinical trial
1,000 patient HCQ prophylaxis RCT: 80% lower hospitalization (p=0.25) and 43% fewer cases (p=0.005).RCT of 1,000 people showing lower risk of COVID-19 infection with HCQ prophylaxis. There was no significant difference in side effects or adherence, no severe side effects, and blinding was well maintained. There are now PrEP RCTs, showing significant efficacy for COVID-19 cases with .
Jan 2024, Social Determinants of Health, https://journals.sbmu.ac.ir/sdh/article/view/43032, https://c19p.org/chouhdari
3,462 patient HCQ late treatment study: 93% lower mortality (p<0.0001).
Retrospective 3,462 hospitalized COVID-19 patients across 13 states in Nigiera, showing lower mortality with HCQ. Authors note that the improved results compared with many other late stage studies may be related to the dose and experience of the physicians - in other studies beneficial effects may be offset by the side effects of high cumulative doses in late stage patients. Authors also note the worse results with a combination of CQ/HCQ and AZ may be related to the side effects becoming more significant for late stage patients.
May 2023, Nigerian Medical J., https://nigerianmedjournal.org/index.php/nmj/article/view/174, https://c19p.org/yilgwan
30. Obrișcă et al., Characteristics of SARS-CoV-2 Infection in an Actively Monitored Cohort of Patients with Lupus Nephritis
95 patient HCQ prophylaxis study: 87% fewer cases (p=0.01).Prospective analysis of 95 Lupus Nephritis patients in Romania, showing lower risk of COVID-19 with HCQ use.
Sep 2022, Biomedicines, https://www.mdpi.com/2227-9059/10/10/2423, https://c19p.org/obrisca
31. Loucera et al., Real-world evidence with a retrospective cohort of 15,968 COVID-19 hospitalized patients suggests 21 new effective treatments
15,968 patient HCQ prophylaxis study: 69% lower mortality (p=0.0002).Retrospective 15,968 COVID-19 hospitalized patients in Spain, showing lower mortality with existing use of several medications including metformin, HCQ, azithromycin, aspirin, vitamin D, vitamin C, and budesonide. Since only hospitalized patients are included, results do not reflect different probabilities of hospitalization across treatments.
Aug 2022, Virology J., https://virologyj.biomedcentral.com/articles/10.1186/s12985-023-02195-9, https://c19p.org/loucera3h
32. Badyal et al., Hydroxychloroquine for SARS CoV2 Prophylaxis in Healthcare Workers – A Multicentric Cohort Study Assessing Effectiveness and Safety
2,090 patient HCQ prophylaxis study: 60% fewer cases (p<0.0001).Prophylaxis study with 12,089 Indian healthcare workers, showing lower risk of COVID-19 cases with treatment, and increasingly lower risk for longer durations of HCQ prophylaxis. The appendices are not currently available.
Jun 2021, J. the Association of Physicians of India, June 2021, https://www.researchgate.net/publication/357700064_Hydroxychloroquine_for_SARS_CoV2_Prophylaxis_in_Healthcare_Workers_-_A_Multicentric_Cohort_Study_Assessing_Effectiveness_and_Safety, https://c19p.org/badyal
33. Rojas-Serrano et al., Hydroxychloroquine for prophylaxis of COVID-19 in health workers: A randomized clinical trial
127 patient HCQ prophylaxis RCT: 82% fewer symptomatic cases (p=0.12).Early terminated HCQ PrEP RCT with 62 HCQ and 65 placebo patients, showing 82% lower cases with treatment, p = 0.12. If the trial is continued and the same event rate is observed, statistical significance will be reached after adding about 16 patients per arm.
May 2021, PLOS ONE, https://journals.plos.org/plosone/article?id=10.1371/journal.pone.0261980, https://c19p.org/rojasserrano
34. Corradini et al., Clinical factors associated with death in 3044 COVID-19 patients managed in internal medicine wards in Italy: results from the SIMI-COVID-19 study of the Italian Society of Internal Medicine (SIMI)
1,713 patient HCQ late treatment study: 70% lower mortality (p<0.0001).Retrospective 3,044 hospitalized COVID-19 patients in Italy, showing HCQ significantly associated with survival in light, mild, and moderate cases in multivariable analysis, but not in severe cases.
Apr 2021, Internal and Emergency Medicine, https://link.springer.com/article/10.1007/s11739-021-02742-8, https://c19p.org/corradini
35. Cangiano et al., Mortality in an Italian nursing home during COVID-19 pandemic: correlation with gender, age, ADL, vitamin D supplementation, and limitations of the diagnostic tests
98 patient HCQ late treatment study: 73% lower mortality (p=0.03).73% lower mortality with HCQ. Analysis of 98 PCR+ nursing home residents in Italy, mean age 90, showing HCQ mortality RR 0.27, p = 0.03. Subject to confounding by contraindication. The paper provides the p value for regression but not the effect size.
Dec 2020, Aging, https://www.aging-us.com/article/202307/text, https://c19p.org/cangiano
36. Sheshah et al., Prevalence of Diabetes, Management and Outcomes among Covid-19 Adult Patients Admitted in a Specialized Tertiary Hospital in Riyadh, Saudi Arabia
300 patient HCQ late treatment study: 80% lower mortality (p=0.001).Retrospective 300 hospitalized patients in Saudi Arabia showing HCQ adjusted odds ratio aOR 0.12, p < 0.001.
Nov 2020, Diabetes Research and Clinical Practice, https://www.sciencedirect.com/science/article/pii/S0168822720307956, https://c19p.org/sheshah
37. Simova et al., Hydroxychloroquine for prophylaxis and treatment of COVID-19 in health care workers
204 patient HCQ prophylaxis study: 93% fewer cases (p=0.01).100% reduction in cases with HCQ+zinc post-exposure prophylaxis. Brief report for healthcare workers in Bulgaria. 0 cases with treatment vs. 3 for control. 156 treatment patients and 48 control patients. No serious adverse events. This paper reports on both PEP and early treatment, we have separated the two studies.
Nov 2020, New Microbes and New Infections, https://www.sciencedirect.com/science/article/pii/S2052297520301657, https://c19p.org/simovapep
38. Mathai et al., Hydroxychloroquine as pre-exposure prophylaxis against COVID-19 in health-care workers: A single-center experience
604 patient HCQ prophylaxis study: 90% fewer cases (p<0.0001).90% reduction in cases with HCQ pre-exposure prophylaxis. Retrospective 604 healthcare workers.
Nov 2020, J. Marine Medical Society, https://www.marinemedicalsociety.in/preprintarticle.asp?id=300159, https://c19p.org/mathai
39. López et al., Telemedicine follow-ups for COVID-19: experience in a tertiary hospital
72 patient HCQ late treatment study: 64% lower progression (p=0.02).Retrospective 72 pediatric patients showing HCQ associated with a shorter duration of fever (p=0.023), less progression (p=0.016), and fewer return visits to the ER (p=0.017).
Nov 2020, Annals of Pediatrics, https://www.sciencedirect.com/science/article/pii/S1695403320304768, https://c19p.org/lopez2
40. Lauriola et al., Effect of combination therapy of hydroxychloroquine and azithromycin on mortality in COVID-19 patients
360 patient HCQ late treatment study: 74% lower mortality (p=0.001).Retrospective 377 patients, 73% reduction in mortality with HCQ+AZ, adjusted hazard ratio HR 0.27 [0.17-0.41]. Mean age 71.8. No serious adverse events. Subject to incomplete adjustment for confounders.
Sep 2020, Clinical and Translational Science, https://ascpt.onlinelibrary.wiley.com/doi/abs/10.1111/cts.12860, https://c19p.org/lauriola
41. Ferri et al., COVID-19 and rheumatic autoimmune systemic diseases: report of a large Italian patients series
1,641 patient HCQ prophylaxis study: 63% fewer cases (p=0.02).Analysis of 1641 systemic autoimmune disease patients showing csDMARD (HCQ etc.) RR 0.37, p=0.015. csDMARDs include HCQ, CQ, and several other drugs, so the effect of HCQ/CQ alone could be higher. This study also confirms that the risk of COVID-19 for systemic autoimmune disease patients is much higher overall, OR 4.42, p<0.001 (this is the observed real-world risk which takes into account factors such as these patients potentially being more careful to avoid exposure). (results are for "definite + highly suspected" cases and the main result is presented in the paper as the OR for not taking csDMARDs, we have converted this to RR for taking csDMARDs).
Aug 2020, Clinical Rheumatology, https://link.springer.com/article/10.1007/s10067-020-05334-7, https://c19p.org/ferri
36 patient HCQ late treatment study: 88% lower ICU admission (p=0.008).
Retrospective analysis of 36 hospitalized patients showing HCQ/AZ associated with lower ICU admission, p=0.008. Median age 66, no mortality. Confounding by indication, however it was patients with hypoxemic pneumonia that were treated with HCQ/AZ, patients were not treated with HCQ/AZ if they didn't need oxygen therapy.
Aug 2020, J. Global Antimicrobial Resistance, https://www.sciencedirect.com/science/article/pii/S221371652030206X, https://c19p.org/dubernet
43. Kadnur et al., Hydroxychloroquine pre-exposure prophylaxis for COVID-19 among healthcare workers: Initial experience from India
358 patient HCQ prophylaxis study: 62% fewer cases (p=0.01).Prophylaxis study with 334 low-risk healthcare workers in India, showing significantly lower risk of cases with treatment. Symptomatic patients received PCR results, but only some asymptomatic patients did, so there may have been additional asymptomatic cases. There were no severe adverse events.
Jul 2020, J. Family Medicine and Primary Care, https://journals.lww.com/10.4103/jfmpc.jfmpc_1177_21, https://c19p.org/kadnur
44. Zhong et al., COVID-19 in patients with rheumatic disease in Hubei province, China: a multicentre retrospective observational study
43 patient HCQ prophylaxis study: 91% fewer cases (p=0.04).Rheumatic disease patients on HCQ had a lower risk of COVID-19 than those on other disease-modifying anti-rheumatic drugs, OR 0.09 (0.01–0.94), p=0.044 after adjusting for age, sex, smoking, systemic lupus erythematosus, infection in other family members, and comorbidities. 43 patients with rheumatic disease and COVID-19 exposure.
Jul 2020, Lancent Rheumatology, https://www.thelancet.com/journals/lanrhe/article/PIIS2665-9913(20)30227-7/fulltext, https://c19p.org/zhong
45. Rogado et al., Covid-19 and lung cancer: A greater fatality rate?
17 patient HCQ late treatment study: 92% lower mortality (p=0.02).Retrospective 17 hospitalized lung cancer patients showing lower mortality with HCQ+AZ treatment.
May 2020, Lung Cancer, https://www.lungcancerjournal.info/article/S0169-5002(20)30468-2/fulltext, https://c19p.org/rogado
46. Chatterjee et al., Healthcare workers & SARS-CoV-2 infection in India: A case-control investigation in the time of COVID-19
455 patient HCQ prophylaxis study: 67% fewer cases (p=0.001).4+ doses of HCQ associated with a significant decline in the odds of getting infected, dose-response relationship exists.
May 2020, Indian J. Medical Research, https://www.ijmr.org.in/article.asp?issn=0971-5916;year=2020;volume=151;issue=5;spage=459;epage=467;aulast=Chatterjee, https://c19p.org/chatterjee
47. Huang et al., Preliminary evidence from a multicenter prospective observational study of the safety and efficacy of chloroquine for the treatment of COVID-19
373 patient HCQ late treatment study: 67% faster viral clearance (p=0.0001).197 CQ patients, 176 control. Mean time to undetectable viral RNA and duration of fever significantly reduced. No serious adverse events.
May 2020, National Science Review, https://academic.oup.com/nsr/advance-article/doi/10.1093/nsr/nwaa113/5848167, https://c19p.org/huangnsr
48. Yu et al., Low Dose of Hydroxychloroquine Reduces Fatality of Critically Ill Patients With COVID-19
550 patient HCQ late treatment study: 60% lower mortality (p=0.002).Retrospective, 550 critically ill patients. 19% fatality for HCQ versus 47% for non-HCQ, RR 0.395, p=0.002. The levels of inflammatory cytokine IL-6 were significantly reduced from 22.2 pg/mL to 5.2 pg/mL (p<0.05) at the end of the treatment in the HCQ group but there was no change in the control group.
May 2020, Science China Life Sciences, 2020 May 15, 1-7, https://link.springer.com/article/10.1007%2Fs11427-020-1732-2, https://c19p.org/yu
49. Yadav et al., Sero-survey for health-care workers provides corroborative evidence for the effectiveness of Hydroxychloroquine prophylaxis against COVID-19 infection
500 patient HCQ prophylaxis study: 82% lower hospitalization (p=0.01) and 42% fewer cases (p=0.05).ICMR seroprevalence survey of 500 healthcare workers in India, 279 taking HCQ prophylaxis, showing a significantly lower risk with treatment, and lower severity.
Sep 2020, ResearchGate, https://www.researchgate.net/publication/344221734_Sero-survey_for_health-care_workers_provides_corroborative_evidence_for_the_effectiveness_of_Hydroxychloroquine_prophylaxis_against_COVID-19_infection, https://c19p.org/yadav3
50. Mokhtari et al., Clinical outcomes of patients with mild COVID-19 following treatment with hydroxychloroquine in an outpatient setting
28,759 patient HCQ early treatment study: 70% lower mortality (p<0.0001) and 35% lower hospitalization (p<0.0001).Retrospective 28,759 adult outpatients with mild COVID-19 in Iran, 7,295 treated with HCQ, showing significantly lower hospitalization and mortality with treatment.
Apr 2021, Int. Immunopharmacology, https://www.sciencedirect.com/science/article/pii/S1567576921002721, https://c19p.org/mokhtari
51. AlQahtani et al., Randomized controlled trial of favipiravir, hydroxychloroquine, and standard care in patients with mild/moderate COVID-19 disease
103 patient HCQ late treatment RCT: 4% improved recovery (p=0.94) and 47% improved viral clearance (p=0.13).RCT with 54 favipiravir, 51 HCQ, and 52 SOC hospitalized patients in Bahrain, showing no significant differences. Viral clearance improved with both treatments, but did not reach statistical significance with the small sample size.
Mar 2022, Scientific Reports, https://www.nature.com/articles/s41598-022-08794-w, https://c19p.org/alqahtani2
52. Ip et al., Hydroxychloroquine in the treatment of outpatients with mildly symptomatic COVID-19: A multi-center observational study
1,067 patient HCQ early treatment study: 55% lower mortality (p=0.43) and 37% lower hospitalization (p=0.04).Retrospective 1,274 outpatients, 47% reduction in hospitalization with HCQ with propensity matching, HCQ OR 0.53 [0.29-0.95]. Sensitivity analyses revealed similar associations. Adverse events were not increased (2% QTc prolongation events, 0% arrhythmias).
Aug 2020, BMC Infectious Diseases, https://bmcinfectdis.biomedcentral.com/articles/10.1186/s12879-021-05773-w, https://c19p.org/ip
296 patient HCQ early treatment study: 81% lower mortality (p=0.21), 95% lower ventilation (p=0.0008), and 98% lower hospitalization (p<0.0001).
Comparison of HCQ, nitazoxanide, and ivermectin showing similar effectiveness for overall clinical outcomes in COVID-19 when used before seven days of symptoms, and overwhelmingly superior compared to the untreated COVID-19 population, even for those outcomes not influenced by placebo effect, at least when combined with azithromycin, and vitamin C, D and zinc in the majority of the cases. 585 patients with mean treatment delay 2.9 days. There was no hospitalization, mechanical ventilation, or mortality with treatment. Control group 1 was a retrospectively obtained group of untreated patients of the same population.
Nov 2020, New Microbes and New Infections, https://www.sciencedirect.com/science/article/pii/S2052297521000792, https://c19p.org/cadegiani
54. Dhibar et al., The ‘myth of Hydroxychloroquine (HCQ) as post-exposure prophylaxis (PEP) for the prevention of COVID-19’ is far from reality
1,168 patient HCQ prophylaxis RCT: 27% fewer symptomatic cases (p=0.32) and 21% fewer cases (p=0.21).Low dose low-risk patient HCQ PEP RCT, showing lower symptomatic cases with treatment, without statistical significance. There were no moderate or severe cases. HCQ 800mg on day one followed by 400mg once weekly for 3 weeks.
Jan 2023, Scientific Reports, https://www.nature.com/articles/s41598-022-26053-w, https://c19p.org/dhibar2
55. Ly et al., Pattern of SARS-CoV-2 infection among dependant elderly residents living in retirement homes in Marseille, France, March-June 2020
226 patient HCQ early treatment study: 56% lower mortality (p=0.02).Retrospective analysis of retirement homes, HCQ+AZ >= 3 days mortality OR 0.37, p=0.02. 1,690 elderly residents (mean age 83), 226 infected residents, 116 treated with HCQ+AZ >= 3 days. Detection via mass screening also showed significant improvements (16.9% vs. 40.6%, OR 0.20, p=0.001), suggesting that earlier detection and treatment is more successful.
Aug 2020, Int. J. Antimicrobial Agents, https://www.sciencedirect.com/science/article/abs/pii/S0924857920304301, https://c19p.org/ly
56. Skipper et al., Hydroxychloroquine in Nonhospitalized Adults With Early COVID-19: A Randomized Trial
465 patient HCQ early treatment RCT: 37% lower combined mortality/hospitalization (p=0.58), 49% lower hospitalization (p=0.38), and 20% improved recovery (p=0.21).Update: we have not received details for treatment delay. An author reports that treatment initiation time was not recorded: [osf.io]. Conflicting estimates are provided in a comment of the article and independent analysis, with reports indicating missing data in the dataset. Also see [medrxiv.org] (companion PEP trial), and Pullen et al. [ncbi.nlm.nih.gov], which shows shipping delay for these trials of 19 - 68 hours. Only one third of participants completed enrollment weekdays between 8:00am and 4:00pm, with 44% outside of these hours during the week, and 22% during the weekend. With enrollment up to 4 days after symptom onset, this implies delivery 19 - 164 hours after onset (19 hours would require instantaneous enrollment). ~70 to 140 hour (inc. shipping) delayed outpatient treatment with HCQ showing lower hospitalization/death and faster recovery, but not reaching statistical significance. There was one hospitalized control death and one non-hospitalized HCQ death. It is unclear..
Jul 2020, Annals of Internal Medicine, https://www.acpjournals.org/doi/10.7326/M20-4207, https://c19p.org/skipper
57. Smith et al., Evaluating the Efficacy of Hydroxychloroquine and Azithromycin to Prevent Hospitalization or Death in Persons With COVID-19
16 patient HCQ early treatment RCT: 64% lower hospitalization (p=1) and 10% slower recovery.Early terminated NIAID RCT for HCQ. Patients >60 were only in the HCQ arm. 57% of patients were high risk in the HCQ arm vs. 22% for control. Treatment started up to 20 days after symptoms.
Jul 2020, NCT04358068, https://clinicaltrials.gov/study/NCT04358068, https://c19p.org/smith2
97 patient HCQ late treatment study: 51% shorter hospitalization (p=0.01) and 56% faster viral clearance (p=0.005).
Retrospective of 97 moderate cases. Time to viral clearance significantly shorter for HCQ+antibiotic. Preprint withdrawn pending peer review.
May 2020, medRxiv, https://www.medrxiv.org/content/10.1101/2020.05.13.20094193v1?versioned=true, https://c19p.org/kim
59. Núñez-Gil et al., Hydroxychloroquine and Mortality in SARS-Cov-2 Infection; The HOPE- Covid-19 Registry.
6,217 patient HCQ late treatment PSM study: 53% lower mortality (p<0.0001).PSM retrospective 6,217 hospitalized patients in Spain, showing lower mortality with HCQ. The higher efficacy reported with obesity is consistent with the greater efficacy predicted for higher cholesterol [Yuan].
Sep 2022, Anti-Infective Agents, https://www.eurekaselect.com/204783/article, https://c19p.org/nunezgil2
60. Ugarte-Gil et al., Characteristics associated with poor COVID-19 outcomes in individuals with systemic lupus erythematosus: data from the COVID-19 Global Rheumatology Alliance
895 patient HCQ prophylaxis study: 44% lower severe cases (p=0.007).Retrospective 1,606 SLE patients showing lower risk of severe COVID-19 outcomes with HCQ/CQ use.
Feb 2022, Annals of the Rheumatic Diseases, https://ard.bmj.com/content/early/2022/02/15/annrheumdis-2021-221636.long, https://c19p.org/ugartegil
61. Lora-Tamayo et al., Early Lopinavir/ritonavir does not reduce mortality in COVID-19 patients: results of a large multicenter study
8,553 patient HCQ late treatment study: 50% lower mortality (p<0.0001).Lopinavir/ritonavir retrospective study also showing univariate results for HCQ, with significantly lower mortality.
Feb 2021, J. Infection, https://www.sciencedirect.com/science/article/pii/S0163445321000773, https://c19p.org/loratamayo
62. Di Castelnuovo et al., Disentangling the Association of Hydroxychloroquine Treatment with Mortality in Covid-19 Hospitalized Patients through Hierarchical Clustering
4,270 patient HCQ late treatment study: 40% lower mortality (p<0.0001).Retrospective 4,396 hospitalized patients in Italy showing significantly lower mortality with HCQ treatment, and identifying greater efficacy for a subgroup of patients in clustering analysis.
Jan 2021, J. Healthcare Engineering, https://www.hindawi.com/journals/jhe/2021/5556207/, https://c19p.org/dicastelnuovo2
63. Strangfeld et al., Factors associated with COVID-19-related death in people with rheumatic diseases: results from the COVID-19 Global Rheumatology Alliance physician-reported registry
1,165 patient HCQ prophylaxis study: 48% lower mortality (p<0.0001).Retrospective 3,729 rheumatic disease patients showing lower risk of mortality with HCQ/CQ use (HCQ/CQ vs. no DMARD therapy).
Jan 2021, Annals of the Rheumatic Diseases, https://ard.bmj.com/content/80/7/930, https://c19p.org/strangfeld
64. Signes-Costa et al., Prevalence and 30-day mortality in hospitalized patients with COVID-19 and prior lung diseases
5,847 patient HCQ late treatment study: 47% lower mortality (p=0.0005).47% lower mortality with HCQ/CQ. Retrospective 1,271 patients with lung disease in Canada, China, Cuba, Ecuador, Germany, Italy and Spain, 83% treated with HCQ/CQ. Multivariable Cox regression HCQ/CQ mortality hazard ratio HR 0.53, p < 0.001.
Dec 2020, Archivos de Bronconeumología, https://www.sciencedirect.com/science/article/pii/S0300289620305354, https://c19p.org/signescosta
65. Polat et al., Hydroxychloroquine Use on Healthcare Workers Exposed to COVID-19 - A Pandemic Hospital Experience
208 patient HCQ prophylaxis study: 57% fewer cases (p=0.03).Small prophylaxis study of 208 healthcare workers in Turkey, 138 with high risk exposure received HCQ, while 70 with low and medium risk exposure did not. COVID-19 cases were lower in the treatment group, relative risk RR 0.43, p = 0.026. Since the control group had lower risk, the actual benefit may be larger.
Sep 2020, Medical J. Bakirkoy, 280-6, https://cms.galenos.com.tr/Uploads/Article_47752/BTD-16-280-En.pdf, https://c19p.org/polat
66. Ayerbe et al., The association of treatment with hydroxychloroquine and hospital mortality in COVID-19 patients
2,075 patient HCQ late treatment study: 52% lower mortality (p=0.001).2075 hospital patients in Spain showing HCQ reduces mortality 52%, odds ratio OR 0.39, p<0.001, after adjustment for age, gender, temperature > 37 °C, and saturation of oxygen < 90% treatment with azithromycin, steroids, heparin, tocilizumab, a combination of lopinavir with ritonavir, and oseltamivir, and date of admission (model 4).
Sep 2020, Internal and Emergency Medicine, https://link.springer.com/article/10.1007/s11739-020-02505-x, https://c19p.org/ayerbe
67. Pinato et al., Clinical portrait of the SARS-CoV-2 epidemic in European cancer patients
890 patient HCQ late treatment study: 59% lower mortality (p=0.0001).Retrospective 890 cancer patients with COVID-19, adjusted mortality HR for HCQ/CQ 0.41, p<0.0001. Confirmed SARS-CoV-2 infection was required, which may help focus on more severe cases. Analysis with Cox proportional hazard model. Potential unmeasured confounders.
Aug 2020, Cancer Discovery, https://cancerdiscovery.aacrjournals.org/content/early/2020/08/18/2159-8290.CD-20-0773, https://c19p.org/pinato
68. Davido et al., Impact of medical care including anti-infective agents use on the prognosis of COVID-19 hospitalized patients over time
132 patient HCQ late treatment study: 55% lower combined intubation/hospitalization (p=0.04).Retrospective of 132 hospitalized patients. HCQ+AZ(52)/AZ(28) significantly reduced death/ICU, HR=0.45, p=0.04. Adjusted for Charlson Comorbidity Index (including age), obesity, O2, lymphocyte count, and treatments. Mean delay from admission to treatment 0.7 days.
Aug 2020, Int. J. Antimicrobial Agents, 2020, https://www.sciencedirect.com/science/article/pii/S0924857920303125, https://c19p.org/davido
69. Arshad et al., Treatment with Hydroxychloroquine, Azithromycin, and Combination in Patients Hospitalized with COVID-19
2,541 patient HCQ late treatment study: 51% lower mortality (p=0.009).HCQ decreases mortality from 26.4% to 13.5% (HCQ) or 20.1% (HCQ+AZ). Propensity matched HCQ HR 0.487, p=0.009. Michigan 2,541 patients retrospective. Before propensity matching the HCQ group average age is 5 years younger and the percentage of male patients is 4% higher which is likely to favor the treatment and the control respectively in the before-propensity matching results. Some reported limtiations of this study are inaccurate [ijidonline.com]. Corticosteroids were controlled for in the multivariate and propensity analyses as were age and comorbidities including cardiac disease and severity of illness. Age was an independent risk factor associated with mortality. HCQ was independently associated with decreased mortality, distinct from the steroid effect. 91% of all patients began treatment within two days of admission. HCQ was used throughout the study period, limiting time bias. Patients assigned to HCQ group had moderate and severe illness at presentation, which would favor..
Jun 2020, Int. J. Infectious Diseases, https://www.ijidonline.com/article/S1201-9712(20)30534-8/fulltext, https://c19p.org/arshad
70. Mikami et al., Risk Factors for Mortality in Patients with COVID-19 in New York City
6,000 patient HCQ late treatment study: 47% lower mortality (p<0.0001).HCQ decreases mortality, HR 0.53 (CI 0.41–0.67). IPTW adjustment does not significantly change HR 0.53 (0.41-0.68). Retrospective 6,000 patients in New York City.
Jun 2020, J. Gen. Intern. Med., https://link.springer.com/article/10.1007/s11606-020-05983-z, https://c19p.org/mikami
71. Ferreira et al., Chronic treatment with hydroxychloroquine and SARS-CoV-2 infection
26,815 patient HCQ prophylaxis study: 47% fewer cases (p<0.0001).Chronic treatment with HCQ provides protection against COVID, odds ratio 0.51 (0.37-0.70). The actual benefit is likely to be larger becasue research shows that the risk of COVID-19 for systemic autoimmune disease patients is much higher overall. Ferri et al. show OR 4.42, p<0.001 [Ferri], which is the observed real-world risk, taking into account factors such as these patients potentially being more careful to avoid exposure.
Jun 2020, J. Medical Virology, https://onlinelibrary.wiley.com/doi/full/10.1002/jmv.26286, https://c19p.org/ferreira
72. Lagier et al., Outcomes of 3,737 COVID-19 patients treated with hydroxychloroquine/azithromycin and other regimens in Marseille, France: A retrospective analysis
3,737 patient HCQ late treatment study: 59% lower mortality (p=0.05).Early treatment leads to significantly better clinical outcome and faster viral load reduction. Matched sample mortality HR 0.41 p-value 0.048. Retrospective 3,737 patients. This study includes both outpatients and hospitalized patients.
Jun 2020, Travel Medicine and Infectious Disease, https://www.sciencedirect.com/science/article/pii/S1477893920302817, https://c19p.org/lagier
73. Sánchez-Álvarez et al., Status of SARS-CoV-2 infection in patients on renal replacement therapy. Report of the COVID-19 Registry of the Spanish Society of Nephrology (SEN)
375 patient HCQ late treatment study: 46% lower mortality (p=0.005).Analysis of 868 patients on renal replacement therapy. Statistically significant reduction in mortality with HCQ for patients on dialysis (OR 0.47, p=0.005). No statistically significant change was found for transplant patients (the result is not given but likely the sample size is too small - the number of transplant patients was half the number of dialysis patients).
Apr 2020, Nefrología, https://www.sciencedirect.com/science/article/pii/S201325142030050X, https://c19p.org/sanchezalvarez
74. Esper et al., Empirical treatment with hydroxychloroquine and azithromycin for suspected cases of COVID-19 followed-up by telemedicine
636 patient HCQ early treatment study: 64% lower hospitalization (p=0.02).636 patients. HCQ+AZ reduced hospitalization 79% when used within 7 days (65% overall). Non-randomized.
Apr 2020, Prevent Senior Institute, São Paulo, Brazil, https://pgibertie.com/wp-content/uploads/2020/04/2020.04.15-journal-manuscript-final.pdf, https://c19p.org/esper
75. Agusti et al., Efficacy and safety of hydroxychloroquine in healthcare professionals with mild SARS-CoV-2 infection: prospective, non-randomized trial
142 patient HCQ early treatment study: 68% lower progression (p=0.21) and 32% faster viral clearance.Small trial of low dose HCQ for healthcare workers with mild SARS-CoV-2 showing 68% lower progression to pneumonia, p = 0.21, and faster, but not statistically significant viral clearance. There were no ICU admissions or deaths. Prospective non-randomized study. The figures and supplementary data are not currently available in the pre-proof edition.
Dec 2020, Enfermedades Infecciosas y Microbiología Clínica, https://www.sciencedirect.com/science/article/abs/pii/S0213005X20304134, https://c19p.org/agusti
76. Heberto et al., Implications of myocardial injury in Mexican hospitalized patients with coronavirus disease 2019 (COVID-19)
254 patient HCQ late treatment study: 54% lower mortality (p=0.04) and 65% lower ventilation (p=0.008).Observational prospective 254 hospitalized patients, HCQ+AZ mortality odds ratio OR 0.36, p = 0.04. Ventilation OR 0.20, p = 0.008.
Sep 2020, IJC Heart & Vasculature, https://www.sciencedirect.com/science/article/pii/S2352906720303365, https://c19p.org/heberto
77. Gautret et al., Hydroxychloroquine and azithromycin as a treatment of COVID-19: results of an open-label non-randomized clinical trial
36 patient HCQ early treatment study: 66% improved viral clearance (p=0.001).HCQ was significantly associated with reduction / elimination of viral load, which was enhanced with AZ. Updated 8/13: responses to this paper have raised methodological issues [sciencedirect.com, sciencedirect.com, sciencedirect.com]. Despite the limitations, this early observational study was a milestone in the discovery process, including detailed daily evolution of PCR positivity. This study should be viewed in the context of the series of studies from this group. An update to this paper, including originally excluded patients, confirms the effectiveness of HCQ+AZ on viral clearance and early discharge [sciencedirect.com]. Also see [sciencedirect.com] and the response from the authors [sciencedirect.com].
Mar 2020, Int. J. Antimicrobial Agents, https://www.sciencedirect.com/science/article/abs/pii/S0924857920300996, https://c19p.org/gautretjaa
78. Ouedraogo et al., Factors associated with the occurrence of acute respiratory distress and death in patients with COVID-19 in Burkina Faso
456 patient HCQ late treatment study: 33% lower mortality (p=0.38) and 68% lower severe cases (p=0.001).Retrospective 456 patients in Burkina Faso showing lower risk of ARDS (p=0.001) and mortality (p=0.38) with HCQ.
Feb 2021, Revue des Maladies Respiratoires, https://www.sciencedirect.com/science/article/pii/S0761842521000383, https://c19p.org/ouedraogo
79. Dhibar et al., Post Exposure Prophylaxis with Hydroxychloroquine (HCQ) for the Prevention of COVID-19, a Myth or a Reality? The PEP-CQ Study
317 patient HCQ prophylaxis study: 44% fewer symptomatic cases (p=0.21) and 50% fewer cases (p=0.04).Low dose prospective PEP study with 132 HCQ patients and 185 control patients, showing significantly lower COVID-19 cases with treatment. There were no serious adverse events. HCQ 800mg on day one followed by 400mg once weekly for 3 weeks.
Nov 2020, Int. J. Antimicrobial Agents, https://www.sciencedirect.com/science/article/pii/S0924857920304350, https://c19p.org/dhibar
80. Atipornwanich et al., Various Combinations of Favipiravir, Lopinavir-Ritonavir, Darunavir-Ritonavir, High-Dose Oseltamivir, and Hydroxychloroquine for the Treatment of COVID-19: A Randomized Controlled Trial (FIGHT-COVID-19 Study)
200 patient HCQ late treatment RCT: 56% lower mortality (p=0.07), 54% lower progression (p=0.02), and 7% faster viral clearance (p=0.51).RCT 320 patients in Thailand, showing significantly lower progression with HCQ for moderate/severe patients, and faster viral clearance with mild patients (statistically significant for 800mg). There are two sets of results - for moderate/severe patients, and for mild patients. There was no mortality for mild patients. NCT04303299.
Oct 2021, SSRN Electronic J., https://papers.ssrn.com/sol3/papers.cfm?abstract_id=3936499, https://c19p.org/atipornwanich
81. Goenka et al., Seroprevalence of COVID-19 Amongst Health Care Workers in a Tertiary Care Hospital of a Metropolitan City from India
962 patient HCQ prophylaxis study: 87% lower IgG positivity (p=0.03).Study of SARS-CoV-2-IgG antibodies in 1122 health care workers in India finding 87% lower positives for adequate HCQ prophylaxis, 1.3% HCQ versus 12.3% for no HCQ prophylaxis. Adequate prophylaxis is defined as 400mg 1/wk for >6 weeks.
Oct 2020, SSRN, https://papers.ssrn.com/sol3/papers.cfm?abstract_id=3689618, https://c19p.org/goenka
82. Lyngbakken et al., A pragmatic randomized controlled trial reports lack of efficacy of hydroxychloroquine on coronavirus disease 2019 viral kinetics
53 patient HCQ late treatment RCT: 4% lower mortality (p=1) and 71% improved viral reduction rate (p=0.51).Small RCT of nasopharyngeal viral load not showing significant differences. The rate of reduction for HCQ was 0.24 [0.03-0.46] RNA copies/mL/24h, and 0.14 [-0.10-0.37] for the control group (71% faster with HCQ but not statistically significant with the small sample size of 27 HCQ and 26 control patients). Analysis only over 96 hours. NCT04316377.
Jul 2020, Nature Communications, https://www.nature.com/articles/s41467-020-19056-6, https://c19p.org/lyngbakken
83. Bhattacharya et al., Pre exposure Hydroxychloroquine use is associated with reduced COVID19 risk in healthcare workers
106 patient HCQ prophylaxis study: 81% fewer cases (p=0.001).HCQ reduced cases from 38% to 7%. 106 people. No serious adverse effects.
Jun 2020, medRxiv, https://www.medrxiv.org/content/10.1101/2020.06.09.20116806v1, https://c19p.org/bhattacharya
84. Zhong Nanshan (钟南山) et al., Efficacy and safety of chloroquine for treatment of COVID-19. An open-label, multi-center, non-randomized trial
197 patient HCQ late treatment study: 80% improved viral clearance (p=0.0001).197 patients. CQ effective. Day 10 viral RNA negative 91.4% HCQ versus 57.4% control. Median time to negative test 3 days versus 9 days for control.
Mar 2020, Zhong Nanshan, https://twitter.com/JamesTodaroMD/status/1243260720944480265, https://c19p.org/zhong2
85. Isnardi et al., Sociodemographic and clinical factors associated with poor COVID-19 outcomes in patients with rheumatic diseases: data from the SAR-COVID Registry
2,066 patient HCQ prophylaxis study: 34% lower mortality (p=0.23), 48% lower severe cases (p=0.02), and 17% lower hospitalization (p=0.09).Retrospective 1,915 rheumatic disease patients with COVID-19 in Argentina, showing lower mortality, severe oxygen requirement, and hospitalization with CQ/HCQ (antimalarial) use in unadjusted results, statistically significant only for severe oxygen requirement.
Oct 2022, Clinical Rheumatology, https://link.springer.com/10.1007/s10067-022-06393-8, https://c19p.org/isnardi
86. Sobngwi et al., Doxycycline vs Hydroxychloroquine + Azithromycin in the Management of COVID-19 Patients: An Open-Label Randomized Clinical Trial in Sub-Saharan Africa (DOXYCOV)
187 patient HCQ early treatment RCT: 52% improved recovery (p=0.44) and 3% improved viral clearance (p=0.88).RCT 194 mild/asymptomatic low-risk patients in Cameroon, 97 treated with HCQ+AZ and 97 treated with doxycycline, showing 2.1% symptomatic patients at day 10 with HCQ+AZ, versus 4.3% with doxycycline, without statistical significance. There were only 6 patients with symptoms at day 10. There was no mortality or hospitalization, and no major adverse events.
Jul 2021, Cureus, https://www.cureus.com/articles/179159-doxycycline-vs-hydroxychloroquine--azithromycin-in-the-management-of-covid-19-patients-an-open-label-randomized-clinical-trial-in-sub-saharan-africa-doxycov, https://c19p.org/sobngwi
87. Sivapalan et al., Azithromycin and hydroxychloroquine in hospitalised patients with confirmed COVID-19–a randomised double-blinded placebo-controlled trial
117 patient HCQ late treatment RCT: 92% lower mortality (p=0.32), 22% higher ICU admission (p=1), and 8% lower hospital discharge (p=0.36).Early terminated late stage (8 days from onset, 59% on oxygen) RCT not showing statistically significant differences. NNF20SA0062834.
Jun 2021, European Respiratory J., https://erj.ersjournals.com/content/early/2021/05/28/13993003.00752-2021.article-info, https://c19p.org/sivapalan
88. Omrani et al., Randomized double-blinded placebo-controlled trial of hydroxychloroquine with or without azithromycin for virologic cure of non-severe Covid-19
456 patient HCQ early treatment RCT: 12% lower hospitalization (p=1), 26% improved recovery (p=0.58), and 10% worse viral clearance (p=0.13).Low risk patient RCT for HCQ+AZ and HCQ vs. control, not showing any significant differences. Authors note that the results are not applicable to higher risk patients, that positive PCR may simply reflect detection of inactive (non-infectious) viral remnants, that an alternative dosage regimen may be more effective, and that medication adherence was unknown. HCQ dosing was 600mg/day for 1 week, therapeutic levels may not be reached for several days. There were no deaths or serious adverse events. Viral load was already very high at baseline.
Nov 2020, eClinicalMedicine, https://www.sciencedirect.com/science/article/pii/S2589537020303898, https://c19p.org/omrani
89. Korkmaz et al., The effect of Hydroxychloroquine use due to rheumatic disease on the risk of Covid-19 infection and its course
694 patient HCQ prophylaxis study: 82% lower mortality (p=0.19) and 94% fewer cases (p<0.0001).Retrospective 683 patients in a rheumatology department, 384 chronic HCQ users and 299 control patients, showing no mortality for HCQ users vs. 2 deaths in the control group, and significantly fewer cases for HCQ users.
May 2021, Authorea, https://www.authorea.com/doi/full/10.22541/au.162257516.68665404, https://c19p.org/korkmaz
90. Finkelstein et al., The Efficacy of Long-Term Hydroxychloroquine Use in the Prevention of COVID-19: A Retrospective Cohort Study
110,038 patient HCQ prophylaxis PSM study: 21% fewer cases (p=0.0007).PSM retrospective SLE/RA patients in the USA, showing lower COVID-19 cases with HCQ prophylaxis.
Jun 2023, Studies in Health Technology and Informatics, https://ebooks.iospress.nl/doi/10.3233/SHTI230489, https://c19p.org/finkelstein
91. AlQadheeb et al., Impact of common comorbidities on antimicrobial consumption and mortality amongst critically ill COVID-19 patients: A retrospective two center study in Saudi Arabia
848 patient HCQ ICU study: 35% lower mortality (p=0.0001).Retrospective 848 ICU patients in Saudi Arabia, showing lower mortality with HCQ in unadjusted results.
May 2023, Clinical Infection in Practice, https://www.sciencedirect.com/science/article/pii/S2590170223000122, https://c19p.org/alqadheeb
92. Bubenek-Turconi et al., Clinical characteristics and factors associated with ICU mortality during the first year of the SARS-Cov-2 pandemic in Romania
HCQ ICU study: 22% lower mortality (p=0.01).Prospective study of 9,058 COVID-19 ICU patients in Romania, showing lower mortality with HCQ treatment.
Nov 2022, European J. Anaesthesiology, https://journals.lww.com/10.1097/EJA.0000000000001776, https://c19p.org/bubenekturconi
93. Go et al., Hydroxychloroquine, azithromycin and methylprednisolone and in hospital survival in severe COVID-19 pneumonia
HCQ late treatment study: 55% lower mortality (p=0.03).Retrospective 759 hospitalized patients in the USA, showing lower mortality with combined HCQ+AZ+methylprednisolone treatment compared to methylprednisolone monotherapy.
Sep 2022, Frontiers in Pharmacology, https://www.frontiersin.org/articles/10.3389/fphar.2022.935370/full, https://c19p.org/go2
94. Bowen et al., Reduction in risk of death among patients admitted with COVID-19 between first and second epidemic waves in New York City
4,631 patient HCQ late treatment study: 20% lower mortality (p=0.007).Retrospective 4,631 hospitalized patients in New York, showing higher mortality with remdesivir, and lower mortality with HCQ. Authors suggest that increased mortality during the first epidemic wave was partly due to strain on hospital resources.
Aug 2022, Open Forum Infectious Diseases, https://academic.oup.com/ofid/advance-article/doi/10.1093/ofid/ofac436/6675651, https://c19p.org/bowen
95. Yadav et al., Hydroxychloroquine/chloroquine prophylaxis among health-care workers: Was it really preventive? – Evidence from a multicentric cross-sectional study
2,224 patient HCQ prophylaxis study: 20% lower seropositivity (p=0.1).Retrospective 2,224 healthcare workers in India, showing lower risk of seropositivity with HCQ prophylaxis, without statistical significance.
Jul 2022, Indian J. Community Medicine, http://www.ijcm.org.in/text.asp?2022/47/2/202/350357, https://c19p.org/yadav4
96. Ebongue et al., Factors predicting in-hospital all-cause mortality in COVID 19 patients at the Laquintinie Hospital Douala, Cameroon
580 patient HCQ late treatment study: 43% lower mortality (p=0.04).Retrospective 580 hospitalized COVID+ patients in Cameroon, showing lower mortality with HCQ+AZ treatment.
Mar 2022, Travel Medicine and Infectious Disease, https://www.sciencedirect.com/science/article/pii/S1477893922000382, https://c19p.org/ebongue
97. Lavilla Olleros et al., Use of glucocorticoids megadoses in SARS-CoV-2 infection in a spanish registry: SEMI-COVID-19
14,921 patient HCQ late treatment study: 36% lower mortality (p<0.0001).Retrospective 14,921 hospitalized patients in Spain, showing lower mortality with HCQ treatment.
Jan 2022, PLOS ONE, https://journals.plos.org/plosone/article?id=10.1371/journal.pone.0261711, https://c19p.org/lavillaolleros
98. McKinnon et al., Safety and Tolerability of Hydroxychloroquine in healthcare workers and first responders for the prevention of COVID-19: WHIP COVID-19 Study
543 patient HCQ prophylaxis RCT: 2% fewer symptomatic cases (p=1) and 51% fewer cases (p=0.6).HCQ prophylaxis RCT with 201 weekly HCQ patients, 197 daily HCQ patients, and 200 control patients, concluding the prophylaxis is safe. There were no grade 3 or 4 AEs, SAEs, ER visits, or hospitalizations. There was only 4 confirmed cases, 2 in the placebo arm and one in each HCQ arm. 60% of patients had exposure at baseline. HCQ 400mg weekly or HCQ 200mg daily after a loading dose of 400mg on day 1.
Dec 2021, Int. J. Infectious Diseases, https://www.sciencedirect.com/science/article/pii/S1201971221012431, https://c19p.org/mckinnon
99. Panda et al., Antiviral Combination Clinically Better Than Standard Therapy in Severe but Not in Non-Severe COVID-19
41 patient HCQ late treatment RCT: 48% lower mortality (p=0.45).RCT 111 patients in India in 5 groups: severe patients: a) standard treatment, b) hydroxychloroquine + ribavirin + standard treatment, or c) lopinavir + ritonavir + ribavirin + standard treatment, and non-severe: a) standard treatment or b) hydroxychloroquine + ribavirin. Non-severe patients were transferred to the severe group on progression.
Sep 2021, Clinical Pharmacology: Advances and Applications, https://www.dovepress.com/antiviral-combination-clinically-better-than-standard-therapy-in-sever-peer-reviewed-fulltext-article-CPAA, https://c19p.org/panda2
100. Naggie et al., Hydroxychloroquine for pre-exposure prophylaxis of COVID-19 in health care workers: A randomized, multicenter, placebo-controlled trial (HERO-HCQ)
1,359 patient HCQ prophylaxis RCT: 24% fewer symptomatic cases (p=0.18).HCQ prophylaxis RCT reporting statistically significant lower cases when pooling results with the COVID PREP RCT, OR 0.74 [0.55-1.0] p = 0.046. There were no significant safety issues. The trials were both terminated early resulting in a loss of power, however the combination shows statistically significant efficacy of HCQ. Note that this result has been censored in the journal version, see [medrxiv.org]. The journal paper still shows the COVID PREP paper in the reference list, but the analysis and discussion has been deleted. The journal version falsely states: "The prophylactic use of HCQ by HCW was safe but not effective", whereas the paper actually estimates OR 0.75, which becomes statistically significant OR 0.74 when pooled with COVID PREP. The preprint contains a different version: "...but did not produce a clinically useful treatment". It's unclear why ~25% fewer cases would not be useful. They also state "This is one of several negative studies"..
Aug 2021, Int. J. Infectious Diseases, https://www.sciencedirect.com/science/article/pii/S120197122300019X, https://c19p.org/naggie
101. Taieb et al., Hydroxychloroquine and Azithromycin Treatment of Hospitalized Patients Infected with SARS-CoV-2 in Senegal from March to October 2020
926 patient HCQ late treatment study: 39% higher hospital discharge (p=0.02).Retrospective 926 patients in Senegal, 674 treated with HCQ+AZ, showing significantly higher hospital discharge at day 15 with treatment.
Jun 2021, J. Clinical Medicine, https://www.mdpi.com/2077-0383/10/13/2954, https://c19p.org/taieb
102. Lagier et al., Outcomes of 2,111 COVID-19 hospitalised patients treated with 2 hydroxychloroquine/azithromycin and other regimens in Marseille, France: a 3 monocentric retrospective analysis
2,111 patient HCQ late treatment study: 32% lower mortality (p=0.004).Retrospective 2,011 hospitalized patients in France, median age 67, showing lower mortality with HCQ+AZ, and further benefit with the addition of zinc.
Jun 2021, Therapeutics and Clinical Risk Management, https://www.dovepress.com/outcomes-of-2111-covid-19-hospitalized-patients-treated-with-hydroxych-peer-reviewed-fulltext-article-TCRM, https://c19p.org/lagier2
103. De Rosa et al., Risk Factors for Mortality in COVID-19 Hospitalized Patients in Piedmont, Italy: Results from the Multicenter, Regional, CORACLE Registry
1,538 patient HCQ late treatment study: 35% lower mortality (p=0.02).Retrospective 1,538 hospitalized patients in Italy, showing only HCQ associated with reduced mortality. Authors analyze mortality amongst those that were alive at day 7 to avoid survival time bias due to drug recording requiring a minimum of 5 days treatment.
Apr 2021, J. Clinical Medicine, https://www.mdpi.com/2077-0383/10/9/1951, https://c19p.org/derosa
104. Alzahrani et al., Clinical characteristics and outcome of COVID-19 in patients with rheumatic diseases
47 patient HCQ prophylaxis study: 59% lower mortality (p=1), 81% lower ventilation (p=0.54), and 33% lower severe cases (p=0.7).Retrospective 47 rheumatic disease patients not finding significant differences with HCQ.
Apr 2021, Rheumatology Int. , https://link.springer.com/article/10.1007/s00296-021-04857-9, https://c19p.org/alzahrani
105. Dev et al., Risk factors and frequency of COVID-19 among healthcare workers at a tertiary care centre in India: a case–control study
759 patient HCQ prophylaxis study: 26% fewer cases (p=0.003).Retrospective case control study of 3,100 healthcare workers in India showing lower cases with HCQ prophylaxis, and an inverse association between the number of HCQ doses taken and the risk of COVID-19 cases. Low risk population with no mortality and no severe cases.
Mar 2021, Transactions of The Royal Society of Tropical Medicine and Hygiene, https://academic.oup.com/trstmh/advance-article/doi/10.1093/trstmh/trab047/6186057, https://c19p.org/dev
106. Taccone et al., The role of organizational characteristics on the outcome of COVID-19 patients admitted to the ICU in Belgium
1,747 patient HCQ ICU study: 25% lower mortality (p=0.02).Retrospective 1,747 ICU patients in Belgium showing lower mortality with HCQ, multivariate mixed effects analysis HCQ aOR 0.64 [0.45-0.92].
Dec 2020, The Lancet Regional Health - Europe, https://www.sciencedirect.com/science/article/pii/S2666776220300193, https://c19p.org/taccone
107. Tan et al., A retrospective comparison of drugs against COVID-19
285 patient HCQ late treatment study: 35% shorter hospitalization (p=0.04).Retrospective 333 patients in China, with only 8 HCQ patients, showing shorter duration of hospitalization with HCQ.
Dec 2020, Virus Research, https://www.sciencedirect.com/science/article/abs/pii/S0168170220311692, https://c19p.org/tan2
108. van Halem et al., Risk factors for mortality in hospitalized patients with COVID-19 at the start of the pandemic in Belgium: a retrospective cohort study
319 patient HCQ late treatment study: 32% lower mortality (p=0.05).Retrospective 319 hospitalized patients in Belgium showing significantly lower mortality with HCQ.
Nov 2020, BMC Infectious Diseases, https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7691970/, https://c19p.org/vanhalem
109. Szente Fonseca et al., Risk of Hospitalization for Covid-19 Outpatients Treated with Various Drug Regimens in Brazil: Comparative Analysis
717 patient HCQ early treatment study: 64% lower hospitalization (p=0.0008).64% lower hospitalization with HCQ. Retrospective 717 patients in Brazil with early treatment, adjusted OR 0.32, p=0.00081, for HCQ versus no medication, and OR 0.45, p=0.0065, for HCQ vs. anything else.
Oct 2020, Travel Medicine and Infectious Disease, https://www.sciencedirect.com/science/article/abs/pii/S1477893920304026, https://c19p.org/fonseca
110. Lammers et al., Early hydroxychloroquine but not chloroquine use reduces ICU admission in COVID-19 patients
1,064 patient HCQ late treatment study: 32% lower combined mortality/ICU admission (p=0.02).Observational study 1,064 hospitalized patients in the Netherlands, 53% reduced risk of transfer to the ICU for mechanical ventilation with HCQ treatment starting on the first day of admission. Weighted propensity score adjusted hazard ratio for transfer to the ICU with HCQ treatment, HR = 0.47, p = 0.008. For CQ, HR = 0.8, p = 0.207. Mortality results in this study are only for mortality before transfer to the ICU. The combined ICU/death HR was 0.68, p = 0.024 for HCQ, and 0.85, p = 0.224 for CQ. Observational, multicenter, cohort study of hospitalized COVID-19 patients. 189 HCQ patients, 377 CQ, 498 control.
Sep 2020, Int. J. Infectious Diseases, https://www.sciencedirect.com/science/article/pii/S1201971220321755, https://c19p.org/lammers
111. Ashinyo et al., Clinical characteristics, treatment regimen and duration of hospitalization among COVID-19 patients in Ghana: a retrospective cohort study
307 patient HCQ late treatment study: 33% shorter hospitalization (p=0.03).Retrospective 307 hospital patients in Ghana showing 33% reduction in hospitalization time with HCQ, 29% reduction with HCQ+AZ, and 37% reduction with CQ+AZ.
Sep 2020, Pan African Medical J., https://www.panafrican-med-journal.com/content/series/37/1/9/full/, https://c19p.org/ashinyo
112. Di Castelnuovo et al., Use of hydroxychloroquine in hospitalised COVID-19 patients is associated with reduced mortality: Findings from the observational multicentre Italian CORIST study
3,451 patient HCQ late treatment study: 30% lower mortality (p<0.0001).Retrospective 3,451 hospitalized patients, 30% reduction in mortality with HCQ after propensity adjustment, HR 0.70 [0.59 - 0.84].
Aug 2020, European J. Internal Medicine, https://www.sciencedirect.com/science/article/abs/pii/S0953620520303356, https://c19p.org/dicastelnuovo
113. Catteau et al., Low-dose Hydroxychloroquine Therapy and Mortality in Hospitalized Patients with COVID-19: A Nationwide Observational Study of 8075 Participants
8,075 patient HCQ late treatment study: 32% lower mortality (p<0.0001).Retrospective 8,075 hospitalized patients, 4,542 low-dose HCQ, 3,533 control. 35% lower mortality for HCQ (17.7% vs. 27.1%), adjusted HR 0.68 [0.62–0.76]. Low-dose HCQ monotherapy was independently associated with lower mortality in hospitalized patients. Patients exposed to others therapies (TCZ, AZ, LPV/RTV) were excluded. Statistical analysis was performed by an independent group. Calendar time of prescription and immortal time bias was taken into account. Corticosteroids prescriptions was low in both groups.
Aug 2020, Int. J. Antimicrobial Agents, https://www.sciencedirect.com/science/article/abs/pii/S0924857920303423, https://c19p.org/catteau
33 patient HCQ late treatment RCT: 24% improved viral clearance (p=0.71).
2 very small studies with hospitalized patients in Taiwan. RCT with 21 treatment and 12 SOC patients. No mortality, or serious adverse effects. Median time to negative RNA 5 days versus 10 days SOC, p=0.4. Risk of PCR+ at day 14, RR 0.76, p = 0.71. Small retrospective study with 12 of 28 HCQ patients and 5 of 9 in the control group being PCR- at day 14, RR 1.29, p = 0.7. The RCT and retrospective study are listed separately [Chen, Chen].
Jul 2020, PLoS ONE, https://journals.plos.org/plosone/article?id=10.1371/journal.pone.0242763, https://c19p.org/chen25
115. Tang et al., Hydroxychloroquine in patients with mainly mild to moderate coronavirus disease 2019: open label, randomised controlled trial
150 patient HCQ late treatment RCT: 21% improved viral clearance (p=0.51).150 patient very late stage RCT showing no significant difference. Treatment was very late, an average of 16.6 days after symptom onset. Data favorable to HCQ was deleted in the second version, see analysis [mediterranee-infection.com]. "[HCQ] accelerate[s] the alleviation of clinical symptoms"; "More rapid alleviation of clinical symptoms with SOC plus HCQ than with SOC alone was observed during the second week since randomization"; "The efficacy of HCQ on the alleviation of symptoms, HR 8.83 [1.09-71.3], was more evident when the confounding effects of other anti-viral agents were removed".
Apr 2020, BMJ 2020, 369, https://www.bmj.com/content/369/bmj.m1849, https://c19p.org/tang
116. Mitjà et al., Hydroxychloroquine for Early Treatment of Adults with Mild Covid-19: A Randomized-Controlled Trial
293 patient HCQ early treatment RCT: 16% lower hospitalization (p=0.64), 34% improved recovery (p=0.38), and 2% improved viral clearance.This paper has conflicting values, table S2 shows 12 control hospitalizations, while table 2 shows 11. The original report for this paper had more conflicting values, with values reported in Table 2 and the abstract corresponding to 12 control hospitalizations, while others corresponded to 11 control hospitalizations. The counts in table S2 also do not match - n=290 is given for secondary endpoints but the three groups add up to n=238. The sum of the secondary endpoint counts for the control group in table 2 do not match the group size. One missing patient may be the 12th control hospitalization but there are 2 more missing. There was a 16% reduction in hospitalization and 34% reduction in the risk of no symptom resolution, without statistical significance due to small samples. Treatment delay is unknown at this time. They report a delay of up to 120 hours after symptoms plus an additional unspecified delay where medication was provided to patients at the first home visit. Authors..
Jul 2020, Clinical Infectious Diseases, ciaa1009, https://academic.oup.com/cid/article/doi/10.1093/cid/ciaa1009/5872589, https://c19p.org/mitja
117. Chechter et al., Evaluation of patients treated by telemedicine in the beginning of the COVID-19 pandemic in São Paulo, Brazil: A non-randomized clinical trial preliminary study
72 patient HCQ early treatment study: 95% lower hospitalization (p=0.004).Prospective study of 187 telemedicine patients in Brazil. 74 presenting with moderate symptoms were offered treatment with HCQ+AZ, 12 did not accept HCQ (taking AZ only), forming a control group. There was lower hospitalization and improved recovery with treatment.
Nov 2021, Heliyon, https://www.sciencedirect.com/science/article/pii/S2405844023025446, https://c19p.org/chechter
118. McCullough et al., Hydroxychloroquine in the Prevention of COVID-19 Infection in Healthcare Workers
221 patient HCQ prophylaxis study: 52% fewer cases (p=0.01).Prospective study with 221 healthcare workers, showing lower risk of COVID-19 with HCQ prophylaxis.
Aug 2021, NCT04333225, https://clinicaltrials.gov/study/NCT04333225, https://c19p.org/mccullough4
119. Modrák et al., Detailed disease progression of 213 patients hospitalized with Covid-19 in the Czech Republic: An exploratory analysis
213 patient HCQ late treatment study: 59% lower mortality (p=0.04).Retrospective 213 hospitalized patients in Czech Republic showing lower mortality with HCQ. Subject to confounding by indication.
Dec 2020, medRxiv, https://www.medrxiv.org/content/10.1101/2020.12.03.20239863v1, https://c19p.org/modrak
120. Khurana et al., Prevalence and clinical correlates of COVID-19 outbreak among healthcare workers in a tertiary level hospital
181 patient HCQ prophylaxis study: 51% fewer cases (p=0.02).Study of hospital health care workers showing HCQ prophylaxis reduces COVID-19 significantly, OR 0.30, p=0.02. 94 positive health care workers with a matched sample of 87 testing negative. Full course prophylaxis was important in this study which used a low dose of 400mg/week HCQ (800mg for week 1), so it may take longer to reach therapeutic levels. Actual benefit of HCQ may be larger because severity of symptoms are not considered here but HCQ may also reduce severity.
Jul 2020, medRxiv, https://www.medrxiv.org/content/10.1101/2020.07.21.20159301v1, https://c19p.org/khurana
121. Membrillo de Novales et al., Early Hydroxychloroquine Is Associated with an Increase of Survival in COVID-19 Patients: An Observational Study
166 patient HCQ late treatment study: 55% lower mortality (p=0.002).166 patients hospitalised with COVID-19, HCQ increased survival 1.4 - 1.8 times when patients admitted in early stages. Early is relative to hospital admission here - all patients were in relatively serious condition.
May 2020, Preprints, https://www.preprints.org/manuscript/202005.0057, https://c19p.org/membrillo
122. Rajasingham et al., Hydroxychloroquine as pre-exposure prophylaxis for COVID-19 in healthcare workers: a randomized trial
1,483 patient HCQ prophylaxis RCT: 27% fewer cases (p=0.07).PrEP RCT showing lower cases with HCQ prophylaxis. The trial was halted after 47% enrollment, p < 0.05 would be reached at ~75% enrollment if similar results continued. HR 0.66/0.68 for full medication adherence, 0.72/0.74, p = 0.18/0.22 overall (1x/2x dosing). Efficacy for first responders was higher, OR 0.32, p = 0.01. First responders had a much higher incidence, allowing greater power, and reducing the effect of confounders such as misdiagnosis of other conditions or survey issues. Performance is similar to the control arm for the first 3 weeks. The effect may be greater with a dosage regimen that achieves therapeutic levels faster [tandfonline.com]. ~40% of participants suspected they might have had COVID-19 before the trial, the effect in people without prior COVID-19 may be higher. Research shows the treatment used in the control arm (folic acid) may have significant efficacy for COVID-19 [Deschasaux-Tanguy, Farag], so the true effectiveness of HCQ may be higher than observed...
Sep 2020, Clinical Infectious Diseases, https://academic.oup.com/cid/advance-article/doi/10.1093/cid/ciaa1571/5929230, https://c19p.org/rajasingham
123. Singh et al., Safety and efficacy of antiviral therapy alone or in combination in COVID-19 - a randomized controlled trial (SEV COVID Trial)
74 patient HCQ late treatment RCT: 48% lower mortality (p=0.45) and 14% improved recovery (p=0.76).Very small early terminated RCT in India, showing lower mortality but without statistical significance with the very small sample size. Time since symptom onset is not provided. The recovery percentage for non-severe group B (86.7%) does not match any number of recoveries, we have used the closest number (15/17).
Jun 2021, medRxiv, https://www.medrxiv.org/content/10.1101/2021.06.06.21258091v1, https://c19p.org/singh2
124. Almazrou et al., Comparing the impact of Hydroxychloroquine based regimens and standard treatment on COVID-19 patient outcomes: A retrospective cohort study
161 patient HCQ late treatment study: 65% lower ventilation (p=0.16) and 21% lower ICU admission (p=0.78).Retrospective 161 hospitalized patients in Saudi Arabia showing lower ventilation and ICU admission with HCQ, but not statistically significant with the small sample sizes.
Sep 2020, Saudi Pharmaceutical J., https://www.sciencedirect.com/science/article/pii/S1319016420302334, https://c19p.org/almazrou
125. Gentry et al., Long-term hydroxychloroquine use in patients with rheumatic conditions and development of SARS-CoV-2 infection: a retrospective cohort study
32,109 patient HCQ prophylaxis study: 91% lower mortality (p=0.1) and 21% fewer cases (p=0.27).Retrospective patients with rheumatologic conditions showing zero of 10,703 COVID-19 deaths for HCQ patients versus 7 of 21,406 propensity matched control patients (not statistically significant). The average age of HCQ patients is slightly lower 64.8 versus 65.4 control. COVID-19 cases OR 0.79, p=0.27. There are several significant differences in the propensity matched patients that could affect results, e.g., 20.9% SLE versus 24.7%.
Sep 2020, Lancet Rheumatology, https://www.thelancet.com/journals/lanrhe/article/PIIS2665-9913(20)30305-2/fulltext, https://c19p.org/gentry
840 patient HCQ late treatment study: 78% lower mortality (p<0.0001).
Retrospective 750 COVID-19 patients in Saudi Arabia, showing lower mortality with HCQ treatment in unadjusted results. Authors note that the poor results in some other trials may be related to increased dosages and later treatment.
Apr 2023, J. Multidisciplinary Healthcare, https://www.dovepress.com/profiles-of-independent-comorbidity-groups-in-senior-covid-19-patients-peer-reviewed-fulltext-article-JMDH, https://c19p.org/said2
127. Satti et al., Characteristics and Obstetric Outcomes in Women With Autoimmune Rheumatic Disease During the COVID-19 Pandemic in Qatar
80 patient HCQ prophylaxis study: 61% fewer cases (p=0.04).Retrospective 80 consecutive pregnant patients with autoimmune rheumatic diseases in Qatar, showing lower risk of COVID-19 cases with HCQ prophylaxis.
Apr 2022, Cureus, https://www.cureus.com/articles/91696-characteristics-and-obstetric-outcomes-in-women-with-autoimmune-rheumatic-disease-during-the-covid-19-pandemic-in-qatar, https://c19p.org/satti
128. AbdelGhaffar et al., Prediction of mortality in hospitalized Egyptian patients with Coronavirus disease-2019: A multicenter retrospective study
3,712 patient HCQ late treatment study: 100% lower mortality (p<0.0001).Retrospective 3,712 hospitalized patients in Egypt, showing lower mortality with HCQ treatment in unadjusted results. According to the official treatment protocol, HCQ was recommended with higher risk and/or more serious cases.
Jan 2022, PLOS ONE, https://journals.plos.org/plosone/article?id=10.1371/journal.pone.0262348, https://c19p.org/abdelghaffar
129. Huang et al., Clinical characteristics of 17 patients with COVID-19 and systemic autoimmune diseases: a retrospective study
1,255 patient HCQ prophylaxis study: 80% lower hospitalization (p=0.001).Analysis of 1255 COVID-19 patients in Wuhan Tongji Hospital finding 0.61% with systemic autoimmune diseases, much lower than authors expected (3%-10%). Authors hypothesise that protective factors, such as CQ/HCQ use, reduce hospitalization.
Jun 2020, Annals of the Rheumatic Diseases, https://ard.bmj.com/content/79/9/1163, https://c19p.org/huangard
130. Oku et al., Risk factors for hospitalization or mortality for COVID-19 in patients with rheumatic diseases: Results of a nation-wide JCR COVID-19 registry in Japan
220 patient HCQ prophylaxis study: 92% lower mortality (p=1) and 12% lower hospitalization (p=0.34).Retrospecttive 220 COVID-19 patients with rheumatic disease in Japan, showing lower mortality and hospitalization with HCQ prophylaxis, without statistical significance.
Sep 2022, Modern Rheumatology, https://academic.oup.com/mr/advance-article/doi/10.1093/mr/roac104/6692611, https://c19p.org/oku
131. Ramírez-García et al., Hydroxychloroquine and Tocilizumab in the Treatment of COVID-19: A Longitudinal Observational Study
403 patient HCQ late treatment study: 67% lower mortality (p<0.0001) and 6% higher ICU admission (p=1).Retrospective 403 hospitalized patients in Spain, showing lower mortality with treatment, however authors do not adjust for the differences between the groups. Confounding by indication is likely.
May 2021, Archivos de Medicina Universitaria, https://digibug.ugr.es/handle/10481/69170, https://c19p.org/ramirezgarcia
3,885 patient HCQ late treatment study: 36% lower mortality (p=0.005).
Retrospective 352 hospitalized COVID-19 patients in Belgium and 3,533 control patients from the contemporaneous Belgian Collaborative Group, showing significantly lower mortality with HCQ treatment. The survival benefit was consistent in all age groups. No torsade de pointes or ventricular arrhythmias were observed. Mean time from onset is not provided, but 43% of patients with known onset were admitted within 5 days, making the efficacy consistent with expectations based on the treatment delay [c19hcq.org]. HCQ 800mg day one, 200mg bid for five days, according to national guidelines. Authors note that the poor results in SOLIDARITY/RECOVERY may be related to the excessively high doses used. Most patients also received AZ. Adjusted results are only provided for all HCQ patients. Publication was delayed over 3 years. Authors reported in 2021 that the paper had been rejected by the editors of four different journals, without peer review [twitter.com].
Sep 2023, New Microbes and New Infections, https://www.sciencedirect.com/science/article/pii/S2052297523000914, https://c19p.org/meeus
133. Johnston et al., Hydroxychloroquine with or Without Azithromycin for Treatment of Early SARS-CoV-2 Infection Among High-Risk Outpatient Adults: A Randomized Clinical Trial
231 patient HCQ late treatment RCT: 30% lower hospitalization (p=0.73), 2% improved recovery (p=0.95), and 29% faster viral clearance.Small early terminated late treatment RCT comparing vitamin C + folic acid, HCQ + folic acid, and HCQ+AZ, showing non-statistically significantly lower hospitalization with HCQ/HCQ+AZ, and faster viral clearance with HCQ. Enrollment was a median of 5.9 days after onset (6.2 and 6.3 in the treatment arms). The median time to viral clearance for vitamin C + folic acid was 8 days in the preprint but changed to 7 days in the published paper without explanation. Both vitamin C [c19early.org] and folic acid [Deschasaux-Tanguy, Farag] show efficacy in other trials, so the true effectiveness of HCQ(+AZ) may be higher than observed. Low risk patients, median age 37, no deaths (not matching the title which claims "high risk"). There was a post hoc addition of a new cycle threshold that obscures the statistically significant faster clearance. There was no analysis for time from symptom onset. Authors identify (relatively) low and high risk cohorts, but do not provide either viral..
Dec 2020, eClinicalMedicine, https://www.thelancet.com/journals/eclinm/article/PIIS2589-5370(21)00053-5/fulltext, https://c19p.org/johnston
134. Alshamrani et al., Comprehensive evaluation of six interventions for hospitalized patients with COVID-19: A propensity score matching study
814 patient HCQ late treatment PSM study: 50% lower mortality (p=0.18), 37% lower progression (p=0.21), 9% shorter ICU admission (p=0.66), and 3% longer hospitalization (p=0.7).PSM retrospective 29 hospitals in Saudi Arabia, finding lower mortality with HCQ, without reaching statistical significance (described by authors as "no impact").
Feb 2023, Saudi Pharmaceutical J., https://www.sciencedirect.com/science/article/pii/S1319016423000348, https://c19p.org/alshamrani
135. Avezum et al., Hydroxychloroquine versus placebo in the treatment of non-hospitalised patients with COVID-19 (COPE – Coalition V): A double-blind, multicentre, randomised, controlled trial
1,372 patient HCQ early treatment RCT: 1% lower mortality (p=1), 32% higher ventilation (p=0.79), 16% lower ICU admission (p=0.61), and 23% lower hospitalization (p=0.18).Authors have not responded to a request for the data. Outpatient RCT with 687 HCQ and 682 control patients in Brazil, showing lower hospitalization with treatment, not reaching statistical significance. Higher efficacy was seen with treatment <4 days from onset, RR 0.61. The associated meta analysis includes mostly late treatment studies, for example in [Schwartz] the median delay from onset was 7 days. [Omrani] is missing. The values for [Johnston] are incorrect - the study shows 4 hospitalizations in the control arm - RR for this study should be 0.58 instead of 0.78.
Mar 2022, The Lancet Regional Health - Americas, https://www.sciencedirect.com/science/article/pii/S2667193X22000606, https://c19p.org/avezum
136. Delgado et al., Investigational medications in 9,638 hospitalized patients with severe COVID-19: lessons from the “fail-and-learn” strategy during the first two waves of the pandemic in 2020
9,638 patient HCQ late treatment study: 26% lower mortality (p=0.002).PSM retrospective 9,638 patients in the USA, showing significantly lower mortality with HCQ in early 2020 (1,157 HCQ patients), and no significant difference in late 2020 (82 HCQ patients). The few patients treated in the later period may be in more serious condition due to the effort required to overcome the politicization and censorship in the study country. Authors refer to their result as "no relevant benefit in mortality between the two surges".
Feb 2023, Research Square, https://www.researchsquare.com/article/rs-2596201/v1, https://c19p.org/delgado
137. Brouqui et al., SARS-CoV 2 Viral Clearance in 1276 Patients: Associated Factors and the Role of Treatment with Hydroxychloroquine and Azithromycin
1,276 patient HCQ late treatment study: 15% improved viral clearance (p=0.04).Retrospective 1,276 hospitalized patients showing significantly faster viral clearance with HCQ. Authors also perform a meta-analysis of 9 studies, with 1,461 HCQ-treated patients and 958 controls, showing significantly faster viral clearance with HCQ on day 7.
Jul 2024, Acta Scientific Microbiology, https://actascientific.com/ASMI/pdf/ASMI-07-1413.pdf, https://c19p.org/brouqui4
138. AlShehhi et al., Utilizing machine learning for survival analysis to identify risk factors for COVID-19 intensive care unit admission: A retrospective cohort study from the United Arab Emirates
1,797 patient HCQ late treatment study: 43% lower ICU admission (p=0.001).Retrospective 1,787 hospitalized COVID-19 patients in the United Arab Emirates, identifying hydroxychloroquine as reducing the risk of ICU admission in a machine learning model. Only unadjusted quantitative results are provided, which also show a benefit.
Jan 2024, PLOS ONE, https://journals.plos.org/plosone/article?id=10.1371/journal.pone.0291373, https://c19p.org/alshehhi
139. Sahebari et al., Influence of biologic and conventional disease-modifying antirheumatic drugs on COVID-19 incidence among rheumatic patients during the first and second wave of the pandemic in Iran
512 patient HCQ prophylaxis study: 56% fewer cases (p=0.02).Retrospective 512 rheumatic disease patients in Iran, showing lower risk of COVID-19 with HCQ use.
Sep 2022, Reumatologia/Rheumatology, https://www.termedia.pl/doi/10.5114/reum.2022.119039, https://c19p.org/sahebari
140. MacFadden et al., Screening Large Population Health Databases for Potential COVID-19 Therapeutics: A Pharmacopeia-Wide Association Study (PWAS) of Commonly Prescribed Medications
HCQ prophylaxis study: 12% fewer cases (p=0.01).Retrospective 26,121 cases and 2,369,020 controls ≥65yo in Canada, showing lower cases with chronic use of HCQ.
Mar 2022, Open Forum Infectious Diseases, https://academic.oup.com/ofid/advance-article/doi/10.1093/ofid/ofac156/6555707, https://c19p.org/macfadden
141. Ahmed et al., Factors Affecting the Incidence, Progression, and Severity of COVID-19 in Type 1 Diabetes Mellitus
100 patient HCQ prophylaxis study: 99% fewer cases (p=0.08).Retrospective type 1 diabetes patients in Saudi Arabia showing reduced risk of cases with HCQ prophylaxis.
Nov 2021, BioMed Research Int., https://www.hindawi.com/journals/bmri/2021/1676914/, https://c19p.org/ahmed2
142. Shaw et al., COVID-19 in Individuals Treated With Long-Term Hydroxychloroquine: A Propensity Score-Matched Analysis of Cicatricial Alopecia Patients
144 patient HCQ prophylaxis PSM study: 13% fewer cases (p=0.006).PSM retrospective 144 alopecia patients in the USA, showing lower risk of COVID-19 with HCQ prophylaxis. The supplemental appendix is not available.
Jun 2021, J. Drugs in Dermatology, https://jddonline.com/articles/dermatology/S1545961621P0914X, https://c19p.org/shaw
143. Barry et al., Clinical Characteristics and Outcomes of Hospitalized COVID-19 Patients in a MERS-CoV Referral Hospital during the Peak of the Pandemic
605 patient HCQ late treatment study: 99% lower mortality (p=0.6).605 hospitalized patients in Saudi Arabia showing no mortality with HCQ (only 6 patients received HCQ).
Mar 2021, Int. J. Infectious Diseases, https://www.sciencedirect.com/science/article/pii/S1201971221002769, https://c19p.org/barry
144. Güner et al., Comparing ICU Admission Rates of Mild/Moderate COVID-19 Patients Treated with Hydroxychloroquine, Favipiravir, and Hydroxychloroquine plus Favipiravir
704 patient HCQ late treatment study: 77% lower ICU admission (p=0.16).Retrospective 824 hospitalized patients in Turkey showing lower ICU admission for HCQ vs. favipiravir.
Dec 2020, J. Infection and Public Health, https://www.sciencedirect.com/science/article/pii/S1876034120307735, https://c19p.org/guner
145. Falcone et al., Role of low-molecular weight heparin in hospitalized patients with SARS-CoV-2 pneumonia: a prospective observational study
315 patient HCQ late treatment PSM study: 65% lower mortality (p=0.2).Prospective observational study of 315 hospitalized patients in Italy showing 65% lower mortality with HCQ. The median treatment delay was 6 days for survivors and 6.5 days for non-survivors. Mortality relative risk: RR 0.35, p = 0.2, propensity score matched RR 0.75, p = 0.36, multivariate Cox regression RR 0.43, p < 0.001, univariate Cox regression
Nov 2020, Open Forum Infectious Diseases, https://academic.oup.com/ofid/advance-article/doi/10.1093/ofid/ofaa563/5992463, https://c19p.org/falcone
146. Boari et al., Prognostic factors and predictors of outcome in patients with COVID-19 and related pneumonia: a retrospective cohort study
258 patient HCQ late treatment study: 55% lower mortality (p=0.001).Retrospective 258 hospitalized patients in Italy showing lower mortality with HCQ treatment, unadjusted relative risk RR 0.455, p<0.001. Data is in the supplementary appendix.
Nov 2020, Bioscience Reports, https://portlandpress.com/bioscirep/article/doi/10.1042/BSR20203455/226985, https://c19p.org/boari
147. Águila-Gordo et al., Mortality and associated prognostic factors in elderly and very elderly hospitalized patients with respiratory disease COVID-19
416 patient HCQ late treatment study: 67% lower mortality (p=0.1).67% lower mortality with HCQ. Retrospective 416 elderly patients in Spain showing adjusted HCQ mortality hazard ratio HR 0.33, p = 0.1.
Nov 2020, Revista Española de Geriatría y Gerontología, https://www.sciencedirect.com/science/article/pii/S0211139X20301748, https://c19p.org/aguilagordo
148. Coll et al., Covid-19 in transplant recipients: the spanish experience
635 patient HCQ late treatment study: 46% lower mortality (p<0.0001).Retrospective 652 transplant recipient patients in Spain showing 46% lower mortality for patients treated with HCQ, unadjusted relative risk RR 0.54, p<0.0001.
Oct 2020, American J. Transplantation, https://onlinelibrary.wiley.com/doi/abs/10.1111/ajt.16369, https://c19p.org/coll
149. Grau-Pujol et al., Pre-exposure prophylaxis with hydroxychloroquine for COVID-19: a double-blind, placebo-controlled randomized clinical trial
269 patient HCQ prophylaxis RCT: 11% fewer cases (p=1).Small PrEP RCT showing that PrEP with HCQ is safe at the dosage used. There were no deaths, hospitalizations, or serious adverse events. The paper states: "Among all trial participants at the end of the first month (n=253), only one participant from the placebo arm (1/116, 0.8%), tested positive for SARS-CoV-2 PCR and for a SARS-CoV-2 serology test". The abstract states: "only one participant in each group was diagnosed with COVID-19".
Sep 2020, Trials, https://trialsjournal.biomedcentral.com/articles/10.1186/s13063-021-05758-9, https://c19p.org/graupujol
150. Berenguer et al., Characteristics and predictors of death among 4035 consecutively hospitalized patients with COVID-19 in Spain
3,995 patient HCQ late treatment study: 18% lower mortality (p=0.0001).Retrospective 4035 hospitalized patients in Spain showing reduced mortality with HCQ (data is in the supplementary appendix).
Aug 2020, Clinical Microbiology and Infection, https://www.clinicalmicrobiologyandinfection.com/article/S1198-743X(20)30431-6/fulltext, https://c19p.org/berenguer
151. Faíco-Filho et al., No benefit of hydroxychloroquine on SARS-CoV-2 viral load reduction in non-critical hospitalized patients with COVID-19
66 patient HCQ late treatment study: 81% improved viral reduction rate (p=0.4).Viral load comparison for 34 HCQ and 32 control patients hospitalized with moderate COVID-19. All patients recovered limiting the room for beneficial effects. While not achieving statistical significance, results show faster recovery with HCQ. The greatest benefit is seen mid-recovery as expected for an effective treatment: Δt7-12: 81% improvement with HCQ Δt<7: 24% improvement with HCQ For Δt>12, everyone has recovered so there is no room for improvement. Since the HCQ group started slightly higher the improvement is slightly less. Most participants have also dropped out by this test, with only 6 HCQ and 9 control remaining (also suggesting HCQ patients recovered faster).
Jun 2020, Braz J Microbiol, https://link.springer.com/article/10.1007/s42770-020-00395-x, https://c19p.org/faicofilho
152. Mathew et al., Predictors of COVID-19 severity and outcomes in Indian patients with rheumatic diseases: a prospective cohort study
64 patient HCQ prophylaxis study: 20% lower mortality (p=0.8), no change in hospitalization (p=0.94), and 40% lower severe cases (p=0.37).Prospective study of 64 rheumatic disease patients with COVID-19, showing no significant difference in outcomes with HCQ use.
Feb 2023, Rheumatology Advances in Practice, https://academic.oup.com/rheumap/advance-article/doi/10.1093/rap/rkad025/7059537, https://c19p.org/mathew
153. Alqatari et al., COVID-19 in patients with rheumatological diseases in the Eastern Province of Saudi Arabia
34 patient HCQ prophylaxis study: 89% lower ventilation (p=0.13), 64% lower ICU admission (p=0.14), and 64% lower severe cases (p=0.14).Retrospective 34 rheumatological disease patients with COVID-19 in Saudi Arabia, showing lower risk of severe cases with HCQ use in unadjusted results, without statistical significance.
May 2023, J. Medicine and Life, https://europepmc.org/article/PMC/PMC10478665, https://c19p.org/alqatari
154. Raabe et al., Hydroxychloroquine pre-exposure prophylaxis to prevent SARS-CoV-2 among health care workers at risk for SARS-CoV-2 exposure: A nonrandomized controlled trial
130 patient HCQ prophylaxis study: 82% fewer symptomatic cases (p=0.17).Small prophylaxis study with 130 healthcare workers in the USA, showing lower symptomatic cases with HCQ prophylaxis, without statistical significance. HCQ participants were significantly older. The only symptomatic HCQ patient reported headache only as a potential COVID-19 symptom.
Jul 2022, medRxiv, https://www.medrxiv.org/content/10.1101/2022.07.01.22277058, https://c19p.org/raabe
155. Sawanpanyalert et al., Assessment of outcomes following implementation of antiviral treatment guidelines for COVID-19 during the first wave in Thailand
HCQ early treatment study: 42% lower progression (p=0.37).Retrospective 744 hospitalized patients in Thailand, showing lower risk of a poor outcome for favipiravir treatment within 4 days of symptom onset. Early treatment with CQ/HCQ and lopinavir/ritonavir or darunavir/ritonavir also showed lower risk, but without statistical significance. Sample sizes for the number of patients treated within 4 days of symptom onset are not provided.
Sep 2021, Southeast Asian J. Tropical Medicine and Public Health, https://journal.seameotropmednetwork.org/index.php/jtropmed/article/view/490, https://c19p.org/sawanpanyalert
208 patient HCQ late treatment study: 44% lower mortality (p=0.14) and 3% improved recovery (p=0.91).
Retrospective 208 hospitalized COVID-19 patients in Burkina Faso showing lower mortality with HCQ/CQ+AZ treatment, without statistical significance. There was no difference for recovery.
Feb 2021, J. Infectious Diseases and Epidemiology, https://www.clinmedjournals.org/articles/jide/journal-of-infectious-diseases-and-epidemiology-jide-7-192.php?jid=jide, https://c19p.org/baguiya
157. Lano et al., Risk factors for severity of COVID-19 in chronic dialysis patients from a multicentre French cohort
122 patient HCQ late treatment study: 33% lower mortality (p=0.28) and 39% lower combined mortality/ICU admission (p=0.23).33% lower mortality with HCQ+AZ, p=0.28. Retrospective 122 French dialysis patients. 69% lower combined mortality/ICU, p=0.11, for the subgroup not requiring O2 on diagnosis (slightly earlier treatment).
Oct 2020, Clinical Kidney J., October 2020, 878–888, https://academic.oup.com/ckj/article/13/5/878/5934808, https://c19p.org/lano
158. Nachega et al., Clinical Characteristics and Outcomes of Patients Hospitalized for COVID-19 in Africa: Early Insights from the Democratic Republic of the Congo
766 patient HCQ late treatment study: 28% lower mortality (p=0.17) and 26% greater improvement (p=0.13).Retrospective 766 hospitalized patients in DRC showing mortality reduced from 29% to 11%, and improvement at 30 days increased from 65% to 84%. Mortality cox regression adjusted hazard ratio aHR 0.26, p < 0.001 Risk of no improvement adjusted odds ratio aOR 0.28, p < 0.001 Using marginal structural model analysis these risks became: Mortality MSM adjusted odds ratio aOR 0.65, p = 0.166 Risk of no improvement MSM adjusted odds ratio aOR = 0.65, p = 0.132 Median age 46, 630 treated with CQ+AZ.
Oct 2020, The American J. Tropical Medicine and Hygiene, https://www.ajtmh.org/content/journals/10.4269/ajtmh.20-1240, https://c19p.org/nachega
159. Kirenga et al., Characteristics and outcomes of admitted patients infected with SARS-CoV-2 in Uganda
56 patient HCQ early treatment study: 26% faster recovery (p=0.2).Prospective 56 patients in Uganda, 29 HCQ and 27 control, showing 25.6% faster recovery with HCQ, 6.4 vs. 8.6 days (p = 0.20). There was no ICU admission, mechanical ventilation, or death. Treatment delay is not specified but at least a portion of patients appear to have been treated early.
Sep 2020, BMJ Open Respiratory Research, https://bmjopenrespres.bmj.com/content/7/1/e000646, https://c19p.org/kirenga
160. Byakika-Kibwika et al., Safety and Efficacy of Hydroxychloroquine for Treatment of Non-Severe COVID-19 in Adults in Uganda: A Randomized Open Label Phase II Clinical Trial
105 patient HCQ late treatment RCT: no change in recovery (p=0.91) and 29% improved viral clearance (p=0.47).Small 105 patient RCT in Uganda showing no significant differences. No mortality was reported. The patients were very young (median age 32), recovering in a median time of 3 days with standard of care, so there is little room for a treatment to make improvements. Time since symptom onset is not specified, but the distribution of symptoms at baseline suggests that the enrollment is relatively late within a cohort of low risk patients.
Jun 2021, Research Square, https://www.researchsquare.com/article/rs-506195/v1, https://c19p.org/byakikakibwika
161. Budhiraja et al., Clinical Profile of First 1000 COVID-19 Cases Admitted at Tertiary Care Hospitals and the Correlates of their Mortality: An Indian Experience
976 patient HCQ late treatment study: 65% lower mortality (p<0.0001).Retrospective 976 hospitalized patients with 834 treated with HCQ+AZ showing HCQ mortality relative risk RR 0.35, p < 0.0001. Note that in this case HCQ was recommended for mild/moderate cases, so more severe cases may not have received HCQ (which may also be why they became severe cases). We note that this is opposite to a common bias in HCQ studies - in many cases HCQ was more likely to be given to more severe cases.
Nov 2020, medRxiv, https://www.medrxiv.org/content/10.1101/2020.11.16.20232223v1, https://c19p.org/budhiraja
162. Aparisi et al., Low-density lipoprotein cholesterol levels are associated with poor clinical outcomes in COVID-19
654 patient HCQ late treatment study: 63% lower mortality (p=0.008).Retrospective 654 hospitalized patients focused on low-density lipoprotein cholesterol levels, also showing results for HCQ with 605 HCQ patients, unadjusted 30 day mortality relative risk RR 0.37, p = 0.008.
Oct 2020, medRxiv, https://www.medrxiv.org/content/10.1101/2020.10.06.20207092v1, https://c19p.org/aparisi
163. Belmont et al., COVID-19 PrEP HCW HCQ Study
80 patient HCQ prophylaxis study: 79% fewer symptomatic cases (p=0.21).Prospective study of HCQ prophylaxis in the USA, with 56 HCQ patients and 24 control patients, showing no significant differences. NCT04354870
Oct 2021, ClinicalTrials.gov, NCT04354870, https://clinicaltrials.gov/ct2/show/results/NCT04354870, https://c19p.org/belmont
164. Agarwal et al., Low dose hydroxychloroquine prophylaxis for COVID-19 - a prospective study
484 patient HCQ prophylaxis study: 27% lower progression (p=0.21) and 5% more cases (p=0.81).Small prophylaxis trial with 29 low dose HCQ and 455 control healthcare workers in India, showing no statistically significant differences.
Sep 2021, medRxiv, https://www.medrxiv.org/content/10.1101/2021.09.13.21262971v1, https://c19p.org/agarwal2
165. Değirmenci et al., Is vitamin D level important in pregnant women with COVID-19?
125 patient HCQ late treatment study: 43% lower hospitalization (p=0.76).Retrospective 125 pregnant women hospitalized with COVID-19 in Turkey, showing no significant difference in hospitalization length with HCQ, and longer hospitalization with lopinavir/ritonavir use.
Jul 2024, J. Controversies in Obstetrics & Gynecology and Pediatrics, http://journal-jcogp.com/Publication/DisplayArticle/27358, https://c19p.org/degirmencih
166. Scirocco et al., COVID-19 prognosis in systemic lupus erythematosus compared with rheumatoid arthritis and spondyloarthritis: results from the CONTROL-19 Study by the Italian Society for Rheumatology
627 patient HCQ prophylaxis study: 41% lower combined mortality/intubation (p=0.38).Retrospective 103 SLE and 524 RA patients in Italy, showing significantly lower mortality/ventilation with HCQ use for SLE patients, and no significant difference for RA patients in unadjusted results. Authors did not include HCQ in multivariable analysis, only including four variables "chosen among the most clinically relevant". Multivariable analysis may significantly improve results for RA patients because HCQ use may correlate with more severe disease due to use for patients that failed or do not tolerate first-line therapies. It is not clear how the patients were selected - the very high ~25% ventilation/mortality suggests that most were hospitalized COVID-19 patients, in which case any benefit of HCQ in reducing hospitalizations will not be reflected in the results. Authors falsely state that "subsequent studies have definitely proved that [HCQ] is not linked to COVID-19 prognosis", suggesting significant bias, and possibily indicating why HCQ..
Oct 2023, Lupus Science & Medicine, https://lupus.bmj.com/lookup/doi/10.1136/lupus-2023-000945, https://c19p.org/scirocco
167. Sen et al., Post-COVID-19 condition in patients with autoimmune rheumatic diseases: the COVID-19 Vaccination in Autoimmune Diseases (COVAD) study
HCQ long COVID study: 40% lower PASC (p=0.08).Retrospective 755 autoimmune rheumatic disease patients, showing lower risk of PASC (long COVID) with HCQ use, without statistical significance.
Apr 2023, The Lancet Rheumatology, https://www.sciencedirect.com/science/article/pii/S2665991323000668, https://c19p.org/sen2
168. Krishnan et al., Predictors of Mortality among Patients Hospitalized with COVID-19 during the First Wave in India: A Multisite Case-Control Study
2,431 patient HCQ late treatment study: 40% lower mortality (p=0.05).Case control study with 2,431 hospitalized COVID-19 patients in India, showing lower mortality with HCQ treatment, without statistical significance.
Apr 2023, The American J. Tropical Medicine and Hygiene, https://www.ajtmh.org/view/journals/tpmd/108/4/article-p727.xml, https://c19p.org/krishnan2
169. Aweimer et al., Mortality rates of severe COVID-19-related respiratory failure with and without extracorporeal membrane oxygenation in the Middle Ruhr Region of Germany
149 patient HCQ ICU study: 40% lower mortality (p=0.12).Retrospective 149 patients under invasive mechanical ventilation in Germany showing no significant difference in mortality with HCQ in unadjusted results.
Mar 2023, Scientific Reports, https://www.nature.com/articles/s41598-023-31944-7, https://c19p.org/aweimerh
170. Chevalier et al., CovAID: Identification of factors associated with severe COVID-19 in patients with inflammatory rheumatism or autoimmune diseases
1,213 patient HCQ prophylaxis study: 35% lower mortality (p=0.19) and 19% lower hospitalization (p=0.36).Retrospective 1,213 rheumatic disease patients in France, showing lower risk of mortality and severe cases with HCQ use in univariate analysis, without statistical significance.
Mar 2023, Frontiers in Medicine, https://www.frontiersin.org/articles/10.3389/fmed.2023.1152587/full, https://c19p.org/chevalier
171. Opdam et al., Identification of Risk Factors for COVID-19 Hospitalization in Patients with Anti-Rheumatic Drugs: Results from a Multicenter Nested Case Control Study
477 patient HCQ prophylaxis study: 45% lower hospitalization (p=0.18).Retrospective 81 cases and 396 controls among rheumatic disease patients in the Netherlands, showing lower risk of hospitalization with HCQ prophylaxis, without statistical significance.
Feb 2022, Clinical Pharmacology & Therapeutics, https://ascpt.onlinelibrary.wiley.com/doi/10.1002/cpt.2551, https://c19p.org/opdam
172. Cordtz et al., Incidence of COVID-19 Hospitalisation in Patients with Systemic Lupus Erythematosus: A Nationwide Cohort Study from Denmark
2,533 patient HCQ prophylaxis study: 40% lower hospitalization (p=0.39).Retrospective 2,533 SLE patients in Denmark showing no significant difference in hospitalization risk for COVID-19 cases with HCQ treatment.
Aug 2021, J. Clinical Medicine, https://www.mdpi.com/2077-0383/10/17/3842, https://c19p.org/cordtz2
173. Li et al., Evaluation of the efficacy and safety of hydroxychloroquine in comparison with chloroquine in moderate and severe patients with COVID-19
28 patient HCQ late treatment study: 50% higher hospital discharge (p=0.09).Small RCT comparing HCQ and CQ in China with 88 very late stage (17.6 days from onset to hospitalization and ~10 days to randomization) patients. The primary clinical outcomes (TTCR and TTCI) were not significantly different. Authors note that HCQ may have more promising efficacy in immune system modulation, indicated by ferritin reduction in the moderate cases and improvement of CT scores and lymphocyte counts in the severe cases. HCQ and CQ were well tolerated. Authors also compare RCT patients to a matched sample of non-RCT patients in the same hospital, showing shorter time to discharge with CQ/HCQ, but not statistically significant due to the small size.
Jan 2021, Science China Life Sciences, https://link.springer.com/article/10.1007/s11427-020-1871-4, https://c19p.org/li3
174. Matangila et al., Clinical characteristics of COVID-19 patients hospitalized at Clinique Ngaliema, a public hospital in Kinshasa, in the Democratic Republic of Congo: A retrospective cohort study
160 patient HCQ late treatment study: 55% lower mortality (p=0.21).55% lower death with HCQ+AZ. Retrospective 160 hospitalized patients in the Democratic Republic of Congo, 92% receiving HCQ+AZ, showing adjusted OR 0.24 [0.03-2.2].
Dec 2020, PLoS ONE, https://journals.plos.org/plosone/article?id=10.1371/journal.pone.0244272, https://c19p.org/matangila
1,150 patient HCQ late treatment study: 44% lower mortality (p=0.14).
Retrospective 1210 hospitalized patients in Turkey focused on chronic kidney disease, haemodialysis and renal transplant patients, but also showing lower mortality with HCQ. Subject to confounding by indication.
Dec 2020, Nephrology Dialysis Transplantation, https://academic.oup.com/ndt/article/35/12/2083/6020341, https://c19p.org/ozturk
176. Serrano et al., COVID-19 and lung cancer: What do we know?
22 patient HCQ late treatment study: 43% lower mortality (p=0.15).Small retrospective study of 22 lung cancer patients, 14 treated with HCQ+AZ, showing HCQ+AZ mortality relative risk RR 0.57, p = 0.145.
Sep 2020, Ann. Oncol., 2020, Sep, 31, S1026, https://www.annalsofoncology.org/article/S0923-7534(20)41826-5/fulltext, https://c19p.org/serrano
177. Bousquet et al., ADL-dependency, D-Dimers, LDH and absence of anticoagulation are independently associated with one-month mortality in older inpatients with Covid-19
108 patient HCQ late treatment study: 43% lower mortality (p=0.15).Observational prospective 108 hospitalized patients 65 and older, showing HCQ mortality OR 0.49, p = 0.15.
Jun 2020, Aging, 11306-11313, https://www.aging-us.com/article/103583/text, https://c19p.org/bousquet
178. Fontana et al., SARS-CoV-2 infection in dialysis patients in northern Italy: a single-centre experience
15 patient HCQ late treatment study: 50% lower mortality (p=0.53).Very small observational study of 15 dialysis patients showing HCQ mortality RR 0.50, p = 0.53.
Jun 2020, Clinical Kidney J., 334–339, https://academic.oup.com/ckj/article/13/3/334/5860798, https://c19p.org/fontana
179. Alberici et al., A report from the Brescia Renal COVID Task Force on the clinical characteristics and short-term outcome of hemodialysis patients with SARS-CoV-2 infection
94 patient HCQ late treatment study: 43% lower mortality (p=0.12).Analysis of 94 hemodialysis COVID-19 positive patients, showing lower mortality with HCQ treatment, not reaching statistical significance.
May 2020, Kidney Int., 20-26, July 1, 2020, https://www.kidney-international.org/article/S0085-2538(20)30508-1/fulltext, https://c19p.org/alberici
180. Frontera et al., Treatment with Zinc is Associated with Reduced In-Hospital Mortality Among COVID-19 Patients: A Multi-Center Cohort Study
3,473 patient HCQ late treatment PSM study: 37% lower mortality (p=0.02).Retrospective 3,473 hospitalized patients showing lower mortality with HCQ+zinc.
Oct 2020, Research Square, https://www.researchsquare.com/article/rs-94509/v1, https://c19p.org/frontera
181. Omma et al., Hydroxychloroquine shortened hospital stay and reduced intensive care unit admissions in hospitalized COVID-19 patients
393 patient HCQ late treatment study: 28% lower mortality (p=0.3), 50% lower ICU admission (p=0.004), and 17% shorter hospitalization (p=0.007).Retrospective 393 hospitalized COVID-19 patients in Turkey, showing lower ICU admission and shorter hospitalization time with HCQ. There was no significant difference for mortality. Severity was higher in the HCQ group with greater baseline ventilation, high flow oxygen, fever, and dyspnea.
Jan 2022, The J. Infection in Developing Countries, https://jidc.org/index.php/journal/article/view/14933, https://c19p.org/omma
182. Patil et al., A Prospective Longitudinal Study Evaluating The Influence of Immunosuppressives and Other Factors On COVID-19 in Autoimmune Rheumatic Diseases
9,212 patient HCQ prophylaxis study: 66% lower mortality (p=0.1) and 9% fewer cases (p=0.43).Prospective study of 9,212 autoimmune rheumatic disease patients showing lower mortality with HCQ, without reaching statistical significance. Authors incorrectly state "HCQ use did not influence occurrence of COVID-19 (RR = 0.909, CI (0.715,1.154), p = 0.432) or mortality (p = 0.097)" [nature.com]. CFR for the autoimmune rheumatic disease patients was 4.6 times higher than in the general population from the same area.
Aug 2021, Research Square, https://www.researchsquare.com/article/rs-805748/v1, https://c19p.org/patil
183. Mehrizi et al., Drug prescription patterns and their association with mortality and hospitalization duration in COVID-19 patients: insights from big data
917,198 patient HCQ late treatment study: 26% lower mortality (p<0.0001).Retrospective study of 917,198 hospitalized COVID-19 cases covered by the Iran Health Insurance Organization over 26 months showing that antithrombotics, corticosteroids, and antivirals reduced mortality while diuretics, antibiotics, and antidiabetics increased it. Confounding makes some results very unreliable. For example, diuretics like furosemide are often used to treat fluid overload, which is more likely in ICU or advanced disease requiring aggressive fluid resuscitation. Hospitalization length has increased risk of significant confounding, for example longer hospitalization increases the chance of receiving a medication, and death may result in shorter hospitalization. Mortality results may be more reliable. Confounding by indication is likely to be significant for many medications. Authors adjustments have very limited severity information (admission type refers to ward vs. ER department on initial arrival). We can estimate the impact of confounding from typical usage..
Dec 2023, Frontiers in Public Health, https://www.frontiersin.org/articles/10.3389/fpubh.2023.1280434/full, https://c19p.org/mehrizi
184. Charif et al., Predictive Factors of Death and the Clinical Profile of Hospitalized Covid-19 Patients in Morocco: A One-Year Mixed Cohort Study
615 patient HCQ late treatment study: 27% lower mortality (p=0.0005).Retrospective 615 hospitalized COVID-19 patients in Morocco, showing lower mortality with HCQ in unadjusted results.
Dec 2022, Cureus, https://www.cureus.com/articles/122896-predictive-factors-of-death-and-the-clinical-profile-of-hospitalized-covid-19-patients-in-morocco-a-one-year-mixed-cohort-study, https://c19p.org/charif
185. Azaña Gómez et al., Mortality risk factors in patients with SARS-CoV-2 infection and atrial fibrillation: Data from the SEMI-COVID-19 registry
1,799 patient HCQ late treatment study: 36% lower mortality (p<0.0001).Retrospective 1,816 COVID-19 patients with atrial fibrillation in Spain, showing lower mortality with HCQ treatment.
Mar 2022, Medicina Clínica, https://www.sciencedirect.com/science/article/pii/S0025775322000549, https://c19p.org/azanagomez
186. Rubio-Sánchez et al., Prognostic factors for the severity of SARS-CoV-2 infection
197 patient HCQ late treatment study: 40% lower severe cases (p=0.02).Retrospective 197 hospitalized COVID-19 patients in Spain, showing lower progression to pneumonia with HCQ in unadjusted results.
Mar 2021, Advances in Laboratory Medicine / Avances en Medicina de Laboratorio, https://www.degruyter.com/document/doi/10.1515/almed-2021-0017/html, https://c19p.org/rubiosanchez
187. Dey et al., Hydroxy Chloroquine Prophylaxis Experience in Doctor Community with COVID-19 in West Bengal
117 patient HCQ prophylaxis study: 92% lower mortality (p=0.09), 27% fewer moderate/severe cases (p=0.39), and 16% lower hospitalization (p=0.55).Retrospective 117 COVID-19 positive doctors in India showing lower mortality and severity with HCQ prophylaxis, without statistical significance in unadjusted results without group details. Results do not include the risk of positive cases.
Jun 2024, J. College of Medical Sciences-Nepal, https://www.nepjol.info/index.php/JCMSN/article/view/43302, https://c19p.org/dey2
188. Patel et al., Factors Associated with COVID-19 Breakthrough Infection in the Pre-Omicron Era Among Vaccinated Patients with Rheumatic Diseases: A Cohort Study
11,468 patient HCQ prophylaxis study: 46% fewer cases (p=0.001).Retrospective 11,468 vaccinated rheumatic disease patients in the USA, showing lower risk of COVID-19 with HCQ/CQ use compared with all other treatments. Adjusted results are only provided with respect to specific other treatments.
Jul 2022, medRxiv, https://www.medrxiv.org/content/10.1101/2022.07.13.22277606, https://c19p.org/patel4
189. Hernandez-Cardenas et al., Hydroxychloroquine for the treatment of severe respiratory infection by COVID-19: a randomized controlled trial
214 patient HCQ late treatment RCT: 12% lower mortality (p=0.66).Very late stage RCT with 214 patients, mean SpO2 65%, 162 on mechanical ventilation, showing no significant difference in mortality. Patients not intubated at baseline show greater improvement, HR 0.43 [0.09-2.03]. Table 4 shows different results to the abstract - table 4 adjusted HR 0.80 [0.51-1.23], abstract HR 0.88 [0.51-1.53]. There was no significant difference in severe adverse events.
Feb 2021, medRxiv, https://www.medrxiv.org/content/10.1101/2021.02.01.21250371v1, https://c19p.org/hernandezcardenas
190. Bernaola et al., Observational Study of the Efficiency of Treatments in Patients Hospitalized with Covid-19 in Madrid
1,645 patient HCQ late treatment study: 17% lower mortality (p<0.0001).HCQ HR 0.83 [0.77-0.89] based on propensity score matched retrospective analysis of 1,645 hospitalized patients. Prednisone HR 0.85 [0.82-0.88], 14 other medications showed either no signicant benefit or a negative effect.
Jul 2020, medRxiv, https://www.medrxiv.org/content/10.1101/2020.07.17.20155960v1, https://c19p.org/bernaola
191. Salesi et al., Clinical signs, symptoms, and severity of COVID-19 in patients with rheumatic diseases during the COVID-19 epidemic
77 patient HCQ prophylaxis study: 85% lower severe cases (p=0.003) and 18% fewer moderate/severe cases (p=0.35).Retrospective study of 77 outpatients with rheumatic diseases diagnosed with COVID-19, showing lower risk of severe COVID-19 with HCQ use in unadjusted results.
Dec 2023, Immunopathologia Persa, https://immunopathol.com/Article/ipp-40568, https://c19p.org/salesi
192. Liu et al., Factors affecting different COVID-19 outcomes in patients with systemic lupus erythematosus during the second pandemic wave of COVID-19 in China
301 patient HCQ prophylaxis study: 39% lower severe cases (p=0.26).Retrospective 301 consecutive SLE patients with COVID-19, showing lower risk of severe outcomes with HCQ use, with statistical significance in multivariable adjusted model 1 but not model 2.
Feb 2024, Lupus, http://journals.sagepub.com/doi/10.1177/09612033241230736, https://c19p.org/liu18
193. Huang et al., Effect of traditional therapeutics on prevalence and clinical outcomes of coronavirus disease 2019 in Chinese patients with autoimmune diseases
432 patient HCQ prophylaxis study: 43% lower hospitalization (p=0.09) and 6% more cases (p=0.25).Retrospective 432 autoimmune disease patients in China showing lower hospitalization with HCQ without statistical significance (OR 0.566, p=0.085) in unadjusted results, slightly higher COVID-19 cases without statistical significance, and increased cough compared with CNI.
Dec 2023, J. Translational Autoimmunity, https://www.sciencedirect.com/science/article/pii/S2589909023000400, https://c19p.org/huang7
194. Rabe et al., Impact of SARS-CoV-2 infection on patients with systemic lupus erythematosus in England prior to vaccination: a retrospective observational cohort study
6,145 patient HCQ prophylaxis study: 29% fewer cases (p=0.22).Retrospective cohort of 6,145 SLE patients showing lower incidence of COVID-19 for patients receiving HCQ/CQ (antimalarials), without statistical significance. Groups were not matched and results may be influenced by factors such as disease severity. HCQ/antimalarials were used more in moderate/severe SLE patients, suggesting that the estimated protective effect will underestimate the real effect.
Nov 2023, BMJ Open, https://bmjopen.bmj.com/lookup/doi/10.1136/bmjopen-2022-071072, https://c19p.org/rabe
195. Dulcey et al., Long-Term Hydroxychloroquine and Its Association with Covid-19 Infection, a Cohort Study from a South American Hospital
967 patient HCQ prophylaxis study: 21% fewer cases (p=0.27).PSM retrospective 322 rheumatological patients on HCQ and 645 matched controls, showing lower risk of COVID-19 with treatment, without statistical significance. Authors mention lower mortality with HCQ but do not provide details. Only an abstract is available.
May 2023, J. Clinical Rheumatology, https://journals.lww.com/10.1097/RHU.0000000000001986, https://c19p.org/dulcey
196. Sukumar et al., The Frontline War: A Case-control study of risk factors for COVID-19 among health care workers
116 patient HCQ prophylaxis study: 38% fewer cases (p=0.3).Case control study of healthcare workers in India, showing lower risk of cases with HCQ prophylaxis, without statistical significance. While authors comment negatively, as may be required for publication, and this study alone is not statistically significant, the result is consistent with the positive results in all studies to date.
Nov 2022, F1000Research, https://f1000research.com/articles/11-1298/v1, https://c19p.org/sukumar
197. Becetti et al., Prevalence of coronavirus disease 2019 in a multiethnic cohort of patients with autoimmune rheumatic diseases in Qatar
700 patient HCQ prophylaxis study: 37% fewer cases (p=0.17).Retrospective 700 patients with autoimmune rheumatic disease in Qatar, showing lower risk of COVID-19 with HCQ use, without statistical significance. For patients having close contact with COVID-19 cases, there was a statistically significant association with HCQ use and lower risk of COVID-19 in unadjusted results.
Aug 2022, Qatar Medical J., https://www.qscience.com/content/journals/10.5339/qmj.2022.37, https://c19p.org/becetti
215 patient HCQ ICU study: 29% lower mortality (p=0.07).
Retrospective 215 mechanically ventilated COVID-19 patients in Brazil, 71 treated with HCQ, showing lower mortality with treatment in unadjusted results, without statistical significance. Authors note HCQ was used more toward the start of the pandemic, which may introduce confounding due to overall protocols improving over time, suggesting that the actual benefit may be greater.
Jun 2022, The J. Critical Care Medicine, https://www.sciendo.com/article/10.2478/jccm-2022-0015, https://c19p.org/osawa
199. Guglielmetti et al., Treatment for COVID-19—a cohort study from Northern Italy
600 patient HCQ late treatment study: 28% lower mortality (p=0.1).Retrospective 600 hospitalized patients in Italy, showing lower mortality with HCQ treatment, without reaching statistical significance (p = 0.1).
Oct 2021, Scientific Reports, https://www.nature.com/articles/s41598-021-00243-4/, https://c19p.org/guglielmetti2
200. Darcis et al., Long-term clinical follow-up of patients suffering from moderate-to-severe COVID-19 infection: a monocentric prospective observational cohort study
199 patient HCQ late treatment study: 32% lower PASC (p=0.58).Prospective observational study of 199 hospitalized COVID-19 patients in Belgium showing a high prevalence of persistent symptoms including dyspnea and fatigue at 6 months after discharge. Pulmonary function tests revealed reduced diffusion capacity, and CT scans showed a high prevalence of persistent lung abnormalities at 3 months, mainly ground glass opacities. Logistic regression shows lower risk of persistent symptoms with HCQ treatment, without statistical significance.
Aug 2021, Int. J. Infectious Diseases, https://www.sciencedirect.com/science/article/pii/S1201971221005725, https://c19p.org/darcis
201. Bae et al., Recent Hydroxychloroquine Use Is Not Significantly Associated with Positive PCR Results for SARS-CoV-2: A Nationwide Observational Study in South Korea
3,441 patient HCQ prophylaxis PSM study: 30% fewer cases (p=0.18).Retrospective database analysis of prior HCQ usage in South Korea, showing non-statistically significantly lower mortality and cases with treatment.
Feb 2021, Viruses 2021, https://www.mdpi.com/1999-4915/13/2/329, https://c19p.org/bae
203. Jung et al., Effect of hydroxychloroquine pre-exposure on infection with SARS-CoV-2 in rheumatic disease patients: A population-based cohort study
2,066 patient HCQ prophylaxis study: 59% lower mortality (p=1) and 13% more cases (p=0.86).Retrospective cohort study of RA and SLE patients not showing a significant difference in PCR+ cases. PCR+ does not distinguish asymptomatic cases or severity. There was only one death which was in the control group. No other information on severity is provided. 33% of the control group used HCQ within the last year. Remaining confounding by differences in the nature and severity of rheumatic disease is likely.
Dec 2020, Clinical Microbiology and Infection, https://www.sciencedirect.com/science/article/pii/S1198743X20307527, https://c19p.org/jung
204. Guglielmetti et al., Severe COVID-19 pneumonia in Piacenza, Italy – a cohort study of the first pandemic wave
218 patient HCQ late treatment study: 35% lower mortality (p=0.22).Retrospective 218 hospitalized patients in Italy showing non-statistically significant 35% lower mortality with HCQ, hazard ratio aHR 0.65 [0.33–1.30].
Dec 2020, J. Infection and Public Health, https://www.sciencedirect.com/science/article/pii/S1876034120307516, https://c19p.org/guglielmetti
205. Lambermont et al., Predictors of Mortality and Effect of Drug Therapies in Mechanically Ventilated Patients With Coronavirus Disease 2019: A Multicenter Cohort Study
247 patient HCQ late treatment study: 32% lower mortality (p=0.46).Retrospective 247 mechanically ventilated patients showing lower mortality with HCQ, but not statistically significant on multiple Cox regression. The paper gives the p value for multiple Cox (0.46) and simple Cox (0.02), but does not specify the adjusted risk values.
Nov 2020, Critical Care Explorations, https://journals.lww.com/ccejournal/Fulltext/2020/12000/Predictors_of_Mortality_and_Effect_of_Drug.10.aspx, https://c19p.org/lambermont
206. Rodriguez-Gonzalez et al., COVID-19 in hospitalized patients in Spain: a cohort study in Madrid
1,208 patient HCQ late treatment study: 23% lower mortality (p=0.26).Retrospective 1255 patients in Spain showing lower mortality with HCQ. Subject to confounding by indication.
Nov 2020, Int. J. Antimicrobial Agents, https://www.sciencedirect.com/science/article/pii/S0924857920304696, https://c19p.org/rodriguezgonzalez
207. Revollo et al., Hydroxychloroquine pre-exposure prophylaxis for COVID-19 in healthcare workers
487 patient HCQ prophylaxis PSM study: 23% fewer cases (p=0.52).Retrospective PrEP analysis with 69 healthcare workers on PrEP HCQ, and 418 control. Authors report PCR and IgG results, with no baseline results for either. Authors note they "identified 69 HCWs receiving HCQ" while providing no information as to why or when they started HCQ. No conclusions can be drawn from this study because many workers may have been positive before starting HCQ. Only 14% of workers chose to use HCQ and they may have been motivated to do so because they had an infection. Authors perform several different adjustments, finding very different results. No information on death, hospitalization, symptoms, or severity is provided. Details on timing of serology and baseline serology status is not provided. Potential bias due to self-selection for risk. 25% of infections were detected before 7 days, indicating that they actually happened earlier (PCR false positive is very high initially). It is likely that many infections were before HCQ could reach therapeutic..
Nov 2020, J. Antimicrobial Chemotherapy, https://academic.oup.com/jac/advance-article/doi/10.1093/jac/dkaa477/5997449, https://c19p.org/revollo
208. Datta et al., No Role of HCQ in COVID-19 Prophylaxis: A Survey amongst Indian Doctors
281 patient HCQ prophylaxis study: 22% fewer cases (p=0.47).Survey of Indian doctors not finding a significant effect of HCQ prophylaxis.
Nov 2020, J. Vaccines & Vaccination, S6:1000002, https://www.longdom.org/open-access/no-role-of-hcq-in-covid19-prophylaxis-a-survey-amongst-indian-doctors.pdf, https://c19p.org/datta
209. Behera et al., Role of ivermectin in the prevention of SARS-CoV-2 infection among healthcare workers in India: A matched case-control study
372 patient HCQ prophylaxis study: 28% fewer cases (p=0.29).Retrospective matched case-control prophylaxis study for HCQ, ivermectin, and vitamin C with 372 healthcare workers, showing lower COVID-19 incidence for all treatments, with statistical significance reached for ivermectin. HCQ OR 0.56, p = 0.29 Ivermectin OR 0.27, p < 0.001 Vitamin C OR 0.82, p = 0.58
Nov 2020, PLOS ONE, https://journals.plos.org/plosone/article?id=10.1371/journal.pone.0247163, https://c19p.org/behera
210. Ñamendys-Silva et al., Outcomes of patients with COVID-19 in the Intensive Care Unit in Mexico: A multicenter observational study
164 patient HCQ ICU study: 32% lower mortality (p=0.19).Retrospective 164 ICU patients in Mexico showing 32% lower mortality with HCQ+AZ and 37% lower with CQ. HCQ+AZ vs. neither HCQ or CQ relative risk RR 0.68, p = 0.03 CQ vs. neither HCQ or CQ relative risk RR 0.63, p = 0.02 HCQ+AZ or CQ vs. neither relative risk RR 0.65, p = 0.006
Oct 2020, Heart & Lung, https://www.sciencedirect.com/science/article/pii/S014795632030412X, https://c19p.org/namendyssilva
607 patient HCQ late treatment study: 20% lower mortality (p=0.36).
Retrospective 607 patients reporting results for early outpatient HCQ use with mortality odds ratio OR 0.092 [0.022-0.381], p = 0.001 (65 patients), and for hospital use, mortality odds ratio OR 0.737 [0.38-1.41], p = 0.36 (558 patients). Median age 69.
Oct 2020, eClinicalMedicine, https://www.sciencedirect.com/science/article/pii/S2589537020303357, https://c19p.org/guisadovasco
212. Piñana et al., Risk factors and outcome of COVID-19 in patients with hematological malignancies
HCQ prophylaxis study: 36% lower mortality (p=0.11).Retrospective study of 367 hematology patients with COVID-19 in Spain. Among 216 patients with very severe COVID-19, there was significantly lower mortality with azithromycin treatment. Mortality was also lower with HCQ, but without statistical significance.
Aug 2020, Experimental Hematology & Oncology, https://ehoonline.biomedcentral.com/articles/10.1186/s40164-020-00177-z, https://c19p.org/pinana
213. D'Arminio Monforte et al., Effectiveness of Hydroxychloroquine in COVID-19 disease: A done and dusted situation?
539 patient HCQ late treatment study: 34% lower mortality (p=0.12).Retrospective 539 COVID-19 hospitalized patients in Milan, with treatment a median of 1 day after admission, showing lower mortality with HCQ and with HCQ+AZ, with statistical significance only for HCQ+AZ.
Jul 2020, Int. J. Infectious Diseases, https://www.ijidonline.com/article/S1201-9712(20)30600-7/fulltext, https://c19p.org/darminiomonforte
214. Luo et al., Metformin Treatment Was Associated with Decreased Mortality in COVID-19 Patients with Diabetes in a Retrospective Analysis
283 patient HCQ late treatment study: 32% lower mortality (p=0.72).Retrospective 283 COVID-19+ diabetes patients in China, showing non-statistically significant lower mortality with HCQ/CQ treatment.
May 2020, The American J. Tropical Medicine and Hygiene, https://www.ajtmh.org/configurable/content/journals$002ftpmd$002f103$002f1$002farticle-p69.xml?t:ac=journals%24002ftpmd%24002f103%24002f1%24002farticle-p69.xml, https://c19p.org/luo3h
215. Capsoni et al., CPAP Treatment In COVID-19 Patients: A Retrospective Observational Study In The Emergency Department
52 patient HCQ late treatment study: 40% lower ventilation (p=0.3).Small 52 patient retrospective study of patients with acute respiratory failure showing lower rates of intubation with HCQ.
Nov 2020, Research Square, https://www.researchsquare.com/article/rs-113418/v1, https://c19p.org/capsoni
70 patient HCQ prophylaxis study: 50% lower mortality (p=0.67).
Retrospective hospitalized rheumatic disease patients showing 50% lower mortality for patients on HCQ.
Oct 2020, medRxiv, https://www.medrxiv.org/content/10.1101/2020.10.26.20219154v1, https://c19p.org/arleo
217. Smith et al., Observational Study on 255 Mechanically Ventilated Covid Patients at the Beginning of the USA Pandemic
255 patient HCQ late treatment study: 27% lower mortality (p=0.002).Retrospective 255 mechanical ventilation patients in USA, showing that weight-adjusted HCQ+AZ improved survival by over 100%. QTc prolongation did not correlate with cumulative HCQ dose or HCQ serum level. Although authors mention immortal time bias, full details on the timing of HCQ administration is not provided and this is not fully addressed. Survival curves indicate immortal time bias will significantly change results, although the observed benefit appears to exceed the potential bias.
May 2021, medRxiv, https://www.medrxiv.org/content/10.1101/2021.05.28.21258012v1, https://c19p.org/smith
218. Ashraf et al., COVID-19 in Iran, a comprehensive investigation from exposure to treatment outcomes
100 patient HCQ early treatment study: 68% lower mortality (p=0.15).Small limited trial with 100 patients concluding that HCQ improved clinical outcome, OR 0.016 [0.002-0.11] in regression analysis.
Apr 2020, medRxiv doi:10.1101/2020.04.20.20072421, https://www.researchgate.net/publication/341197843_COVID-19_in_Iran_a_comprehensive_investigation_from_exposure_to_treatment_outcomes, https://c19p.org/ashraf
219. Lecronier et al., Comparison of hydroxychloroquine, lopinavir/ritonavir, and standard of care in critically ill patients with SARS-CoV-2 pneumonia: an opportunistic retrospective analysis
80 patient HCQ ICU study: 42% lower mortality (p=0.24), 6% lower treatment escalation (p=0.73), and 15% improved viral clearance (p=0.61).Retrospective 80 ICU patients, 22 SOC, 20 lopinavir/ritonavir, 38 HCQ. 28 day mortality 24% (HCQ) versus 41% (SOC), a 41% decrease, but not statistically significant due to very small sample sizes. No statistically significant differences found for treatment escalation, ventilator-free days, viral load, or mortality. Authors consider treatment escalation more important than mortality, for unknown reasons.
Jul 2020, Critical Care, 2020, https://ccforum.biomedcentral.com/articles/10.1186/s13054-020-03117-9, https://c19p.org/lecronier
220. Assad et al., Pharmacotherapy prescribing pattern and outcome for hospitalized patients with severe and critical COVID-19
291 patient HCQ late treatment study: 60% lower mortality (p=0.002).Retrospective 346 hospitalized patients in Iraq, showing lower mortality with HCQ in unadjusted results. HCQ results are only provided within the 93% of patients treated with enoxaparin.
Oct 2022, Current Issues in Pharmacy and Medical Sciences, https://www.sciendo.com/article/10.2478/cipms-2022-0020, https://c19p.org/assad
221. Samajdar et al., Ivermectin and Hydroxychloroquine for Chemo-Prophylaxis of COVID-19: A Questionnaire Survey of Perception and Prescribing Practice of Physicians vis-a-vis Outcomes
309 patient HCQ prophylaxis study: 75% fewer cases (p<0.0001).Physician survey in India with 164 ivermectin prophylaxis, 129 HCQ prophylaxis, and 81 control patients, showing significantly lower COVID-19 cases with treatment. Details of the treatment and control groups and the definition of cases are not provided, and the results are subject to survey bias. Authors also report on community prophylaxis but present only combined ivermectin/HCQ results.
Nov 2021, J. the Association of Physicians India, https://www.researchgate.net/publication/356294136_Ivermectin_and_Hydroxychloroquine_for_Chemo-Prophylaxis_of_COVID-19_A_Questionnaire_Survey_of_Perception_and_Prescribing_Practice_of_Physicians_vis-a-vis_Outcomes, https://c19p.org/samajdarh
222. Núñez-Gil et al., Mortality risk assessment in Spain and Italy, insights of the HOPE COVID-19 registry
954 patient HCQ late treatment study: 8% lower mortality (p=0.005).Retrospective database study of 1,021 patients in Ecuador, Germany, Italy, and Spain, showing HCQ propensity score adjusted mortality odds ratio aOR 0.88, p=0.005.
Nov 2020, Internal and Emergency Medicine, https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7649104/, https://c19p.org/nunezgil
223. Maldonado et al., COVID-19 incidence and outcomes in a home dialysis unit in Madrid (Spain) at the height of the pandemic
12 patient HCQ late treatment study: 91% lower mortality (p=0.17).Very small retrospective of 12 dialysis patients showing 1/11 deaths with HCQ and 1/1 without HCQ.
Nov 2020, Nefrología, https://www.sciencedirect.com/science/article/pii/S0211699520301661, https://c19p.org/maldonado
224. Niwas et al., Clinical outcome, viral response and safety profile of chloroquine in COVID-19 patients — initial experience
29 patient HCQ late treatment study: 29% faster recovery (p=0.008).Retrospective 12 hospitalized patients in India treated with CQ and 17 controls, showing faster recovery with treatment. There was no significant difference in viral clearance. The CQ group mean age was 41.3 vs. 47.6 for controls.
Oct 2020, Advances in Respiratory Medicine, https://journals.viamedica.pl/advances_in_respiratory_medicine/article/view/69692, https://c19p.org/niwas
225. Abella et al., Efficacy and Safety of Hydroxychloroquine vs Placebo for Pre-exposure SARS-CoV-2 Prophylaxis Among Health Care Workers
125 patient HCQ prophylaxis RCT: 5% fewer cases (p=1).Very small early-terminated underpowered PrEP RCT with 64/61 HCQ/control patients and only 8 infections, HCQ infection rate 6.3% versus control 6.6%, RR 0.95 [0.25 - 3.64]. There was no hospitalization or death, no significant difference in QTc, no severe adverse events, no cardiac events (e.g., syncope and arrhythmias) observed. Medication adherence was 81%. Therapeutic levels of HCQ may not have been reached by the time of the infection in the first week. 2 infections were reported to be after discontinuation of the medication, but the authors do not specify which arm these were in. Hypothetically, if these were both in the HCQ arm, the resulting RR for treatment would be much lower.
Sep 2020, JAMA Internal Medicine, https://jamanetwork.com/journals/jamainternalmedicine/fullarticle/2771265, https://c19p.org/abella
226. Alamdari et al., Mortality Risk Factors among Hospitalized COVID-19 Patients in a Major Referral Center in Iran
459 patient HCQ late treatment study: 55% lower mortality (p=0.03).Retrospective 459 patients in Iran with 93% treated with HCQ, showing HCQ mortality RR 0.45, p = 0.028. HCQ was the only antiviral that showed a significant difference. There was relatively few control patients and the result is subject to confounding by indication. Average admission delay 5.72 days.
Sep 2020, The Tohoku J. Experimental Medicine, https://www.jstage.jst.go.jp/article/tjem/252/1/252_73/_article/-char/ja/, https://c19p.org/alamdari
227. Santos et al., Determinants of COVID-19 disease severity in patients with underlying rheumatic disease
38 patient HCQ prophylaxis study: 92% lower mortality (p=0.19).Prospective study of 38 hospitalized rheumatic disease patients with COVID-19 in Spain, showing no mortality with existing HCQ use compared to 32% without, not reaching statistical significance. Authors also report on the use of HCQ/CQ after hospitalization. The prophylaxis and late treatment results are listed separately [Santos, Santos].
Jul 2020, Clinical Rheumatology, https://link.springer.com/10.1007/s10067-020-05301-2, https://c19p.org/santos
228. Cavalcanti et al., Hydroxychloroquine with or without Azithromycin in Mild-to-Moderate Covid-19
667 patient HCQ late treatment RCT: 16% lower mortality (p=0.77) and 28% higher hospitalization (p=0.3).Late stage RCT of 667 hospitalized patients with up to 14 days of symptoms at enrollment and receiving up to 4 liters per minute supplemental oxygen, not finding a significant effect after 15 days. Authors note: "the trial cannot definitively rule out either a substantial benefit of the trial drugs or a substantial harm", sample sizes are too small. The paper uses the terms mild and moderate, however all patients had serious enough disease to be hospitalized, and 14% were actually randomized in the ICU. The trial had significant protocol deviations and unusually low medication adherence. Randomization resulted in 64.3% male patients (HCQ) vs. 54.2% (control) which may significantly affect results due to the much higher risk for male patients. Authors note: "our aim was to exclude patients already receiving longer and potentially therapeutic doses of the study treatments" in explanation for why the study protocol was changed to exclude patients with previous use of..
Jul 2020, NEJM, https://www.nejm.org/doi/full/10.1056/NEJMoa2019014, https://c19p.org/cavalcanti
229. Boulware et al., A Randomized Trial of Hydroxychloroquine as Postexposure Prophylaxis for Covid-19
821 patient HCQ prophylaxis RCT: 17% fewer cases (p=0.35).Remote post-exposure prophylaxis RCT reporting that "[HCQ] did not prevent illness compatible with Covid-19 or confirmed infection when used as postexposure prophylaxis within 4 days after exposure". However, this statement is incorrect - cases were reduced, just without statistical significance - it's not possible to conclude there was no efficacy. Additionally, treatment was not within 4 days - there was up to 68 hours shipping delay as below. Further, 6 independent analyses of the data in this study indicate efficacy: [arxiv.org, blog.philbirnbaum.com, drive.google.com, longdom.org, medrxiv.org, osf.io, researchgate.net]. COVID-19 cases were reduced by [49%, 29%, 16%] respectively when taken within ~[70, 94, 118] hours of exposure (including shipping delay). The treatment delay-response relationship is significant at p=0.002. For more detailed analysis, see [c19hcq.org]. See also: [nejm.org]. Authors compare with treatment with folic acid. [Kaur] et al. note that folic..
Jun 2020, NEJM, June 3 2020, https://www.nejm.org/doi/full/10.1056/NEJMoa2016638, https://c19p.org/boulwarepep
30 patient HCQ late treatment PSM study: 25% faster recovery (p=0.45), 13% longer hospitalization (p=0.75), and no change in viral clearance (p=0.99).
Retrospective 25 hospitalized patients treated with cephalosporin, azithromycin, and HCQ, and 217 SOC patients in South Korea, reporting no significant differences. 5 patients receiving lopinavir/ritonavir and HCQ >5 days were excluded for unknown reasons. HCQ was typically initiated based on progression or side effects from another treatment. Conflicting results are reported. Table 2 indicates 15 CA/HCQ patients after matching, while Table S2 shows 25, and the Table 3 count is blank. S2 appears to incorrectly show before matching results, and the after matching results are missing in Table 3. 200mg HCQ bid.
May 2022, PLOS ONE, https://journals.plos.org/plosone/article?id=10.1371/journal.pone.0267645, https://c19p.org/hong2
231. Rutskaya-Moroshan et al., Clinical Characteristics, Prognostic Factors, and Outcomes of COVID-19 in Autoimmune Rheumatic Disease Patients: A Retrospective Case–Control Study from Astana, Kazakhstan
140 patient HCQ prophylaxis study: 38% lower severe cases (p=1) and 24% lower hospitalization (p=1).Retrospective case-control study of 140 COVID-19 patients with autoimmune rheumatic diseases (AIRDs) and 140 matched controls showing higher rates of hospitalization, oxygen therapy, and mechanical ventilation with AIRDs. For the AIRD patients, there was no significant difference in outcomes based on HCQ use (only 10 patients).
Aug 2024, Medicina, https://www.mdpi.com/1648-9144/60/9/1377, https://c19p.org/rutskayamoroshan
232. Bassets-Bosch et al., Negativización de PCR a SARS-CoV-2 en muestra respiratoria en pacientes con necesidad de asistencia recurrente
15 patient HCQ late treatment study: 29% faster viral clearance (p=0.45).Retrospective 15 pediatric patients in Spain, showing faster viral clearance with HCQ+AZ, without statistical significance. Treatment time and details are not provided.
Apr 2022, Anales de Pediatría, https://www.sciencedirect.com/science/article/pii/S1695403321000126, https://c19p.org/bassetsbosch
233. Rangel et al., Chronic Hydroxychloroquine Therapy and COVID-19 Outcomes: A Retrospective Case-Control Analysis
153 patient HCQ prophylaxis study: 25% lower mortality (p=0.77) and 22% lower hospitalization (p=0.29).Retrospective 50 COVID-19 patients that take chronic HCQ, compared to a matched sample of patients not taking chronic HCQ, showing lower mortality and ICU admission, and shorter hospitalization for HCQ patients, but not statistically significant due to the small number of events. The actual benefit for HCQ could be much larger. The study does not address the risk of being sick enough to visit the hospital. HCQ users are likely systemic autoimmune disease patients and authors do not adjust for the very different baseline risk for these patients. Other research shows that the risk of COVID-19 for systemic autoimmune disease patients is much higher overall, Ferri et al. show OR 4.42, p<0.001 [Ferri].
Jan 2021, J. the American Academy of Dermatology, https://www.sciencedirect.com/science/article/pii/S0190962221001109, https://c19p.org/rangel
234. Synolaki et al., The Activin/Follistatin-axis is severely deregulated in COVID-19 and independently associated with in-hospital mortality
312 patient HCQ late treatment study: 24% lower mortality (p=0.27).Retrospective 117 patients showing lower mortality for HCQ patients, without statistical significance. Version 1 of this paper stated: "HCQ, AZ, [and ...] were found to be independently associated with survival when treatment commenced at FACTCLINYCoD scores <3". FACTCLINYCoD scores predict mortality risk based on severity markers and comorbidities.
Sep 2020, medRxiv, https://www.medrxiv.org/content/10.1101/2020.09.05.20184655v2, https://c19p.org/synolaki
235. Gonzalez et al., The Prognostic Value of Eosinophil Recovery in COVID-19: A Multicentre, Retrospective Cohort Study on Patients Hospitalised in Spanish Hospitals
9,644 patient HCQ late treatment study: 27% lower mortality (p=0.06).Retrospective study focused on eosinophil recovery with 9,644 hospitalized patients in Spain, showing lower mortality for HCQ (14.7% vs 29.2%, p<0.001), and AZ (15.3% vs. 18.4%, p<0.001). With a multivariate model including potential confounding factors, HCQ and AZ are associated with lower mortality, HCQ OR 0.662, p=0.057.
Aug 2020, medRxiv, https://www.medrxiv.org/content/10.1101/2020.08.18.20172874v1, https://c19p.org/gonzalez2
236. Trullàs et al., High in-hospital mortality due to COVID-19 in a community hospital in Spain: a prospective observational study
100 patient HCQ late treatment study: 36% lower mortality (p=0.12).Retrospective 100 hospitalized patients in Spain showing lower mortality with HCQ+AZ.
Jul 2020, Research Square, https://www.researchsquare.com/article/rs-39421/v1, https://c19p.org/trullas
237. Kim et al., One-year mortality and associated factors in older hospitalized COVID-19 survivors: a Nationwide Cohort Study in Korea
63,369 patient HCQ late treatment study: 15% lower mortality (p=0.62).Retrospective 63,369 hospitalized COVID-19 survivors aged 60 years or older in Korea, showing lower 1-year mortality with macrolides (including azithromycin), higher 1-year mortality with corticosteroids (including dexamethasone and methylprednisolone), and no significant difference with HCQ (only used for 0.2% of patients).
Oct 2024, Scientific Reports, https://www.nature.com/articles/s41598-024-76871-3, https://c19p.org/kim21h
238. Klebanov et al., Antimalarials are not Effective as Pre-Exposure Prophylaxis for COVID-19: A Retrospective Matched Control Study
62,069 patient HCQ prophylaxis study: 31% lower mortality (p=0.8) and 6% more cases (p=0.7).Retrospective 3,074 patients with antimalarial prescriptions and 58,955 matched controls, showing no significant differences with antimalarial prophylaxis for PCR+ cases (99% HCQ). Authors provide only PCR+ and mortality outcomes, and do not provide intermediate clinical outcomes that may show a statistically significant benefit. Authors do not adjust for the very different baseline risk for systemic autoimmune disease patients. Other research shows that the risk of COVID-19 for systemic autoimmune disease patients is much higher overall, Ferri et al. show OR 4.42, p<0.001 [Ferri] (for symptomatic disease).
Jun 2023, J. Drugs in Dermatology, https://jddonline.com/articles/dermatology/S1545961623P0840X, https://c19p.org/klebanov
239. Cárdenas-Jaén et al., Gastrointestinal symptoms and complications in patients hospitalized due to COVID-19, an international multicentre prospective cohort study (TIVURON project)
829 patient HCQ late treatment study: 56% lower severe cases (p=0.13).Retrospective 829 hospitalized COVID-19 patients in Spain focused on gastrointestinal symptoms, showing lower risk of severe COVID-19 with HCQ treatment in bivariate analysis, without statistical significance.
Jun 2023, Gastroenterología y Hepatología, https://www.sciencedirect.com/science/article/pii/S2444382423001104, https://c19p.org/cardenasjaen
240. Hafez et al., Antiviral Used among Non-Severe COVID-19 Cases in Relation to Time till Viral Clearance: A Retrospective Cohort Study
1,486 patient HCQ late treatment study: 12% faster viral clearance (p=0.59).Retrospective hospitalized patients in the United Arab Emirates, showing no significant difference in viral clearance with different combinations of HCQ, AZ, favipiravir, and lopinavir/ritonavir.
Apr 2022, Antibiotics, https://www.mdpi.com/2079-6382/11/4/498, https://c19p.org/hafez
241. Beaumont et al., Factors associated with hospital admission and adverse outcome for COVID-19: role of social factors and medical care
296 patient HCQ late treatment study: 14% lower combined mortality/intubation (p=0.55).Retrospective 296 hospitalized patients in France, showing no significant difference with HCQ treatment.
Feb 2022, Infectious Diseases Now, https://www.sciencedirect.com/science/article/pii/S266699192200032X, https://c19p.org/beaumont
242. Uygen et al., Effect of Hydroxychloroquine Use on the Length Of Hospital Stay in Children Diagnosed With Covid 19
40 patient HCQ late treatment study: 12% faster viral clearance (p=0.05).Retrospective 40 pediatric hospitalized patients, 15 treated with HCQ, showing 7.2 vs. 8.2 days until PCR-, not quite reaching statistical significance.
Sep 2021, Northern Clinics of Istanbul, https://northclinist.com/jvi.aspx?pdir=nci&plng=eng&un=NCI-65471&look4=, https://c19p.org/uygen
243. Gönenli et al., Analysis of the Prophylactic use of Hydroxychloroquine at the Beginning of the COVID-19 Pandemic Among Physicians
564 patient HCQ prophylaxis study: 30% lower progression (p=0.77) and 19% more cases (p=0.58).Small prophylaxis survey showing lower, but not statistically significant, progression to pneumonia (3 of 148 HCQ, 12 of 416 control), RR 0.70, p = 0.77. There was a higher incidence of cases with HCQ, OR 1.19, p = 0.58, which may be due to survey bias, treatment self-selection, and inconsistent regimens. Improvement on severity may be related to the higher HCQ concentration in lung tissue, and also reflect that binary PCR does not distinguish replication-competence. Details of the pneumonia numbers for treatment/control are from the author, it's unclear why the lower progression to pneumonia was not reported in the paper.
Dec 2020, Infectious Diseases and Clinical Microbiology, https://www.idcmjournal.org/hqn-use-among-physicians-during-the-pandemic, https://c19p.org/gonenli
244. Orioli et al., Clinical characteristics and short-term prognosis of in-patients with diabetes and COVID-19: A retrospective study from an academic center in Belgium
73 patient HCQ late treatment study: 13% lower mortality (p=1).Small retrospective study of 73 diabetic patients in Belgium, 55 HCQ patients, showing HCQ RR 0.87, p = 1.0.
Dec 2020, Diabetes & Metabolic Syndrome: Clinical Research & Reviews, https://www.sciencedirect.com/science/article/pii/S1871402120305154, https://c19p.org/orioli
245. Peng et al., Early versus late acute kidney injury among patients with COVID-19—a multicenter study from Wuhan, China
4,020 patient HCQ late treatment study: 11% lower progression (p=0.63).Retrospective 4020 hospitalized patients in China showing non-statistically significant lower risk of acute kidney injury with HCQ.
Dec 2020, Nephrology Dialysis Transplantation, https://academic.oup.com/ndt/article/35/12/2095/6020340, https://c19p.org/peng
246. Rodriguez et al., Severe infection due to the SARS-CoV-2 coronavirus: Experience of a tertiary hospital with COVID-19 patients during the 2020 pandemic
43 patient HCQ late treatment study: 59% lower mortality (p=0.23).Small prospective study of 43 hospitalized patients with 39 taking HCQ, showing unadjusted mortality relative risk RR 0.41, p=0.23.
Nov 2020, Medicina Intensiva, https://www.sciencedirect.com/science/article/pii/S2173572720301739, https://c19p.org/rodriguez
247. Rivera-Izquierdo et al., Agentes terapéuticos utilizados en 238 pacientes hospitalizados por COVID-19 y su relación con la mortalidad
238 patient HCQ late treatment study: 19% lower mortality (p=0.75).Retrospective 238 hospitalized patients in Spain showing lower mortality with HCQ, adjusted hazard ratio aHR 0.81 [0.24-2.76].
Jul 2020, Medicina Clínica, https://www.sciencedirect.com/science/article/pii/S0025775320304486, https://c19p.org/riveraizquierdo
248. Paccoud et al., Compassionate use of hydroxychloroquine in clinical practice for patients with mild to severe Covid-19 in a French university hospital
89 patient HCQ late treatment study: 11% lower mortality (p=0.88).Retrospective of 89 hospitalized patients, survival HR 0.89 [0.23-3.47], not statistically significant. Authors note that unmeasured confounders may have persisted and the study may be underpowered.
Jun 2020, Clinical Infectious Diseases, https://academic.oup.com/cid/article/doi/10.1093/cid/ciaa791/5859555, https://c19p.org/paccoud
249. Hraiech et al., Lack of viral clearance by the combination of hydroxychloroquine and azithromycin or lopinavir and ritonavir in SARS-CoV-2-related acute respiratory distress syndrome
32 patient HCQ ICU study: 65% lower mortality (p=0.21) and 3% worse viral clearance (p=1).Retrospective 45 ICU patients, 17 treated with HCQ+AZ, showing no significant difference in viral clearance after 6 days, or mortality 6 days from ARDS.
May 2020, Ann. Intensive Care, https://annalsofintensivecare.springeropen.com/articles/10.1186/s13613-020-00678-4, https://c19p.org/hraiech
250. Magagnoli et al., Outcomes of hydroxychloroquine usage in United States veterans hospitalized with Covid-19
807 patient HCQ late treatment study: 11% lower mortality (p=0.74).Retrospective 807 hospitalized patients, no statistically significant reduction in mortality or the need for mechanical ventilation with HCQ or HCQ+AZ, or for death with HCQ+AZ, HR 1.83, p=0.009 for HCQ mortality. The preprint notes that HCQ was more likely to be prescribed to patients with more severe disease, however this was deleted in the published version. 425 patients had dispositions of death or discharge by the end of the study period and thus did not encounter the issue of length-biased sampling and differential rates of right-censored observations among the groups. Also see: [mediterranee-infection.com]
Apr 2020, Med, https://www.sciencedirect.com/science/article/pii/S2666634020300064, https://c19p.org/magagnoli
251. Yegerov et al., Epidemiological and Clinical Characteristics, and Virologic Features of COVID-19 Patients in Kazakhstan: a Nation-Wide, Retrospective, Cohort Study
1,072 patient HCQ late treatment study: 95% lower mortality (p=1).Retrospective 1,072 hospitalized patients in Kazakhstan showing no mortality for HCQ treated patients, however only 23 patients received treatment - this result is not statistically significant.
Jan 2021, medRxiv, https://www.medrxiv.org/content/10.1101/2021.01.06.20249091v1, https://c19p.org/yegerov
252. Soto-Becerra et al., Real-World Effectiveness of hydroxychloroquine, azithromycin, and ivermectin among hospitalized COVID-19 patients: Results of a target trial emulation using observational data from a nationwide Healthcare System in Peru
3,322 patient HCQ late treatment study: 18% lower mortality (p<0.0001).Retrospective database study of 5683 patients, 692 received HCQ/CQ+AZ, 200 received HCQ/CQ, 203 received ivermectin, 1600 received AZ, 358 received ivermectin+AZ, and 2630 received standard of care. This study includes anyone with ICD-10 COVID-19 codes which includes asymptomatic PCR+ patients, therefore many patients in the control group are likely asymptomatic with regards to SARS-CoV-2, but in the hospital for another reason. For those that had symptomatic COVID-19, there is also likely significant confounding by indication. In this study all medications show higher mortality at day 30, which is consistent with asymptomatic (for COVID-19) or mild condition patients being more common in the control group. For ivermectin they show 30 day mortality aHR = 1.39 [0.88 - 2.22]. KM curves show that the treatment groups were in more serious condition, and also that after about day 35 survival became better with ivermectin. The last day available for ivermectin shows RR 0.83, p = 0.01. More..
Oct 2020, medRxiv, https://www.medrxiv.org/content/10.1101/2020.10.06.20208066v1, https://c19p.org/sotobecerra
253. Shoaibi et al., Comparative Effectiveness of Famotidine in Hospitalized COVID-19 Patients
29,451 patient HCQ late treatment study: 15% lower mortality (p=0.001).Retrospective database analysis focused on famotidine but also showing results for HCQ users, with unadjusted mortality RR 0.85, p<0.001 (13.6% vs. 16.1%).
Sep 2020, medRxiv, https://www.medrxiv.org/content/10.1101/2020.09.23.20199463v1, https://c19p.org/shoaibi
254. Fung et al., Effect of common maintenance drugs on the risk and severity of COVID-19 in elderly patients
HCQ prophylaxis study: 13% lower mortality (p=0.15), 3% lower hospitalization (p=0.63), and 9% fewer cases (p=0.02).Retrospective database analysis of 374,229 patients in the USA, showing no significant difference with HCQ use, however authors do not adjust for the very different baseline risk for systemic autoimmune disease patients. Other research shows that the risk of COVID-19 for systemic autoimmune disease patients is much higher overall, Ferri et al. show OR 4.42, p<0.001 [Ferri]. Authors compare with patients that never used HCQ and with patients that previously used HCQ. The comparison with patients previously using HCQ is more relevant because the matching of patients with systemic autoimmune disease is likely to be better.
Sep 2021, PLoS ONE, https://journals.plos.org/plosone/article?id=10.1371/journal.pone.0266922, https://c19p.org/fung
255. de Gonzalo-Calvo et al., A blood microRNA classifier for the prediction of ICU mortality in COVID-19 patients: a multicenter validation study
491 patient HCQ ICU study: 38% lower mortality (p=0.23).Retrospective 491 ICU patients in Spain showing lower mortality with HCQ without statistical significance in unadjusted results.
Jun 2023, Respiratory Research, https://respiratory-research.biomedcentral.com/articles/10.1186/s12931-023-02462-x, https://c19p.org/degonzalocalvo
256. Fernández-Cruz et al., Higher mortality of hospitalized haematologic patients with COVID-19 compared to non-haematologic is driven by thrombotic complications and development of ARDS: An age-matched cohorts study
71 patient HCQ late treatment study: 27% lower mortality (p=0.47).Retrospective 71 hospitalized haematologic patients in Spain, showing lower mortality with HCQ treatment in unadjusted results and without statistical significance.
Jan 2022, Clinical Infection in Practice, https://www.sciencedirect.com/science/article/pii/S259017022200005X, https://c19p.org/fernandezcruz
257. Menardi et al., A retrospective analysis on pharmacological approaches to COVID-19 patients in an Italian hub hospital during the early phase of the pandemic
277 patient HCQ late treatment study: 35% lower mortality (p=0.12).Retrospective 277 hospitalized patients in Italy, showing lower mortality with HCQ treatment, not reaching statistical significance, and subject to confounding by indication.
Sep 2021, PharmAdvances, http://www.pharmadvances.com/a-retrospective-analysis-on-pharmacological-approaches-to-covid-19-patients-in-an-italian-hub-hospital-during-the-early-phase-of-the-pandemic-2/, https://c19p.org/menardi
258. Mahto et al., Seroprevalence of IgG against SARS-CoV-2 and its determinants among healthcare workers of a COVID-19 dedicated hospital of India
689 patient HCQ prophylaxis study: 27% lower IgG positivity (p=0.38).Retrospective 689 healthcare workers in India, showing no significant difference in IgG positivity with HCQ prophylaxis in unadjusted results.
Feb 2021, American J. Blood Research, https://www.ncbi.nlm.nih.gov/labs/pmc/articles/PMC8010601/, https://c19p.org/mahto
259. Mahale et al., A Retrospective Observational Study of Hypoxic COVID-19 Patients Treated with Immunomodulatory Drugs in a Tertiary Care Hospital
134 patient HCQ late treatment study: 29% lower mortality (p=0.36).Retrospective 134 hospitalized COVID-19 patients in India, showing no significant difference with HCQ treatment in unadjusted results.
Dec 2020, Indian J. Critical Care Medicine, https://www.ijccm.org/doi/pdf/10.5005/jp-journals-10071-23599, https://c19p.org/mahaleh
260. Chari et al., Clinical features associated with COVID-19 outcome in multiple myeloma: first results from the International Myeloma Society data set
502 patient HCQ late treatment study: 33% lower mortality (p=0.17).Retrospective multiple myeloma patients showing lower mortality with HCQ treatment, unadjusted RR 0.67, p = 0.17 (data is in the supplementary material).
Dec 2020, Blood, https://www.sciencedirect.com/science/article/pii/S0006497120839044, https://c19p.org/chari
261. Bielza et al., Clinical characteristics, frailty and mortality of residents with COVID-19 in nursing homes of a region of Madrid
630 patient HCQ late treatment study: 22% lower mortality (p=0.09).Retrospective 630 elderly patients in Spain showing lower mortality with HCQ treatment, unadjusted relative risk RR 0.78, p = 0.09. HCQ was used more often with patients that were hospitalized (24% versus 3% use in the nursing homes). Median age 87.
Dec 2020, J. the American Medical Directors Association, https://www.sciencedirect.com/science/article/pii/S1525861020310525, https://c19p.org/bielza
262. Qin et al., Low molecular weight heparin and 28-day mortality among patients with coronavirus disease 2019: A cohort study in the early epidemic era
749 patient HCQ late treatment study: 34% lower mortality (p=0.61).Low molecular weight heparin study also showing results for HCQ treatment, unadjusted HCQ mortality relative risk RR 0.66, p = 0.61.
Nov 2020, Thrombosis Research, https://www.sciencedirect.com/science/article/pii/S0049384820306277, https://c19p.org/qin
263. Santos et al., Determinants of COVID-19 disease severity in patients with underlying rheumatic disease
38 patient HCQ late treatment study: 26% lower mortality (p=0.6).Prospective study of 38 hospitalized rheumatic disease patients with COVID-19 in Spain, showing no mortality with existing HCQ use compared to 32% without, not reaching statistical significance. Authors also report on the use of HCQ/CQ after hospitalization. The prophylaxis and late treatment results are listed separately [Santos, Santos].
Jul 2020, Clinical Rheumatology, https://link.springer.com/10.1007/s10067-020-05301-2, https://c19p.org/santos2
264. Krishnan et al., Clinical comorbidities, characteristics, and outcomes of mechanically ventilated patients in the State of Michigan with SARS-CoV-2 pneumonia
152 patient HCQ late treatment study: 20% lower mortality (p=0.48).Retrospective 152 mechanically ventilated patients in the USA showing unadjusted lower mortality with vitamin C, vitamin D, HCQ, and zinc treatment, statistically significant only for vitamin C.
Jul 2020, J. Clinical Anesthesia, https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7369577/, https://c19p.org/krishnan
265. Martinez-Lopez et al., Multiple Myeloma and SARS-CoV-2 Infection: Clinical Characteristics and Prognostic Factors of Inpatient Mortality
167 patient HCQ late treatment study: 33% lower mortality (p=0.2).Retrospective 167 multiple myeloma patients in Spain, showing no significant difference in mortality with HCQ treatment in unadjusted results without group details.
Jun 2020, Blood Cancer J., https://www.nature.com/articles/s41408-020-00372-5, https://c19p.org/martinezlopez
266. Goldman et al., Remdesivir for 5 or 10 Days in Patients with Severe Covid-19
397 patient HCQ late treatment study: 22% lower mortality (p=0.46).Study focused on remdesivir but with results for HCQ in the supplementary appendix, showing 9% death with HCQ versus 12% control, unadjusted relative risk uRR 0.78, p = 0.46.
May 2020, NEJM, https://www.nejm.org/doi/10.1056/NEJMoa2015301, https://c19p.org/goldmanh
267. Martin-Vicente et al., Absent or insufficient anti-SARS-CoV-2 S antibodies at ICU admission are associated to higher viral loads in plasma, antigenemia and mortality in COVID-19 patients
92 patient HCQ ICU study: 59% lower mortality (p=0.41).Retrospective 92 ICU patients with almost all treated with HCQ and only one non-HCQ treated patient that died, showing unadjusted non-statistically significant lower mortality with treatment.
Mar 2021, medRxiv, https://www.medrxiv.org/content/10.1101/2021.03.08.21253121v1, https://c19p.org/martinvicente
268. Alqassieh et al., Clinical characteristics and predictors of the duration of hospital stay in COVID-19 patients in Jordan
131 patient HCQ late treatment study: 18% shorter hospitalization (p=0.11).Prospective observational study of 131 COVID-19 patients in Jordan, showing 18% shorter hospital stay with HCQ, p = 0.11.
Dec 2020, F1000Research, https://f1000research.com/articles/9-1439, https://c19p.org/alqassieh
269. Desbois et al., Prevalence and clinical features of COVID-19 in a large cohort of 199 patients with sarcoidosis
199 patient HCQ prophylaxis study: 17% fewer cases (p=1).Retrospective 199 sarcoidosis patients showing non-statistically significant HCQ RR 0.83, p=1.0.
Jul 2020, Research Square, https://www.researchsquare.com/article/rs-41653/v1, https://c19p.org/desbois
270. Shabrawishi et al., Negative nasopharyngeal SARS-CoV-2 PCR conversion in response to different therapeutic interventions
93 patient HCQ late treatment study: 15% improved viral clearance (p=0.66).Retrospective 93 hospitalized patients in Saudi Arabia showing a non-statistically significant 15% reduction in PCR positive results at day 5, RR 0.85, p = 0.65. The treatment group had significantly more severe illness and significantly more male patients.
May 2020, medRxix, https://www.medrxiv.org/content/10.1101/2020.05.08.20095679v1, https://c19p.org/shabrawishi
271. Chen et al., A pilot study of hydroxychloroquine in treatment of patients with common coronavirus disease-19 (COVID-19)
30 patient HCQ late treatment RCT: 29% lower progression (p=0.57) and 100% worse viral clearance (p=1).30 moderate hospitalized cases, all recovered. Time to RNA negative comparable. Less frequent radiological progression with HCQ but not statistically significant. One HCQ patient developed to a severe case. Treatment group 4 years older and with higher incidence of hypertension.
Mar 2020, J. Zhejiang University, https://pubmed.ncbi.nlm.nih.gov/32391667/, https://c19p.org/chenmedsci
272. Sarhan et al., Efficacy of the early treatment with tocilizumab-hydroxychloroquine and tocilizumab-remdesivir in severe COVID-19 Patients
108 patient HCQ late treatment RCT: 26% lower mortality (p=0.39), 26% higher hospital discharge (p=0.39), and 25% longer hospitalization (p=0.06).Small 108 patient RCT comparing HCQ vs. remdesivir in very late stage treatment. All patients received tocilizumab. There were significant unadjusted baseline differences in ventilation and ICU admission. NCT04779047. REC-H-PhBSU-21011.
Nov 2021, J. Infection and Public Health, https://www.sciencedirect.com/science/article/pii/S1876034121003452, https://c19p.org/sarhan
273. Salvador et al., Clinical Features and Prognostic Factors of 245 Portuguese Patients Hospitalized With COVID-19
245 patient HCQ late treatment study: 33% lower mortality (p=0.1), 448% higher ventilation (p=0.003), and 17% lower combined mortality/intubation (p=0.21).Prospective study of 245 hospitalized patients, 121 treated with HCQ, showing lower (non-statistically significant) mortality and higher ventilation at 30 days. Confounding by indication is likely.
Mar 2021, Cureus, https://www.cureus.com/articles/53247-clinical-features-and-prognostic-factors-of-245-portuguese-patients-hospitalized-with-covid-19, https://c19p.org/salvador
274. Naseem et al., Predicting mortality in SARS-COV-2 (COVID-19) positive patients in the inpatient setting using a Novel Deep Neural Network
1,214 patient HCQ late treatment study: 33% lower mortality (p=0.34).Retrospective 1,214 hospitalized patients in Pakistan, 77 HCQ patients, showing 33% lower mortality with HCQ, multivariate Cox HR 0.67, p = 0.34.
Dec 2020, medRxiv, https://www.medrxiv.org/content/10.1101/2020.12.13.20247254v1, https://c19p.org/naseem
80 patient HCQ late treatment study: 17% lower mortality (p=0.5).
Retrospective 80 hospitalized severe COVID-19 patients in Turkey, showing no significant difference with HCQ treatment in unadjusted results. All patients received favipiravir.
Jul 2023, Acta Clinica Croatica, https://www.researchgate.net/publication/372951875_FACTORS_AFFECTING_PROGNOSIS_AND_MORTALITY_IN_SEVERE_COVID-19_PNEUMONIA_PATIENTS, https://c19p.org/afsin
276. Shukla et al., An observational multi-centric COVID-19 sequelae study among health care workers
679 patient HCQ prophylaxis study: 5% lower PASC (p=0.78).Retrospective 679 healthcare workers post COVID-19 discharge, 76 using HCQ prophylaxis, showing no significant difference in PASC.
Dec 2022, The Lancet Regional Health - Southeast Asia, https://www.sciencedirect.com/science/article/pii/S2772368222001469, https://c19p.org/shukla
277. Hall et al., Multi-institutional Analysis of 505 COVID-19 Patients Supported with ECMO: Predictors of Survival
505 patient HCQ ICU study: 11% lower mortality (p=0.31).Retrospective 505 ECMO patients showing no significant difference in mortality in unadjusted results.
Feb 2022, The Annals of Thoracic Surgery, https://www.sciencedirect.com/science/article/abs/pii/S0003497522001989, https://c19p.org/hall
278. Alwafi et al., Negative Nasopharyngeal SARS-CoV-2 PCR Conversion in Response to Different Therapeutic Interventions
93 patient HCQ late treatment study: 15% improved viral clearance (p=0.65).Retrospective 93 hospitalized patients in Saudi Arabia, 45 treated with CQ/HCQ, showing no significant difference in viral clearance. More patients treated with CQ/HCQ had severe cases at baseline (20% vs. 2%).
Jan 2022, Cureus, https://www.cureus.com/articles/82181-negative-nasopharyngeal-sars-cov-2-pcr-conversion-in-response-to-different-therapeutic-interventions, https://c19p.org/alwafi
279. Tu et al., Risk Factors for Severity and Mortality in Adult Patients Confirmed with COVID-19 in Sierra Leone: A Retrospective Study
180 patient HCQ late treatment study: 17% lower mortality (p=0.81).Retrospective 180 hospitalized COVID-19 patients in Sierra Leone, showing no significant difference with HCQ treatment in unadjusted results, however HCQ was significantly more likely to be used for severe patients (33% vs. 12%).
Jan 2022, Infectious Diseases & Immunity, https://journals.lww.com/10.1097/ID9.0000000000000037, https://c19p.org/tu
280. Turrini et al., Clinical Course and Risk Factors for In-Hospital Mortality of 205 Patients with SARS-CoV-2 Pneumonia in Como, Lombardy Region, Italy
205 patient HCQ late treatment study: 10% lower mortality (p=0.15).Retrospective 205 patients in Italy, 160 treated with HCQ, showing lower mortality with treatment in multivariate analysis, but not reaching statistical significance.
Jun 2021, Vaccines, https://www.mdpi.com/2076-393X/9/6/640, https://c19p.org/turrini
281. Haji Aghajani et al., Decreased in-hospital mortality associated with aspirin administration in hospitalized patients due to severe COVID-19
991 patient HCQ late treatment study: 19% lower mortality (p=0.09).Retrospective 991 hospitalized patients in Iran focusing on aspirin use but also showing results for HCQ, remdesivir, and favipiravir.
Apr 2021, J. Medical Virology, https://onlinelibrary.wiley.com/doi/10.1002/jmv.27053, https://c19p.org/hajiaghajani
282. Pham et al., Failure of chronic hydroxychloroquine in preventing severe complications of COVID-19 in patients with rheumatic diseases
42 patient HCQ prophylaxis study: 20% lower mortality (p=0.77) and 35% higher ICU admission (p=0.61).Tiny retrospective database analysis of hospitalized COVID-19 patients with rheumatologic disease containing 14 chronic HCQ and 28 control patients. Patients are very poorly matched. Bias against HCQ is clear in the abstract which mentions differences favoring HCQ but ignores those favoring control (large differences in ethnicity, rheumatic conditions, hypertension, coronary artery disease, solid organ transplant recipients, immunosuppresive drugs). 61% of control patients also received HCQ. Adherence for chronic HCQ patients was not examined. Despite the very large differences between the groups, no adjustments are made. The study claims that HCQ did not prevent severe cases, but the study is among hospitalized patients, i.e., they already have cases severe enough for hospitalization - this study can not identify a protective effect of HCQ that reduces the probability of disease severe enough for hospitalization.
Mar 2021, Rheumatology Advances in Practice, https://academic.oup.com/rheumap/advance-article/doi/10.1093/rap/rkab014/6156645, https://c19p.org/pham
283. Ubaldo et al., COVID-19: A Single-Center ICU Experience of the First Wave in the Philippines
31 patient HCQ ICU study: 18% lower mortality (p=0.64).Retrospective ICU patients in the Philippines showing unadjusted HCQ RR 0.82, p = 0.64.
Jan 2021, Critical Care Research and Practice, https://www.hindawi.com/journals/ccrp/2021/7510306/, https://c19p.org/ubaldo
79 patient HCQ late treatment study: 16% lower mortality (p=0.76).
Retrospective 79 hospitalized nonagenarian patients showing unadjusted HCQ mortality RR 0.84, p = 0.76.
Jan 2021, Revista Espanola de Quimioterapia, https://europepmc.org/article/med/33522213, https://c19p.org/roig
285. Khoubnasabjafari et al., Prevalence of COVID-19 in patients with rheumatoid arthritis (RA) already treated with hydroxychloroquine (HCQ) compared with HCQ-naive patients with RA: a multicentre cross-sectional study
1,858 patient HCQ prophylaxis study: 17% fewer cases (p=0.59).Survey analysis of 1,858 RA patients in Iran, showing no significant difference in cases with HCQ prophylaxis.
Jan 2021, Postgraduate Medical J., https://pmj.bmj.com/content/early/2021/01/13/postgradmedj-2020-139561, https://c19p.org/khoubnasabjafari
286. Tehrani et al., Risk factors for mortality in adult COVID-19 patients: frailty predicts fatal outcome in older patients
255 patient HCQ late treatment study: 13% lower mortality (p=0.63).Retrospective 255 hospitalized patients, 65 treated with HCQ, showing unadjusted RR 0.87, p=0.63. Confounding by indication is likely.
Oct 2020, Int. J. Infectious Diseases, https://www.sciencedirect.com/science/article/pii/S1201971220322761, https://c19p.org/tehrani
287. Pasquini et al., Effectiveness of remdesivir in patients with COVID-19 under mechanical ventilation in an Italian ICU
51 patient HCQ ICU study: 16% lower mortality (p=0.34).Retrospective 51 ICU patients under mechanical ventilation, 33 treated with HCQ, showing unadjusted lower mortality with treatment.
Aug 2020, J. Antimicrobial Chemotherapy, https://academic.oup.com/jac/article/75/11/3359/5896161, https://c19p.org/pasquini
288. Ip et al., Hydroxychloroquine and Tocilizumab Therapy in COVID-19 Patients - An Observational Study
2,512 patient HCQ late treatment study: 1% lower mortality (p=0.93).Retrospective study of late stage use on 2,512 hospitalized patients showing no significant differences in associated mortality for patients receiving any HCQ during the hospitalization (HR, 0.99 [95% CI, 0.80-1.22]), HCQ alone (HR, 1.02 [95% CI, 0.83-1.27]), or HCQ+AZ (HR, 0.98 [95% CI, 0.75-1.28]). Misclassification is possible due to manual abstraction of EHR data. They observed a change in the prescribing patterns of HCQ during the study timeframe. Confounding by indication.
May 2020, PLoS ONE, https://journals.plos.org/plosone/article?id=10.1371/journal.pone.0237693, https://c19p.org/ip2
289. Kamran et al., Clearing the fog: Is HCQ effective in reducing COVID-19 progression: A randomized controlled trial
500 patient HCQ late treatment study: 5% lower progression (p=1) and 26% improved viral clearance (p=0.001).Study of 349 low-risk hospitalized patients with 151 non-consenting or ineligible patients used as controls. SOC included zinc, vitamin C and vitamin D. A statistically significant improvement in PCR negativity is shown at day 7 with HCQ treatment, 52.1% (HCQ) versus 35.7% (control), p=0.001, but no statistically significant difference at day 14, or in progression. Patients were relatively young and there was no mortality. Only 3% of patients had any disease progression and all patients recovered, so there is little if any room for treatment benefit. Progression among higher-risk patients with comorbidities was lower with treatment (12.9% versus 28.6%, p=0.3, very few cases). Despite the title, this is not an RCT since patients self-selected the arm, or were chosen based on allergies/contraindications. The treatment group had about twice the number of patients with comorbidities. Treatment delay is unknown - it was recorded but not reported in the paper. Viral load was not measured...
Aug 2020, medRxiv, https://www.medrxiv.org/content/10.1101/2020.07.30.20165365v1, https://c19p.org/kamran
290. Azimi Pirsaraei et al., Anticoagulant Use in COVID-19 Patients: A Longitudinal Study From Zanjan, Iran
831 patient HCQ late treatment study: 39% lower mortality (p=0.16).Retrospective 831 hospitalized COVID-19 patients showing lower mortality with HCQ in unadjusted results, without statistical significance.
Aug 2024, Cureus, https://www.cureus.com/articles/263779-anticoagulant-use-in-covid-19-patients-a-longitudinal-study-from-zanjan-iran, https://c19p.org/azimipirsaraeih
291. Barra et al., COVID-19 in hospitalized patients in 4 hospitals in San Isidro, Buenos Aires, Argentina
668 patient HCQ late treatment study: 11% lower mortality (p=1).Retrospective 668 hospitalized patients in Argentina, 18 treated with HCQ, not showing a significant difference in unadjusted results.
Jul 2021, medRxiv, https://www.medrxiv.org/content/10.1101/2021.07.30.21261220v1, https://c19p.org/barra
292. An et al., Treatment Response to Hydroxychloroquine and Antibiotics for mild to moderate COVID-19: a retrospective cohort study from South Korea
226 patient HCQ late treatment study: 3% faster viral clearance (p=0.92).Retrospective of hospitalized patients with 31 HCQ patients and 195 standard treatment patients, not showing a significant difference in terms of viral clearance or recovery. There was no mortality in either group. "It is notable that HQ plus antibiotics group had worse baseline clinical profiles (i.e. higher percentage of moderate severity patients, more patients with fever >=37.5C, higher average body temperature) and prognostic indicators such as age, LDH, lymphocyte count, and CRP". We note that propensity score matching removed almost all of the male patients in the control group (40% -> 5%) but increased the percentage of male patients in the treatment group. This provides a large advantage to the control group because there is a very large difference in severity and mortality based on gender [ncbi.nlm.nih.gov]. In terms of viral RNA clearance we note that other research has found that "active viral replication drops quickly after the first week, and viable virus..
Jul 2020, medRxiv, https://www.medrxiv.org/content/10.1101/2020.07.04.20146548v1, https://c19p.org/an
293. Singh et al., Outcomes of Hydroxychloroquine Treatment Among Hospitalized COVID-19 Patients in the United States- Real-World Evidence From a Federated Electronic Medical Record Network
1,820 patient HCQ late treatment study: 5% lower mortality (p=0.72) and 19% lower ventilation (p=0.26).EHR analysis of 3,372 hospitalized COVID-19 patients not showing a significant difference for mortality or the risk of mechanical ventilation. Subject to the limitations of EHR analysis. Misclassification is possible. Confounding by indication is likely.
May 2020, medRxiv, https://www.medrxiv.org/content/10.1101/2020.05.12.20099028v1, https://c19p.org/singh
294. Macias et al., Similar incidence of Coronavirus Disease 2019 (COVID-19) in patients with rheumatic diseases with and without hydroxychloroquine therapy
722 patient HCQ prophylaxis study: 26% lower hospitalization (p=1) and 49% more cases (p=0.53).Very small retrospective study of rheumatic disease patients, sample size is too small for statistical significance (HCQ 0.5-4.0%, no-HCQ 0.4-2.7%). Confirmed cases were 1 HCQ and 2 no-HCQ, confirmed+likely cases were 1 HCQ and 3 no-HCQ. 1 HCQ and 2 no-HCQ patients were admitted to hospital. We do not think a conclusion can be drawn based on these sample sizes. There are very significant differences between the groups, for example 30% of the HCQ group have SLE vs. 2.5% of the no-HCQ group. SLE patients have a 5.7 times relative risk of pneumonia according to [ncbi.nlm.nih.gov], whereas the relative risk with glucocorticoids and TNF-α inhibitors is significantly lower [academic.oup.com]. Two more recent studies with rheumatic disease/autoimmune condition patients provide higher confidence.
May 2020, medRxiv, https://www.medrxiv.org/content/10.1101/2020.05.16.20104141v1, https://c19p.org/macias
295. Sbidian et al., Hydroxychloroquine with or without azithromycin and in-hospital mortality or discharge in patients hospitalized for COVID-19 infection: a cohort study of 4,642 in-patients in France
4,642 patient HCQ late treatment study: 5% higher mortality (p=0.74) and 20% higher hospital discharge (p=0.002).Retrospective of 4,642 hospitalized patients in France showing significantly faster discharge with HCQ and HCQ+AZ. No significant effect is seen on 28-day mortality, however many more control patients are still in hospital at 28 days. Other studies show faster resolution for HCQ, suggesting there will be a significant improvement when extending past 28 days. Hopefully authors will extend the analysis. Note that the median age is higher in the group not treated with HCQ or AZ. For other issues with the adjustments see [medrxiv.org]. Also see the analysis here [web.archive.org].
Jun 2020, medRxiv, https://www.medrxiv.org/content/10.1101/2020.06.16.20132597v1, https://c19p.org/sbidian
296. Karruli et al., Multidrug-Resistant Infections and Outcome of Critically Ill Patients with Coronavirus Disease 2019: A Single Center Experience
32 patient HCQ ICU study: 5% lower mortality (p=1).Retrospective 32 ICU patients, showing no significant difference with HCQ treatment in unadjusted results.
Aug 2021, Microbial Drug Resistance, https://www.liebertpub.com/doi/full-xml/10.1089/mdr.2020.0489, https://c19p.org/karrulih
297. Shabani et al., Evaluation of the Prophylactic Effect of Hydroxychloroquine on People in Close-Contact with Patients with Covid-19
113 patient HCQ prophylaxis study: 19% fewer symptomatic cases (p=1) and 6% more cases (p=1).Small PEP trial with 51 HCQ patients, not showing a significant difference in cases. IRCT20130917014693N10.
Aug 2021, Pulmonary Pharmacology & Therapeutics, https://www.sciencedirect.com/science/article/abs/pii/S109455392100081X, https://c19p.org/shabani
298. Roger et al., French Multicentre Observational Study on SARS-CoV-2 infections Intensive care initial management: the FRENCH CORONA Study
966 patient HCQ ICU study: no change in mortality (p=0.94).Prospective study of 966 ICU patients in France, 289 treated with HCQ, showing no significant difference with treatment. Time based confounding is likely because HCQ became increasingly controversial and less used over the time covered, while overall treatment protocols during this period improved dramatically, i.e., more control patients likely come later in the period when treatment protocols were greatly improved.
Jul 2021, Anaesthesia Critical Care & Pain Medicine, https://www.sciencedirect.com/science/article/pii/S2352556821001351, https://c19p.org/roger
299. Jacobs et al., Multi-institutional Analysis of 200 COVID-19 Patients treated with ECMO:Outcomes and Trends
200 patient HCQ late treatment study: 7% lower mortality (p=0.74).Prospective study of 200 ECMO patients showing no significant difference in unadjusted results for HCQ treatment. Time based confounding is likely because HCQ became increasingly controversial and less used over the time covered (as shown in figure 4), while overall treatment protocols during this period improved dramatically, i.e., more control patients likely come later in the period when treatment protocols were greatly improved.
Jul 2021, The Annals of Thoracic Surgery, https://www.sciencedirect.com/science/article/pii/S0003497521011772, https://c19p.org/jacobs
300. Çiyiltepe et al., The Effect of Pre-admission Hydroxychloroquine Treatment on COVID-19-Related Intensive Care Follow-up in Geriatric Patients
147 patient HCQ ICU study: 3% lower mortality (p=0.85).Retrospective 147 ICU patients in Turkey, showing no significant difference in outcomes based on HCQ treatment before ICU admission. This is not very informative, for example we do not know if HCQ treated patients were much less likely to be admitted to the ICU.
Apr 2021, South. Clin. Ist. Euras., https://jag.journalagent.com/scie/pdfs/SCIE-89847-RESEARCH_ARTICLE-CIYILTEPE.pdf, https://c19p.org/ciyiltep
301. Alegiani et al., Risk of COVID-19 hospitalization and mortality in rheumatic patients treated with hydroxychloroquine or other conventional DMARDs in Italy
HCQ prophylaxis study: 8% higher mortality (p=0.64) and 18% lower hospitalization (p=0.03).Retrospective database analysis case control study of rheumatic patients. When compared with other cDMARDs, HCQ users had significantly lower hospitalization, however there was no significant difference in mortality. Results differ significantly from previous studies, for example showing mortality OR 0.94 [0.83-1.06] for patients with rheumatic disease and mortality OR 0.88 [0.74-1.05] for patients with RA/SLE. Other research shows that the risk of COVID-19 for systemic autoimmune disease patients is much higher overall.
Apr 2021, Rheumatology, https://academic.oup.com/rheumatology/advance-article/doi/10.1093/rheumatology/keab348/6226505?searchresult=1, https://c19p.org/alegiani
302. Vernaz et al., Early experimental COVID-19 therapies: associations with length of hospital stay, mortality and related costs
198 patient HCQ late treatment PSM study: 15% lower mortality (p=0.71) and 49% longer hospitalization (p=0.002).Retrospective 840 hospitalized patients in Switzerland showing non-statistically significant lower mortality with HCQ but significantly longer hospitalization times. Confounding by indication is likely. PSM fails to adjust for severity with a 16% higher mNEWS score for HCQ vs. SOC in the matched cohort. Time varying confounding is likely. HCQ became controversial and was suspended towards the end of the period studied, therefore HCQ use was likely more frequent toward the beginning of the study period, a time when overall treatment protocols were significantly worse. Authors note: "overall, there was an indication bias, with the reason of prescription being associated with the outcome of interest. Indeed, patients with more severe COVID-19 were more likely to receive experimental therapies."
Dec 2020, Swiss Medical Weekly, https://smw.ch/article/doi/smw.2020.20446, https://c19p.org/vernaz
303. Annie et al., Hydroxychloroquine in hospitalized COVID-19 patients: Real world experience assessing mortality
734 patient HCQ late treatment study: 4% lower mortality (p=0.83).Retrospective database analysis with PSM not including COVID-19 severity, finding mortality OR 0.95 [0.62-1.46] for HCQ, and 1.24 [0.70-2.22] for HCQ+AZ. Confounding by indication likely.
Oct 2020, Pharmacotherapy, https://accpjournals.onlinelibrary.wiley.com/doi/10.1002/phar.2467, https://c19p.org/annie
304. Albani et al., Impact of Azithromycin and/or Hydroxychloroquine on Hospital Mortality in COVID-19
816 patient HCQ late treatment study: 18% lower mortality (p=0.15) and 9% higher ICU admission (p=0.7).Retrospective 1376 hospitalized patients in Italy, 211 treated with HCQ and 166 with HCQ+AZ.
Aug 2020, J, Clinical Medicine, https://www.mdpi.com/2077-0383/9/9/2800, https://c19p.org/albani
305. Salvarani et al., Susceptibility to COVID-19 in Patients Treated With Antimalarials: A Population-Based Study in Emilia-Romagna, Northern Italy
HCQ prophylaxis study: 6% fewer cases (p=0.75).Comparison of CQ/HCQ users with the general population in a region of Italy, showing no significant difference in the probability of COVID-19. CQ/HCQ users were mostly systemic autoimmune disease patients and authors do not adjust for the very different baseline risk for these patients. Other research shows that the risk of COVID-19 for systemic autoimmune disease patients is much higher overall, Ferri et al. show OR 4.42, p<0.001 [Ferri].
Aug 2020, Arthritis & Rheumatology, https://onlinelibrary.wiley.com/doi/10.1002/art.41475, https://c19p.org/salvarani
306. Gendebien et al., Systematic analysis of COVID-19 infection and symptoms in a systemic lupus erythematosus population: correlation with disease characteristics, hydroxychloroquine use and immunosuppressive treatments
225 patient HCQ prophylaxis study: 4% fewer cases (p=0.93).Small study of SLE patients taking HCQ with a phone survey for COVID-19 suggestive symptoms. There was 2 hospitalizations (group not identified) and no ICU or death cases. A similar percentage of suspected infections were reported for HCQ users and non-HCQ users, RR 0.96, p = 0.93. There was no mortality and severity was not analyzed to determine if HCQ treated patients fared better. No adjustment for concomitant medications or severity of SLE. Only 5 cases were PCR confirmed.
Jun 2020, Annals of the Rheumatic Diseases, https://ard.bmj.com/content/early/2020/06/25/annrheumdis-2020-218244, https://c19p.org/gendebien
307. Gianfrancesco et al., Characteristics associated with hospitalisation for COVID-19 in people with rheumatic disease: data from the COVID-19 Global Rheumatology Alliance physician-reported registry
600 patient HCQ prophylaxis study: 3% lower hospitalization (p=0.82).Analysis of rheumatic disease patients showing no significant association between antimalarial therapy and hospitalisation, OR=0.94 [0.57-1.57], p=0.82 after adjustments.
May 2020, Annals of the Rheumatic Diseases, 859-866, https://europepmc.org/article/med/32471903, https://c19p.org/gianfrancesco
308. Konig et al., Baseline use of hydroxychloroquine in systemic lupus erythematosus does not preclude SARS-CoV-2 infection and severe COVID-19
80 patient HCQ prophylaxis study: 3% lower hospitalization (p=0.88).Analysis of 80 SLE patients diagnosed with COVID-19, showing the frequency of hospitalisation did not differ between individuals using an antimalarial versus non-users (55% (16/29) vs 57% (29/51), p=ns. Authors suggest that the dosage used may be too low to reach therapeutic levels.
May 2020, Annals of the Rheumatic Diseases, https://ard.bmj.com/content/early/2020/05/20/annrheumdis-2020-217690, https://c19p.org/konig
309. Gendelman et al., Continuous Hydroxychloroquine or Colchicine Therapy Does Not Prevent Infection With SARS-CoV-2: Insights From a Large Healthcare Database Analysis
14,520 patient HCQ prophylaxis study: 8% fewer cases (p=0.88).Very small study of rheumatic disease/autoimmune disorder patients showing no significant difference but with only 3 chronic HCQ patient cases. Only considers people tested at a time when primarily symptomatic cases were tested. Other research shows that the risk of COVID-19 for systemic autoimmune disease patients is much higher overall, Ferri et al. show OR 4.42, p<0.001 [Ferri], which is the observed real-world risk, taking into account factors such as these patients potentially being more careful to avoid exposure. Adjusting for the difference in baseline risk using the result in Ferri et al. shows substantial benefit for HCQ, RR 0.211, but with only 3 HCQ cases the result is inconclusive. More recent studies with rheumatic disease/autoimmune condition patients provide higher confidence.
May 2020, Autoimmunity Reviews, July 2020, https://www.sciencedirect.com/science/article/pii/S1568997220301282, https://c19p.org/gendelman
310. Rao et al., Hydroxychloroquine as pre-exposure prophylaxis against COVID-19 infection among healthcare workers: a prospective cohort study
1,294 patient HCQ prophylaxis study: 11% fewer cases (p=0.68).Prospective PrEP study with low risk healthcare workers in India showing RR=0.89 [0.53-1.52]. There were no significant adverse effects. Only mean age and gender distribution are provided for baseline characteristics, no severity information is provided, and no adjustments were made. Authors analyze HCQ use for <8 vs. ≥8 weeks, noting a lack of statistical significance, but not providing the results.
Dec 2021, Expert Review of Anti-infective Therapy, https://www.tandfonline.com/doi/abs/10.1080/14787210.2022.2015326, https://c19p.org/rao
311. Cortez et al., Clinical characteristics and outcomes of COVID-19 patients in a tertiary hospital in Baguio City, Philippines
280 patient HCQ late treatment study: 15% lower mortality (p=1).Retrospective 280 hospitalized patients in the Philippines, 25 treated with HCQ, not showing any significant differences in unadjusted results.
Nov 2021, Western Pacific Surveillance and Response J., https://ojs.wpro.who.int/ojs/index.php/wpsar/article/view/852, https://c19p.org/cortez
312. Fitzgerald et al., Risk Factors for Infection and Health Impacts of the COVID-19 Pandemic in People with Autoimmune Diseases
4,666 patient HCQ prophylaxis study: 9% fewer cases (p=0.54).Retrospective 4666 people with autoimmune or inflammatory conditions, showing HCQ adjusted risk of COVID-19 OR 0.91 [0.68-1.23]. Results are not adjusted for the significantly different risk of COVID-19 depending on the type and severity of autoimmune or inflammatory condition.
Feb 2021, medRxiv, https://www.medrxiv.org/content/10.1101/2021.02.03.21251069v1, https://c19p.org/fitzgerald
313. Wang et al., Comorbidity and Sociodemographic determinants in COVID-19 Mortality in an US Urban Healthcare System
7,592 patient HCQ late treatment study: 6% lower mortality (p=0.63).Database analysis of 7,592 patients in NYC, showing adjusted HCQ mortality odds ratio OR 0.96, p = 0.82, and HCQ+AZ OR 0.94, p = 0.63
Jun 2020, medRxiv, https://www.medrxiv.org/content/10.1101/2020.06.11.20128926v1, https://c19p.org/wangrx
314. Lamback et al., Hydroxychloroquine with azithromycin in patients hospitalized for mild and moderate COVID-19
193 patient HCQ late treatment study: 9% lower mortality (p=0.83), 20% higher ICU admission (p=0.61), and 12% shorter hospitalization.Retrospective 193 hospitalized patients in Brazil not finding a significant difference with HCQ. The control group was composed of patients refusing HCQ or with contraindications. Time based confounding is very likely because HCQ became more controversial in Brazil over the time covered (Mar - Jun 2020), while overall treatment protocols during this period improved dramatically, i.e., more control patients (those refusing HCQ) likely come later in the period when treatment protocols were greatly improved. The paper does not mention the word "confounding" or make any adjustments.
Feb 2021, The Brazilian J. Infectious Diseases, https://www.sciencedirect.com/science/article/pii/S141386702100012X, https://c19p.org/lamback
315. Roy et al., Outcome of Different Therapeutic Interventions in Mild COVID-19 Patients in a Single OPD Clinic of West Bengal: A Retrospective study
29 patient HCQ early treatment study: 2% faster recovery (p=0.96).Retrospective database analysis of 56 mild COVID-19 patients, all treated with vitamin C, vitamin D, and zinc, comparing ivermectin + doxycycline (n=14), AZ (n=13), HCQ (n=14), and SOC (n=15), finding that all groups recover quickly, and there was no significant difference between the groups.
Mar 2021, medRxiv, https://www.medrxiv.org/content/10.1101/2021.03.08.21252883v1, https://c19p.org/royh
25 patient HCQ late treatment study: 38% improved viral clearance (p=0.17).
Early results from a very small trial, reported within the application for a later trial. Very minimal details are provided, but we include this as the earliest published results. For COVID-19 patients with pneumonia the viral negative conversion rate was 50% (5/10) with CQ versus 20% (3/15) with lopinavir/ritonavir.
Feb 2020, ChiCTR2000029741, http://www.chictr.org.cn/showproj.aspx?proj=49263, https://c19p.org/xia
317. Küçükakkaş et al., The effect of hydroxychloroquine against SARS-CoV-2 infection in rheumatoid arthritis patients
17 patient HCQ prophylaxis study: 43% higher ICU admission (p=1).Retrospective 17 rheumatoid arthritis COVID-19+ patients, 7 on HCQ treatment, showing no significant differences. They study reports only including hospitalized patients, but the results include non-hospitalized patients. Results do not reflect potential difference in the probability that a case is serious enough to have been tested and identified. Few group details are provided (even the age of patients in each group is not specified).
Jul 2021, Research Square, https://www.researchsquare.com/article/rs-43812/v1, https://c19p.org/kucukakkas
318. Salehi et al., Risk factors of death in mechanically ventilated COVID-19 patients: a retrospective multi-center study
125 patient HCQ ICU study: 14% higher mortality (p=0.44).Retrospective 125 mechanically ventilated ICU patients in Iran, showing no significant difference with HCQ treatment in unadjusted results.
Mar 2022, Research Square, https://www.researchsquare.com/article/rs-1362678/v1, https://c19p.org/salehih
319. Alhamlan et al., Epidemiology and Clinical Characteristics in Individuals with Confirmed SARS-CoV-2 Infection During the Early COVID-19 Pandemic in Saudi Arabia
HCQ late treatment study: 52% higher mortality (p=0.58).Retrospective hospitalized patients in Saudi Arabia showing higher mortality with most treatments although not reaching statistical significance. Confounding by indication, time, or other factors is likely (a 19x higher risk with lopinavir/ritonavir and 3.5x higher risk with azithromycin is not supported by other studies for example). The number of patients treated with HCQ is not provided.
Jul 2021, medRxiv, https://www.medrxiv.org/content/10.1101/2021.07.13.21260428v1, https://c19p.org/alhamlan
320. Sarfaraz et al., Determinants of in-hospital mortality in COVID-19; a prospective cohort study from Pakistan
186 patient HCQ late treatment study: 45% higher mortality (p=0.07).Retrospective 186 hospitalized patients in Pakistan showing unadjusted HCQ mortality RR 1.45, p = 0.07. Confounding by indication is likely.
Jan 2021, medRxiv, https://www.medrxiv.org/content/10.1101/2020.12.28.20248920v1, https://c19p.org/sarfaraz
321. Abdulrahman et al., The efficacy and safety of hydroxychloroquine in COVID19 patients : a multicenter national retrospective cohort
446 patient HCQ late treatment PSM study: 17% lower mortality (p=1) and 75% higher combined mortality/intubation (p=0.24).Retrospective analysis of acute care patients in Bahrain not showing a significant effect of HCQ. Confounding by indication is likely. Matching appears not to have matched for baseline severity. 17.5% of HCQ patients required oxygen while only 12.6% of control patients did.
Nov 2020, medRxiv, https://www.medrxiv.org/content/10.1101/2020.11.25.20234914v1, https://c19p.org/abdulrahman
299 patient HCQ late treatment RCT: 15% higher mortality (p=0.7) and 24% improved viral clearance (p=0.68).
Early terminated very late stage (95% on oxygen at baseline) DISCOVERY trial. 4% more patients were on ventilation at baseline in the HCQ group. This preprint presents more recent results than the earlier journal article.
Oct 2020, medRxiv, https://www.medrxiv.org/content/10.1101/2022.02.16.22271064, https://c19p.org/discovery
323. Shamsi et al., Survival and Mortality in Hospitalized Children with COVID-19: A Referral Center Experience in Yazd, Iran
183 patient HCQ late treatment study: 39% higher mortality (p=0.51).Retrospective 183 hospitalized pediatric COVID-19 patients in Iran, showing no significant difference in mortality with in unadjusted results.
Jul 2023, Canadian J. Infectious Diseases and Medical Microbiology, https://www.hindawi.com/journals/cjidmm/2023/5205188/, https://c19p.org/shamsih
324. Kamstrup et al., Hydroxychloroquine as a primary prophylactic agent against sars-cov-2 infection: a cohort study
60,334 patient HCQ prophylaxis study: 44% higher hospitalization (p=0.25) and 10% fewer cases (p=0.23).Retrospective HCQ users in Denmark, not showing a significant difference, however authors do not adjust for the very different baseline risk for systemic autoimmune disease patients. Authors appear unaware of research in the area, for example saying that "currently, no obvious connection exists between a known rheumatological disorder and the risk of contracting SARS-CoV-2". Many papers show that the risk of COVID-19 for systemic autoimmune disease patients is much higher overall, e.g., Ferri et al. show OR 4.42, p<0.001 [Ferri]. Supplementary data is not currently available.
May 2021, Int. J. Infectious Diseases, https://www.sciencedirect.com/science/article/pii/S1201971221004781, https://c19p.org/kamstrup
325. Solh et al., Clinical course and outcome of COVID-19 acute respiratory distress syndrome: data from a national repository
643 patient HCQ late treatment study: 18% higher mortality (p=0.17).Retrospective database analysis of 7,816 Veterans Affairs hospitalized patients analyzing progression to ARDS and 30-day mortality from ARDS. Confounding by indication is likely. Chronological bias is likely, with HCQ more likely to be used earlier on, before significant improvements in overall treatment. No results are provided for HCQ for progression to ARDS.
Oct 2020, medRxiv, https://www.medrxiv.org/content/10.1101/2020.10.16.20214130v1, https://c19p.org/solh
326. Saleemi et al., Time to negative PCR from symptom onset in COVID-19 patients on Hydroxychloroquine and Azithromycin - A real world experience
85 patient HCQ late treatment study: 21% slower viral clearance (p=0.05).Retrospective 65 HCQ+AZ, 20 control patients, showing median time to negative PCR of 23 days for HCQ+AZ vs. 19 days for control. Confounding by indication. 100% of non-HCQ group had mild disease vs. 63% of the HCQ+AZ group. More comorbidities and symptoms in the HCQ+AZ group.
Aug 2020, medRxiv, https://www.medrxiv.org/content/10.1101/2020.08.05.20151027v1, https://c19p.org/saleemi
327. Alosaimi et al., Analyzing the Difference in the Length of Stay (LOS) in Moderate to Severe COVID-19 Patients Receiving Hydroxychloroquine or Favipiravir
74 patient HCQ late treatment PSM study: 400% higher mortality (p=0.49), 43% shorter hospitalization (p=0.63), and 29% higher hospital discharge (p=0.74).Retrospective 200 hospitalized COVID-19 patients in Saudi Arabia, showing no significant difference in outcomes between HCQ and favipiravir.
Nov 2022, Pharmaceuticals, https://www.mdpi.com/1424-8247/15/12/1456, https://c19p.org/alosaimi
328. Lyashchenko et al., Systemic Exposure to Hydroxychloroquine and its relationship with outcome in severely ill COVID-19 patients in New York City
3,256 patient HCQ late treatment study: 48% higher mortality (p<0.0001).Retrospective very late stage hospitalized patients in New York during the first wave, showing no significant relationship between HCQ levels and outcomes. Authors note that the patients with data were the sickest patients.
Aug 2022, British J. Clinical Pharmacology, https://onlinelibrary.wiley.com/doi/10.1111/bcp.15489, https://c19p.org/lyashchenko
329. Malundo et al., Predictors of Mortality among inpatients with COVID-19 Infection in a Tertiary Referral Center in the Philippines
1,215 patient HCQ late treatment study: 24% higher mortality (p=0.32).Retrospective 1,215 hospitalized patients in the Phillipines, showing no significant difference in outcomes with remdesivir or HCQ use in unadjusted results subject to confounding by indication.
Jul 2022, IJID Regions, https://www.sciencedirect.com/science/article/pii/S2772707622000935, https://c19p.org/malundo
330. Soto et al., Mortality and associated risk factors in patients hospitalized due to COVID-19 in a Peruvian reference hospital
1,418 patient HCQ late treatment study: 6% higher mortality (p=0.46).Retrospective 1,418 very late stage (46% mortality) patients in Peru, showing no significant difference with HCQ. There is strong confounding by indication, for example 48% of patients with baseline SpO2 <70% were treated compared with 22% for SpO2 >95%. There may also be significant confounding by time with SOC changing substantially over the first few months of the pandemic.
Mar 2022, PLOS ONE, https://journals.plos.org/plosone/article?id=10.1371/journal.pone.0264789, https://c19p.org/sotoh
331. Albanghali et al., Clinical Characteristics and Treatment Outcomes of Mild to Moderate Covid-19 Patients in Saudi Arabia: A Single Centre Study
811 patient HCQ late treatment study: 35% higher mortality (p=0.46).Retrospective 811 hospitalized COVID+ patients in Saudi Arabia, showing higher mortality with HCQ treatment in unadjusted results subject to confounding by indication.
Feb 2022, J. Infection and Public Health, https://www.sciencedirect.com/science/article/pii/S187603412200034X, https://c19p.org/albanghali
332. Alghamdi et al., Clinical characteristics and treatment outcomes of severe (ICU) COVID-19 patients in Saudi Arabia: A single centre study
171 patient HCQ ICU study: 39% higher mortality (p=0.52).Retrospective 171 ICU patients in Saudi Arabia showing no significant difference for HCQ treatment in unadjusted results.
Aug 2021, Saudi Pharmaceutical J., https://www.sciencedirect.com/science/article/pii/S1319016421001559, https://c19p.org/alghamdi2
333. Gadhiya et al., Clinical characteristics of hospitalised patients with COVID-19 and the impact on mortality: a single-network, retrospective cohort study from Pennsylvania state
271 patient HCQ late treatment study: 5% higher mortality (p=0.89).Retrospective 283 patients in the USA showing higher mortality with all treatments (not statistically significant). Confounding by indication is likely. In the supplementary appendix, authors note that the treatments were usually given for patients that required oxygen therapy. Oxygen therapy and ICU admission (possibly, the paper includes ICU admission for model 2 in some places but not others) were the only variables indicating severity used in adjustments. Time based confounding is likely because HCQ became increasingly controversial and less used over the time covered (March 1 to May 31, 2020), while overall treatment protocols during this period improved dramatically, i.e., more control patients likely come later in the period when treatment protocols were greatly improved.
Apr 2021, BMJ Open, https://bmjopen.bmj.com/content/11/4/e042549.info, https://c19p.org/gadhiya
334. Mulhem et al., 3219 hospitalised patients with COVID-19 in Southeast Michigan: a retrospective case cohort study
3,219 patient HCQ late treatment study: 28% higher mortality (p=0.1).Retrospective database analysis of 3,219 hospitalized patients in the USA. Very different results in the time period analysis (Table S2), and results significantly different to other studies for the same medications (e.g., heparin OR 3.06 [2.44-3.83]) suggest significant confounding by indication and confounding by time.
Apr 2021, BMJ Open, https://bmjopen.bmj.com/content/11/4/e042042.info, https://c19p.org/mulhem
335. Alghamdi et al., Clinical Efficacy of Hydroxychloroquine in Patients with COVID-19: Findings from an Observational Comparative Study in Saudi Arabia
775 patient HCQ late treatment study: 7% higher mortality (p=0.88).Retrospective 775 hospitalized patients in Saudi Arabia showing no significant difference. There was no adjustment for severity or comorbidities. Confounding by indication is likely.
Mar 2021, Antibiotics, https://www.mdpi.com/2079-6382/10/4/365, https://c19p.org/alghamdi
336. Rosenthal et al., Risk Factors Associated With In-Hospital Mortality in a US National Sample of Patients With COVID-19
HCQ late treatment study: 8% higher mortality (p=0.13).Retrospective database analysis of 64,781 hospitalized patients in the USA, showing lower mortality with vitamin C or vitamin D (authors do not distinguish between the two), and higher mortality with zinc and HCQ, statistically significant for zinc. Authors excluded hospital-based outpatient visits, without explanation. Confounding by indication is likely, adjustments do not appear to include any information on COVID-19 severity at baseline.
Dec 2020, JAMA Network Open, https://jamanetwork.com/journals/jamanetworkopen/article-abstract/2773971, https://c19p.org/rosenthal
337. Aboulenain et al., The Effect of Hydroxychloroquine on In-Hospital Mortality in COVID-19
175 patient HCQ late treatment study: 15% higher mortality (p=0.72).Retrospective 175 hospitalized COVID-19 patients in the USA, showing no significant difference in mortality with HCQ. Authors note that "patients treated with HCQ in our cohort were more likely to be sicker at baseline".
Nov 2020, HCA Healthcare J. Medicine, https://scholarlycommons.hcahealthcare.com/hcahealthcarejournal/vol1/iss0/20, https://c19p.org/aboulenain
338. Rodriguez-Nava et al., Clinical characteristics and risk factors for mortality of hospitalized patients with COVID-19 in a community hospital: A retrospective cohort study
313 patient HCQ late treatment study: 6% higher mortality (p=0.77).Retrospective 313 patients, mostly critical stage and mostly requiring respiratory support, showing unadjusted RR 1.06, p = 0.77. Confounding by indication likely.
Nov 2020, Mayo Clinic Proceedings: Innovations, Quality & Outcomes, https://www.sciencedirect.com/science/article/pii/S2542454820302071, https://c19p.org/rodrigueznava
903 patient HCQ late treatment study: 37% higher mortality (p=0.28).
Convalescent plasma study also showing mortality based on HCQ treatment, unadjusted hazard ratio uHR 1.37, p = 0.28. Confounding by indication is likely.
Nov 2020, The American J. Pathology, https://www.sciencedirect.com/science/article/pii/S0002944020304892, https://c19p.org/salazar
1,402 patient HCQ late treatment study: 22% slower viral clearance (p=0.0001).
Health insurance database analysis failing to adjust for disease severity and not finding a significant difference in time to PCR- for LPV/r and HCQ. There are large differences in severity across groups. Authors did PSM but chose not to prioritize severity, resulting in incomparable groups, e.g., baseline pneumonia of 44% in the HCQ group and 15% in the control group (after PSM). Authors note this but offer no explanation for not correcting for severity: "However, the disease severity and proportion of accompanying pneumonia were still significantly higher in the LPV/r and HCQ-group".
Oct 2020, Int. J. Infectious Diseases, https://www.sciencedirect.com/science/article/pii/S1201971220322669, https://c19p.org/choi
194,637 patient HCQ prophylaxis study: 3% higher mortality (p=0.83).
Observational database study of RA/SLE patients in the UK, 194,637 RA/SLE patients with 30,569 having >= 2 HCQ prescriptions in the prior 6 months, HCQ HR 1.03 [0.80-1.33] (HR 0.78 before adjustments). 70 patients with HCQ prescriptions died. One major problem is that there is no knowlege of medication adherence for these 70 - for example, it is possible that they were part of the expected percentage of patients that did not take the medication as prescribed, invalidating the result. Other limitations include confounding by use of bDMARDs and confounding by severity of rheumatological disease.
Sep 2020, The Lancet Rheumatology, https://www.sciencedirect.com/science/article/pii/S2665991320303787, https://c19p.org/rentsch
342. Fried et al., Patient Characteristics and Outcomes of 11,721 Patients with COVID19 Hospitalized Across the United States
11,721 patient HCQ late treatment study: 27% higher mortality (p=0.001).Database analysis of 11,721 hospitalized patients, 4,232 on HCQ. Strong evidence for confounding by indication and compassionate use of HCQ. 24.9% of HCQ patients were on mechanical ventilation versus 12.2% control. Ventilation mortality was 70.5% versus 11.6%. This study does not adjust for the differences in comorbid conditions and disease severity, and therefore does not make a conclusion. Unadjusted HCQ mortality was 24.8% versus control 19.6%. Adjusting for ventilation only gives us 17.7% HCQ versus 19.6% control (adjusting the HCQ group to have the same proportion of ventilation patients), RR 0.90. Hopefully authors can do a full adjustment analysis. Comorbidities may favor control, while patients remaining in the hospital (5.3%) may favor HCQ (other studies show faster resolution for HCQ patients). Data inconsistencies have been found in this study, for example 99.4% of patients treated with HCQ were treated in urban hospitals, compared to 65% of untreated patients ..
Aug 2020, Clinical Infectious Disease, https://academic.oup.com/cid/advance-article/doi/10.1093/cid/ciaa1268/5898276, https://c19p.org/fried
343. Peters et al., Outcomes of Persons With COVID-19 in Hospitals With and Without Standard Treatment With (Hydroxy)chloroquine
1,949 patient HCQ late treatment study: 9% higher mortality (p=0.57).Retrospective study of HCQ use in 9 hospitals in the Netherlands, showing no significant difference in mortality with HCQ/CQ. Late stage (admitted to hospital with positive test or CT scan abnormalities). 4 of 7 hospitals started treatment only after further deterioration. Short cutoff (21 days) - other studies have shown treated patient cases resolved faster and more control patients remaining in hospital at this time. In the preprint, 58 of 341 control patients died. In the journal version, 53 of 353 control patients died. Significant differences between hospitals - HCQ hospitals had significantly older patients with significantly more comorbidities. Non-HCQ hospitals were "tertiary academic centres" whereas HCQ hospitals were "secondary care hospitals". Residual confounding likely. This study compares overcrowded regular hospitals with undercrowded academic hospitals. A subset of patients were excluded due to transfer to other hospitals. This introduces bias..
Aug 2020, Clinical Microbiology and Infection, https://www.clinicalmicrobiologyandinfection.com/article/S1198-743X(20)30615-7/fulltext, https://c19p.org/peters
344. Roomi et al., Efficacy of hydroxychloroquine and tocilizumab in patients with COVID-19: A single-center retrospective chart review
176 patient HCQ late treatment study: 38% higher mortality (p=0.54).Retrospective 176 hospitalized patients (144 HCQ, 32 control) showing no significant differences with HCQ or TCZ. Confounding by indication.
Aug 2020, J. Medical Internet Research, https://www.jmir.org/2020/9/e21758/, https://c19p.org/roomi
345. Singer et al., Hydroxychloroquine ineffective for COVID-19 prophylaxis in lupus and rheumatoid arthritis
32,758 patient HCQ prophylaxis study: 9% more cases (p=0.62).Comparison of the percentage of SLE/RA patients on immunosuppressants that were taking HCQ, for COVID-19 diagnosis versus other infections or outpatient visits, finding a similar percentage in each case. No mortality of severity information is provided to determine if HCQ treated patients fared better. No adjustment for concomitant medications or severity.
Aug 2020, Annals of the Rheumatic Diseases, https://ard.bmj.com/content/early/2020/08/19/annrheumdis-2020-218500, https://c19p.org/singer
346. Gupta et al., Factors Associated With Death in Critically Ill Patients With Coronavirus Disease 2019 in the US
2,215 patient HCQ late treatment study: 6% higher mortality (p=0.41).Analysis of 2,215 intensive care unit patients showing no significant differences with this very late stage use of HCQ.
Jul 2020, JAMA Intern. Med., https://jamanetwork.com/journals/jamainternalmedicine/fullarticle/2768602, https://c19p.org/gupta
347. Sosa-García et al., Experience in the management of severe COVID-19 patients in an intensive care unit
56 patient HCQ ICU study: 11% higher mortality (p=1).Small retrospective study of 56 ICU patients in Mexico showing HCQ RR 1.1, p = 1.0.
Jun 2020, Cir Cir. 2020, 569-575, https://cirugiaycirujanos.com/frame_esp.php?id=358, https://c19p.org/sosagarcia
348. Luo et al., COVID-19 in patients with lung cancer
48 patient HCQ late treatment study: 2% higher mortality (p=0.99).Analysis of hospitalized lung cancer patients with 35 of 48 taking HCQ, mortality OR 1.03, p = 0.99.
Jun 2020, Annals of Oncology, 1386-1396, https://www.annalsofoncology.org/article/S0923-7534(20)39894-X/fulltext, https://c19p.org/luo
349. Cassione et al., COVID-19 infection in a northern-Italian cohort of systemic lupus erythematosus assessed by telemedicine
165 patient HCQ prophylaxis study: 50% more cases (p=0.59).Survey of 165 SLE patients, 127 on HCQ. 8 patients with suspected COVID-19 and 4 confirmed cases. No mortality, one ICU case. 7 patients had no symptoms despite contact with a COVID-19 patient. No adjustment for concomitant medications or severity of SLE. Confounding by indication.
May 2020, Annals of the Rheumatic Diseases, https://ard.bmj.com/content/early/2020/05/23/annrheumdis-2020-217717.info, https://c19p.org/cassione
350. Geleris et al., Observational Study of Hydroxychloroquine in Hospitalized Patients with Covid-19
1,446 patient HCQ late treatment study: 4% higher combined mortality/intubation (p=0.76).Before propensity matching, 38 control patients had hypertension. After propensity matching, 146 patients had hypertension (Table 1). Even if all propensity matched control patients had hypertension, the control prevalence would only be 14% compared to 49% for treatment. Since patients with hypertension are at much greater risk of mortality (HR 2.12, see [academic.oup.com]), this appears to invalidate the results. Observational study of 1,446 hospitalized patients showing no significant effect on a combined intubation/death outcome for late treatment. However, secondary analysis shows the success of HCQ was hidden by combining intubation and death - death / (combined death/intubation) for HCQ was 60% vs. control 89%, for details see: [twitter.com]. RCT recommended. No AZ or Zinc. HCQ group much sicker - patients already in mild/moderate ARDS, most of the control group not in ARDS. Control cases received other therapeutics.
May 2020, NEJM, May 7, 2020, https://www.nejm.org/doi/full/10.1056/NEJMoa2012410, https://c19p.org/geleris
351. de la Iglesia et al., Hydroxicloroquine for pre-exposure prophyylaxis for SARS-CoV-2
1,375 patient HCQ prophylaxis study: 43% more cases (p=0.15).Analysis of autoimmune disease patients on HCQ, compared to a control group from the general population (matched on age and sex, but not adjusted for autoimmune disease), showing non-significant differences between groups. Other research shows that the risk of COVID-19 for systemic autoimmune disease patients is much higher overall, Ferri et al. show OR 4.42, p<0.001 [Ferri], which is the observed real-world risk, taking into account factors such as these patients potentially being more careful to avoid exposure. If we adjust for the different baseline risk, the mortality result becomes RR 0.35, p=0.23, suggesting a substantial benefit for HCQ treatment (as shown in other studies).
Sep 2020, medRxiv, https://www.medrxiv.org/content/10.1101/2020.08.31.20185314v1, https://c19p.org/delaiglesia
352. Uyaroğlu et al., Comparison of Favipiravir to Hydroxychloroquine Plus Azithromycin in the Treatment of Patients with Non-critical COVID-19: A Single-center, Retrospective, Propensity Score-matched Study
84 patient HCQ late treatment PSM study: 200% higher mortality (p=1), 67% lower ICU admission (p=1), and 10% shorter hospitalization (p=0.9).PSM retrospective 260 late stage hospitalized COVID-19 pneumonia patients in Turkey, showing no significant difference between favipiravir and HCQ.
Mar 2022, Acta Medica, https://actamedica.org/index.php/actamedica/article/view/719, https://c19p.org/uyaroglu
353. Erden et al., COVID-19 outcomes in patients with antiphospholipid syndrome: a retrospective cohort study
9 patient HCQ prophylaxis study: 75% lower hospitalization (p=0.23).Retrospective 9 COVID-19 patients with antiphospholipid syndrome in Turkey, showing no significant differences based on existing HCQ treatment.
Jan 2022, Bratislava Medical J., http://www.elis.sk/index.php?page=shop.product_details&flypage=flypage.tpl&product_id=7533&category_id=179&option=com_virtuemart&vmcchk=1&Itemid=1, https://c19p.org/erden
354. Bhatt et al., Hydroxychloroquine Prophylaxis against Coronavirus Disease-19: Practice Outcomes among Health-Care Workers
927 patient HCQ prophylaxis study: 49% more cases (p=0.02).Observational study of 927 low-risk healthcare workers in India, 731 volunteering for weekly HCQ prophylaxis, showing higher cases with treatment in unadjusted results. Clinical outcome was in the protocol, however no information on which patients were symptomatic is provided. There were no adverse events and no hospitalizations or deaths. Adherence was very low, decreasing weekly, with almost all participants discontinuing by week 11. The majority of infections occurred in later weeks when adherence was very low, and there was no per protocol analysis. #ECR/206/Inst/GJ/2013/RR-20.
Aug 2021, medRxiv, https://www.medrxiv.org/content/10.1101/2021.08.02.21260750v1, https://c19p.org/bhatt
355. Li et al., Treatment of COVID-19 patients with hydroxychloroquine or chloroquine: A retrospective analysis
37 patient HCQ late treatment study: 40% slower viral clearance (p=0.06).Small retrospective database analysis of 37 late stage patients hospitalized in an intensive care center in China, not finding a significant difference in viral shedding. Pateints were all in serious condition. There was only one death however the group is not specified. Confounding by indication is likely.
Jan 2021, Research Square, https://www.researchsquare.com/article/rs-119202/v1, https://c19p.org/li2
356. Komissarov et al., Hydroxychloroquine has no effect on SARS-CoV-2 load in nasopharynx of patients with mild form of COVID-19
36 patient HCQ late treatment study: 25% worse viral load (p=0.45).Small late stage (7-10 days post symptoms) study of nasal swab RNA with 12 control and 33 patients, showing no significant differences (significant reduction in viral load is seen in both groups). The groups are not comparable, with significant differences seen between hospitalized and non-hospitalized patients. 9 of 10 hospitalized patients were in the HCQ group and only one in the control group. 2 additional control patients were added between the first and second version of this preprint (including the only hospitalized control patient).
Jun 2020, medRxiv, https://www.medrxiv.org/content/10.1101/2020.06.30.20143289v1, https://c19p.org/komissarov
357. Guillaume et al., Antirheumatic Drug Intake Influence on Occurrence of COVID-19 Infection in Ambulatory Patients with Immune-Mediated Inflammatory Diseases: A Cohort Study
459 patient HCQ prophylaxis study: 2% higher hospitalization (p=1) and 3% more cases (p=0.96).Retrospective 459 SLE, RA, SjS, or PsA patients in France, showing no significant difference with HCQ treatment. However, the statistical analysis shows significant mismatches with prior research, which may be due to overfitting with the limited data and very small number of events. For example, the analysis estimates lower risk OR 0.72 for age, and shows very different relative risks of SLE, RA, SjS, or PsA compared to other research. We note the very different distribution of diseases in the groups, for example there is a much higher prevalence of PsA in the no HCQ group. The inaccurate estimations of risk for the different diseases and for age likely makes the adjusted analysis very inaccurate.
Sep 2021, Rheumatology and Therapy, https://link.springer.com/10.1007/s40744-021-00373-1, https://c19p.org/guillaume
358. Stewart et al., COVID-19 Evidence Accelerator: A parallel analysis to describe the use of Hydroxychloroquine with or without Azithromycin among hospitalized COVID-19 patients
11,157 patient HCQ late treatment study: 28% higher mortality (p=0.03) and 29% higher ventilation (p=0.09).Retrospective analysis of seven databases in the USA, showing higher mortality with treatment. Results contradict strong evidence from the RECOVERY/SOLIDARITY trials, suggesting substantial confounding by indication. Time based confounding is very likely because HCQ became highly controversial and usage dramatically declined over the time covered, while overall treatment protocols during this period improved dramatically, i.e., more control patients likely come later in the period when treatment protocols were greatly improved. This study includes anyone PCR+ during or prior to their visit, and anyone with ICD-10 COVID-19 codes which includes asymptomatic PCR+ patients, therefore some patients in the control groups may be asymptomatic with regards to SARS-CoV-2, but in the hospital for another reason. Authors do not mention the possibility of any of these likely confounding factors.
Mar 2021, PLoS ONE, https://journals.plos.org/plosone/article?id=10.1371/journal.pone.0248128, https://c19p.org/stewart
359. Vivanco-Hidalgo et al., Incidence of COVID-19 in patients exposed to chloroquine and hydroxychloroquine: results from a population-based prospective cohort in Catalonia, Spain, 2020
20,238 patient HCQ prophylaxis study: 46% higher hospitalization (p=0.1) and 8% more cases (p=0.5).Retrospective database analysis of chronic HCQ users and matched control patients, failing to match or adjust for the very different baseline risk for systemic autoimmune disease patients. Other research shows that the risk of COVID-19 for systemic autoimmune disease patients is much higher overall, Ferri et al. show OR 4.42, p<0.001 [Ferri].
Mar 2021, Eurosurveillance, https://www.eurosurveillance.org/content/10.2807/1560-7917.ES.2021.26.9.2001202, https://c19p.org/vivancohidalgo
360. Bosaeed et al., Favipiravir and Hydroxychloroquine Combination Therapy in Patients with Moderate to Severe COVID19 (FACCT Trial): An Open-Label, Multicenter, Randomized, Controlled Trial
254 patient HCQ late treatment RCT: 4% lower mortality (p=0.91), 8% higher ventilation (p=0.78), 31% higher ICU admission (p=0.24), and 29% slower recovery (p=0.29).RCT 254 very late stage (93% on oxygen, 17% in ICU at baseline) hospitalized patients in Saudi Arabia not showing significant differences with HCQ+favipiravir treatment. Only SaO2 < 94% patients were eligible, however the actual SaO2 of enrolled patients is not provided.
Apr 2021, Infect. Dis. Ther., https://link.springer.com/epdf/10.1007/s40121-021-00496-6, https://c19p.org/bosaeed
361. De Luna et al., Clinical and Demographic Characteristics of COVID-19 Patients Admitted in a Tertiary Care Hospital in the Dominican Republic
150 patient HCQ late treatment study: 105% higher mortality (p=0.69).Retrospective 150 patients in the Dominican Republic, 132 treated with HCQ, showing higher mortality with treatment in unadjusted results. Confounding by indication is likely.
Dec 2020, medRxiv, https://www.medrxiv.org/content/10.1101/2020.12.11.20247437v1, https://c19p.org/deluna
362. McGrail et al., COVID-19 Case Series at UnityPoint Health St. Luke’s Hospital in Cedar Rapids, IA
75 patient HCQ late treatment study: 70% higher mortality (p=0.69).HCQ+AZ early in the epidemic had a fairly good success rate with few complications, 86% of HCQ patients survived and 92% of HCQ+AZ patients. Patients not receiving either had 93% survival but were not considered comparable because the treated groups were significantly more ill (100% hypoxic at admission vs. 59%) and this study does not adjust for the differences. Transition from an early intubation strategy to aggressive utilization of high flow nasal cannula and noninvasive ventilation (i.e, BiPAP) was successful in freeing up ICU resources.
Jul 2020, medRxiv, https://www.medrxiv.org/content/10.1101/2020.07.17.20156521v1, https://c19p.org/mcgrail
363. Barbosa et al., Clinical outcomes of hydroxychloroquine in hospitalized patients with COVID-19: a quasi-randomized comparative study
63 patient HCQ late treatment study: 147% higher mortality (p=0.58).Small retrospective study with 63 patients (32 treated with HCQ), showing no effectiveness, however the baseline state of each arm significantly differs. This preprint was submitted to NEJM but has not been published several months later.
Apr 2020, Preprint, https://www.sefq.es/_pdfs/NEJM_Hydroxychlorquine.pdf, https://c19p.org/barbosa
364. Lotfy et al., Use of Hydroxychloroquine in Patients with COVID-19: A Retrospective Observational Study
202 patient HCQ late treatment study: 25% higher mortality (p=0.76), 41% higher ventilation (p=0.34), and 17% higher ICU admission (p=0.53).Retrospective 202 patients in Saudi Arabia not showing significant differences with treatment. No information is provided on how patients were selected for treatment, there may be significant confounding by indication. Time varying confounding is also likely as HCQ became controversial during the period studied, therefore HCQ use was likely more frequent toward the beginning of the period, a time when overall treatment protocols were significantly worse.
Dec 2020, Turk. Thorac. J., https://turkthoracj.org/en/use-of-hydroxychloroquine-in-patients-with-covid-19-a-retrospective-observational-study-131729, https://c19p.org/lotfy
365. Burhan et al., Characteristics and outcomes of patients with severe COVID-19 in Indonesia: Lessons from the first wave
559 patient HCQ ICU study: 1% higher mortality (p=0.91).Retrospective 559 COVID-19 ICU patients in Indonesia, showing no difference in mortality with HCQ in unadjusted results.
Sep 2023, PLOS ONE, https://journals.plos.org/plosone/article?id=10.1371/journal.pone.0290964, https://c19p.org/burhan
366. Silva et al., Clinical-Epidemiology Aspect of Inpatients With Moderate or Severe COVID-19 in a Brazilian Macroregion: Disease and Countermeasures
395 patient HCQ late treatment study: 46% higher mortality (p=0.22).Retrospective 395 hospitalized patients in Brazil, showing higher mortality with HCQ treatment, without statistical significance.
May 2022, Frontiers in Cellular and Infection Microbiology, https://www.frontiersin.org/articles/10.3389/fcimb.2022.899702/full, https://c19p.org/silva3
367. Kokturk et al., The predictors of COVID-19 mortality in a nationwide cohort of Turkish patients
1,500 patient HCQ late treatment study: 4% higher mortality (p=0.97).Retrospective 1,500 hospitalized late stage (median SaO2 87.7) patients in Turkey, showing no significant difference with HCQ treatment.
Apr 2021, Respiratory Medicine, https://www.sciencedirect.com/science/article/pii/S0954611121001396, https://c19p.org/kokturk
368. Rivera et al., Utilization of COVID-19 Treatments and Clinical Outcomes among Patients with Cancer: A COVID-19 and Cancer Consortium (CCC19) Cohort Study
506 patient HCQ late treatment study: 2% higher mortality (p=0.92).Retrospective cancer patients, showing adjusted OR 1.03 [0.62-1.73] for HCQ. The study reports the number of HCQ+AZ patients but they do not provide results for HCQ+AZ (only HCQ + any other treatment). Significant confounding by indication and compassionate use is likely.
Jul 2020, Cancer Discovery, https://cancerdiscovery.aacrjournals.org/content/early/2020/09/12/2159-8290.CD-20-0941, https://c19p.org/rivera
37 patient HCQ late treatment study: 29% worse viral clearance (p=0.7).
2 very small studies with hospitalized patients in Taiwan. RCT with 21 treatment and 12 SOC patients. No mortality, or serious adverse effects. Median time to negative RNA 5 days versus 10 days SOC, p=0.4. Risk of PCR+ at day 14, RR 0.76, p = 0.71. Small retrospective study with 12 of 28 HCQ patients and 5 of 9 in the control group being PCR- at day 14, RR 1.29, p = 0.7. The RCT and retrospective study are listed separately [Chen, Chen].
Jul 2020, PLoS ONE, https://journals.plos.org/plosone/article?id=10.1371/journal.pone.0242763, https://c19p.org/chen26
370. Mahévas et al., Clinical efficacy of hydroxychloroquine in patients with covid-19 pneumonia who require oxygen: observational comparative study using routine care data
173 patient HCQ late treatment study: 20% higher mortality (p=0.75).Observational study of 181 patients with advanced disease requiring oxygen showing no benefit for HCQ. Power of study appears too low to support conclusions [bmj.com]. None of the 15 patients receiving HCQ+AZ were transferred to intensive care or died compared to 23% overall.
May 2020, BMJ 2020, https://www.bmj.com/content/369/bmj.m1844, https://c19p.org/mahevas
371. Rosenberg et al., Association of Treatment With Hydroxychloroquine or Azithromycin With In-Hospital Mortality in Patients With COVID-19 in New York State
1,483 patient HCQ late treatment study: 35% higher mortality (p=0.31).Retrospective observational late stage study showing no significant differences but calling for clinical trials. Zervos et al. [ijidonline.com] point out serious limitations that they say should be corrected on the record: patients receiving HCQ with or without AZ were overall sicker on presentation and had multiple other risk factors including much higher risk based on ethnicity; patients receiving HCQ were more likely to be obese, diabetic, have chronic lung disease, and cardiovascular conditions; yet these sicker patients had approximately the same mortality rates compared to patients with a milder course of the disease and less risk factors. However, the authors conclude that "there are no significant benefits." It is noteworthy that HCQ was associated with a significant survival benefit in a larger cohort of patients from New York City as reported by [Mikami]. See also [worldtribune.com].
May 2020, JAMA, May 11, 2020, https://jamanetwork.com/journals/jama/fullarticle/2766117, https://c19p.org/rosenberg
372. Auld et al., ICU and ventilator mortality among critically ill adults with COVID-19
217 patient HCQ late treatment study: 3% higher mortality (p=1).Retrospective 217 critically ill patients, 114 receiving HCQ, showing no significant difference in mortality.
Apr 2020, Critical Care Medicine, https://journals.lww.com/ccmjournal/Fulltext/2020/09000/ICU_and_Ventilator_Mortality_Among_Critically_Ill.35.aspx, https://c19p.org/auld
373. Souza-Silva et al., Dados de Vida Real sobre o Uso da Hidroxicloroquina ou da Cloroquina Combinadas ou Não à Azitromicina em Pacientes com Covid-19: Uma Análise Retrospectiva no Brasil
1,346 patient HCQ late treatment study: 5% higher mortality (p=0.68), 21% higher ventilation (p=0.08), 9% higher ICU admission (p=0.31), and 12% longer hospitalization (p=0.03).Retrospective 7,580 hospitalized patients in Brazil, showing longer hospitalization, and no significant difference in mortality, mechanical ventilation, and ICU admission with HCQ treatment. Authors note confounding by indication due to selected use in a compassionate use context. Authors match only on age, sex, cardiovascular comorbidities, and in-hospital use of corticosteroid, and only 10% of patients received HCQ/CQ, therefore confounding by indication is likely to be significant. A different matching list is included in the text, but neither includes COVID-19 severity. In the first line of the abstract authors falsely state that there is no evidence of benefit for HCQ treatment. While misrepresenting prior research is common, this is an extreme case and raises concern for validity of the analysis. In reality controlled studies show statistically significant positive results for one or more outcomes (including RCTs). Authors discussion of prior research shows similar bias.
Sep 2023, Arquivos Brasileiros de Cardiologia, https://abccardiol.org/article/dados-de-vida-real-sobre-o-uso-da-hidroxicloroquina-ou-da-cloroquina-combinadas-ou-nao-a-azitromicina-em-pacientes-com-covid-19-uma-analise-retrospectiva-no-brasil/, https://c19p.org/souzasilva
374. Huh et al., Association of prescribed medications with the risk of COVID-19 infection and severity among adults in South Korea
44,046 patient HCQ prophylaxis study: 97% higher progression (p=0.11) and 6% fewer cases (p=0.82).Retrospective database analysis with 17 cases for existing HCQ users and 5 severe cases, showing no significant difference for cases and higher risk for severe cases. However, HCQ users are likely systemic autoimmune disease patients and authors do not adjust for the very different baseline risk for these patients. Other research shows that the risk of COVID-19 for systemic autoimmune disease patients is much higher overall, Ferri et al. show OR 4.42, p<0.001 [Ferri].
Dec 2020, Int. J. Infectious Diseases, https://www.sciencedirect.com/science/article/pii/S1201971220325650, https://c19p.org/huh2
325 patient HCQ late treatment study: 890% higher progression (p=0.03).
Retrospective 325 hospitalized COVID-19 patients in Malaysia, showing higher progression with HCQ, however the groups are not comparable. 17 HCQ vs. 3 control patients had severity category ≥3 at baseline (7 vs. 0 for severity ≥4).
Mar 2023, Malaysian J. Medicine and Health Sciences, https://medic.upm.edu.my/upload/dokumen/2023032211275502_MJMHS_0551.pdf, https://c19p.org/ho2
376. Çivriz Bozdağ et al., Clinical Characteristics and Outcome of COVID-19 in Turkish Hematological Malignancy Patients
175 patient HCQ late treatment study: 399% higher mortality (p=0.003).Retrospective 340 patients with hematological malignancy in Turkey, showing higher mortality with HCQ treatment. Confounding by time is likely because more HCQ patients were earlier in time when overall treatment protocols were significantly worse.
Sep 2021, Turk. J. Haematol., https://pubmed.ncbi.nlm.nih.gov/34521187/, https://c19p.org/civrizbozdag
377. Alotaibi et al., Effectiveness and Safety of Favipiravir Compared to Hydroxychloroquine for Management of Covid-19: A Retrospective Study
437 patient HCQ late treatment study: 134% higher mortality (p=0.05).Retrospective hospitalized patients in Saudi Arabia, showing lower mortality with favipiravir compared to HCQ, not quite reaching statistical significance. Authors do not indicate the factors behind which therapy was chosen. May be subject to significant confounding by indication and confounding by time.
Sep 2021, Int. J. General Medicine, https://www.dovepress.com/getfile.php?fileID=73585, https://c19p.org/alotaibi
378. Tamura et al., Outcome and death risk of diabetes patients with Covid-19 receiving pre-hospital and in-hospital metformin therapies
188 patient HCQ late treatment study: 299% higher mortality (p=0.04).Retrospective 188 hospitalized patients in Brazil, showing higher risk of mortality with HCQ. Relatively few patients received HCQ. The results are likely subject to confounding by indication with treatment more likely for severe cases, and severity was not used in adjustments. Confounding by time is likely, with declining use of HCQ and improving SOC over the study period.
Jul 2021, Diabetology & Metabolic Syndrome, https://dmsjournal.biomedcentral.com/articles/10.1186/s13098-021-00695-8, https://c19p.org/tamurah
379. Saib et al., Lack of efficacy of hydroxychloroquine and azithromycin in patients hospitalized for COVID-19 pneumonia: A retrospective study
104 patient HCQ late treatment PSM study: 125% higher combined mortality/intubation (p=0.23).203 hospitalized patients in France, not showing significant differences with treatment. Confounding by indication is likely. Authors do not discuss confounding.
Jun 2021, PLOS ONE, https://journals.plos.org/plosone/article?id=10.1371/journal.pone.0252388, https://c19p.org/saib
380. Sammartino et al., Predictors for inpatient mortality during the first wave of the SARS-CoV-2 pandemic: A retrospective analysis
328 patient HCQ late treatment PSM study: 240% higher mortality (p=0.002).Retrospective 1,108 hospitalized patients in New York showing significantly higher mortality with HCQ treatment. Time based confounding is very likely because HCQ became increasingly controversial and less used over the time covered (Mar - Jun 2020), while overall treatment protocols during this period improved dramatically, i.e., more control patients likely come later in the period when treatment protocols were greatly improved. Authors note that for every week or month later that a person was admitted, their risk of death dropped by 16% and 49%, respectively, yet they do not consider time based confounding.
May 2021, PLOS One, https://journals.plos.org/plosone/article?id=10.1371/journal.pone.0251262, https://c19p.org/sammartino
381. Mohandas et al., Clinical review of COVID-19 patients presenting to a quaternary care private hospital in South India: A retrospective study
3,345 patient HCQ late treatment study: 81% higher mortality (p=0.007).Retrospective 3,345 hospitalized patients in India, 11.5% treated with HCQ, showing unadjusted higher mortality with treatment. Confounding by indication and time based confounding (due to declining use over the period when overall treatment protocols improved dramatically) are likely.
Apr 2021, Clinical Epidemiology and Global Health, https://www.sciencedirect.com/science/article/pii/S2213398421000555, https://c19p.org/mohandas
382. Sands et al., No clinical benefit in mortality associated with hydroxychloroquine treatment in patients with COVID-19
1,669 patient HCQ late treatment study: 70% higher mortality (p=0.01).Retrospective database analysis of 1,669 patients in the US showing OR 1.81, p = 0.01. Confounding by indication is likely. COVID-19 was determined via PCR+ results, therefore authors include patients asymptomatic for COVID-19, but in the hospital for other reasons. While authors adjust for severity, the method used is very poor. 93.5% of patients are classified as "mild", which is patients with no documented care in a critical care unit within 8 hours of admission. Therefore almost all patients are in the same category, and those in a different category may be due to symptoms unrelated to COVID-19. Lower bias toward male patients in the control group also agrees with the hypothesis that the control group is made up of more people that were in hospital for another reason. Since the analysis covers the initial period of the pandemic in the USA, it is likely that HCQ was used more often earlier in the analysis period when treatment protocols were considerably worse. It's..
Dec 2020, Int. J. Infectious Diseases, https://www.sciencedirect.com/science/article/pii/S1201971220325832, https://c19p.org/sands
383. Psevdos et al., Corona Virus Disease-19 (COVID-19) in a Veterans Affairs Hospital at Suffolk County, Long Island, New York
67 patient HCQ late treatment study: 63% higher mortality (p=0.52).Retrospective 67 hospitalized patients in the USA showing non-statistically significant unadjusted increased mortality with HCQ. Confounding by indication is likely. Time varying confounding is likely. HCQ became controversial and was suspended during the end of the period studied, therefore HCQ use was likely more frequent toward the beginning of the study period, a time when overall treatment protocols were significantly worse.
Dec 2020, Open Forum Infectious Diseases, https://academic.oup.com/ofid/article/7/Supplement_1/S330/6057008, https://c19p.org/psevdos
384. Texeira et al., Characteristics and outcomes of COVID-19 patients admitted to a regional health system in the southeast
161 patient HCQ late treatment study: 79% higher mortality (p=0.1).Retrospective 161 hospitalized patients in the USA showing non-statistically significant unadjusted increased mortality with HCQ. Confounding by indication is likely. Time varying confounding is likely. HCQ became controversial and was suspended towards the end of the period studied, therefore HCQ use was likely more frequent toward the beginning of the study period, a time when overall treatment protocols were significantly worse.
Dec 2020, Open Forum Infectious Diseases, https://academic.oup.com/ofid/article/7/Supplement_1/S251/6058327, https://c19p.org/teixeira
385. SOLIDARITY Trial Consortium et al., Repurposed antiviral drugs for COVID-19; interim WHO SOLIDARITY trial results
1,853 patient HCQ late treatment RCT: 19% higher mortality (p=0.23).WHO SOLIDARITY open-label trial with 954 very late stage (64% on oxygen/ventilation) HCQ patients, mortality relative risk RR 1.19 [0.89-1.59], p=0.23. HCQ dosage very high as in RECOVERY, 1.6g in the first 24 hours, 9.6g total over 10 days, only 25% less than the high dosage that Borba et al. show greatly increases risk (OR 2.8) [Borba]. Authors state they do not know the weight or obesity status of patients to analyze toxicity (since they do not adjust dosage based on patient weight, toxicity may be higher in patients of lower weight). KM curves show a spike in HCQ mortality days 5-7, corresponding to ~90% of the total excess seen at day 28 (a similar spike is seen in the RECOVERY trial). Almost all excess mortality is from ventilated patients. Authors refer to a lack of excess mortality in the first few days to suggest a lack of toxicity, but they are ignoring the very long half-life of HCQ and the dosing regimen - much higher levels of HCQ will be reached later. Increased..
Oct 2020, SOLIDARITY Trial Consortium, NEJM, https://www.nejm.org/doi/full/10.1056/NEJMoa2023184, https://c19p.org/solidarity
386. Laplana et al., Lack of protective effect of chloroquine derivatives on COVID-19 disease in a Spanish sample of chronically treated patients
638 patient HCQ prophylaxis study: 56% more cases (p=0.24).Survey of 319 autoimmune disease patients taking CQ/HCQ with 5.3% COVID-19 incidence, compared to a control group from the general population (matched on age, sex, and region, but not adjusted for autoimmune disease), with 3.4% incidence. It not clear why authors did not compare with autoimmune patients not on CQ/HCQ. Other research shows that the risk of COVID-19 for systemic autoimmune disease patients is much higher overall, Ferri et al. show OR 4.42, p<0.001 [Ferri], which is the observed real-world risk, taking into account factors such as these patients potentially being more careful to avoid exposure. If we adjust for the different baseline risk, the result becomes RR 0.36, p<0.001, suggesting a substantial benefit for HCQ/CQ treatment (as shown in other studies). There may also be significant survey bias - those experiencing COVID-19 may be more likely to respond to the survey. Authors note that they "could not eliminate completely the possibility of some bias due to the..
Sep 2020, PLOS ONE, https://journals.plos.org/plosone/article?id=10.1371/journal.pone.0243598, https://c19p.org/laplana
387. Kelly et al., Clinical outcomes and adverse events in patients hospitalised with COVID-19, treated with off-label hydroxychloroquine and azithromycin
134 patient HCQ late treatment study: 143% higher mortality (p=0.03).Retrospective 82 hospitalized patients HCQ/AZ, 52 SOC, not finding statistically significant differences. Confounding by indication - authors note that the HCQ/AZ patients were more severely ill, and do not attempt to adjust for confounders.
Jul 2020, British J. Clinical Pharmacology, https://bpspubs.onlinelibrary.wiley.com/doi/full/10.1111/bcp.14482, https://c19p.org/kelly
388. Cravedi et al., COVID-19 and kidney transplantation: Results from the TANGO International Transplant Consortium
144 patient HCQ late treatment study: 53% higher mortality (p=0.17).Analysis of 144 hospitalized kidney transplant patients showing HCQ mortality HR 1.53, p = 0.17. Subject to confounding by indication.
Jul 2020, American J. Transplantation, https://onlinelibrary.wiley.com/doi/full/10.1111/ajt.16185, https://c19p.org/cravedi
389. Kuderer et al., Clinical impact of COVID-19 on patients with cancer (CCC19): a cohort study
928 patient HCQ late treatment study: 134% higher mortality (p<0.0001).Retrospective 928 cancer patients, showing HCQ OR 1.06 [0.51-2.20]. HCQ+AZ OR 2.93 [1.79-4.79]. The relative risks of different therapies suggest that the results are overly affected by confounding by indication. Authors note: HCQ+AZ might not be the cause of increased mortality, but instead these were given to patients with more severe COVID-19.
May 2020, Lancet, June 20, 2020, https://www.thelancet.com/journals/lancet/article/PIIS0140-6736(20)31187-9/fulltext, https://c19p.org/kuderer
262 patient HCQ prophylaxis study: 17% higher mortality (p=0.8), 78% higher combined mortality/ICU admission (p=0.21), and 45% higher hospitalization (p=0.12).
Retrospective 71 chronic HCQ patients compared with 191 matched controls, analyzing only those with a highly suspected or confirmed diagnosis of COVID-19. No significant difference was found in outcomes, however matching failed with extreme confounding - 77.5% of HCQ patients with systemic autoimmune diseases vs. 21.5% of control patients. Other research shows that the risk of COVID-19 for systemic autoimmune disease patients is much higher overall, Ferri et al. show OR 4.42, p<0.001 [Ferri].
Jan 2021, Revue du Rhumatisme, https://www.sciencedirect.com/science/article/abs/pii/S1169833021002489, https://c19p.org/trefond
391. RECOVERY Collaborative Group et al., Effect of Hydroxychloroquine in Hospitalized Patients with COVID-19: Preliminary results from a multi-centre, randomized, controlled trial
4,716 patient HCQ late treatment RCT: 9% higher mortality (p=0.15) and 15% higher ventilation (p=0.19).RECOVERY trial finds no significant benefit for very late stage (9 days after symptom onset) very sick patients. Results may be due to the unusually high dosage used (9.2g total over 10 days) [twitter.com, twitter.com]. The overall dosage used is only 23% less than the high dosage that Borba et al. show greatly increases risk (OR 2.8) [Borba]. Authors do not report results based on weight, BMI, or related conditions such as diabetes, which may provide additional evidence of toxic dosages. Authors do not adjust dosage based on patient weight, so toxicity may be higher in patients of lower weight. KM curves show a spike in HCQ mortality days 5-8, corresponding to ~85% of the total excess seen at day 28 (a similar spike is seen in the SOLIDARITY trial). Authors note: "we did not observe excess mortality in the first 2 days of treatment ... when early effects of dose-dependent toxicity might be expected", but they are ignoring the very long half-life of HCQ and the dosing..
Jun 2020, RECOVERY Collaborative Group, NEJM, https://www.nejm.org/doi/full/10.1056/NEJMoa2022926, https://c19p.org/recovery
392. Juneja et al., Hydroxychloroquine pre-exposure prophylaxis provides no protection against COVID-19 among health care workers: a cross-sectional study in a tertiary care hospital in North India
2,200 patient HCQ prophylaxis study: 142% higher severe cases (p=0.59) and 6% more cases (p=0.67).Retrospective 2,200 healthcare workers in India, 996 taking HCQ prophylaxis, showing no significant differences. There were large differences in the occupation of participants and therefore exposure, and the authors make no adjustments.
Jan 2022, J. Basic and Clinical Physiology and Pharmacology, https://www.degruyter.com/document/doi/10.1515/jbcpp-2021-0221/html, https://c19p.org/juneja
393. Awad et al., Impact of hydroxychloroquine on disease progression and ICU admissions in patients with SARS-CoV-2 infection
336 patient HCQ late treatment study: 19% higher mortality (p=0.6), 461% higher ventilation (p<0.0001), and 463% higher ICU admission (p<0.0001).This paper has inconsistent values - the number of treatment and control patients differs in the text and Table 1, we have used treatment 188 and control 148. Retrospective 336 hospitalized patients in the USA showing higher mortality, ICU admission, and intubation with treatment. Confounding by indication is likely. Time varying confounding is also likely due to declining usage over the early period when overall treatment protocols were also improving dramatically. Authors and reviewers appear to be unfamiliar with either of these.
Feb 2021, American J. Health-System Pharmacy, https://academic.oup.com/ajhp/advance-article/doi/10.1093/ajhp/zxab056/6144083, https://c19p.org/awad
394. Oztas et al., Frequency and Severity of COVID-19 in Patients with Various Rheumatic Diseases Treated Regularly with Colchicine or Hydroxychloroquine
650 patient HCQ prophylaxis study: 215% higher hospitalization (p=0.36), 40% more symptomatic cases (p=0.44), and 5% more cases (p=0.88).Retrospective 317 HCQ users and 333 household contacts, showing higher risk with HCQ.
Mar 2022, J. Medical Virology, https://onlinelibrary.wiley.com/doi/10.1002/jmv.27731, https://c19p.org/oztas
395. Gerlovin et al., Pharmacoepidemiology, Machine Learning and COVID-19: An intent-to-treat analysis of hydroxychloroquine, with or without azithromycin, and COVID-19 outcomes amongst hospitalized US Veterans
1,199 patient HCQ late treatment study: 22% higher mortality (p=0.18) and 55% higher ventilation (p=0.02).Retrospective 1,769 hospitalized patients in the USA showing no significant differences for HCQ, and higher intubation for HCQ+AZ.
Jun 2021, American J. Epidemiology, https://academic.oup.com/aje/advance-article/doi/10.1093/aje/kwab183/6308675, https://c19p.org/gerlovin
396. Hofmann-Winkler et al., Camostat Mesylate May Reduce Severity of Coronavirus Disease 2019 Sepsis: A First Observation
11 patient HCQ ICU study: 140% higher mortality (p=0.55), 157% longer ICU admission, and 125% worse recovery.Retrospective 11 critically ill COVID-19 ICU patients with organ failure treated with camostat mesylate (6 patients) or HCQ (5 patients). Over an 8 day period, the severity of COVID-19 decreased in the camostat group as measured by a decline in the SOFA score, inflammatory markers, and improvement in oxygenation. A similar effect was not seen in the HCQ group.
Nov 2020, Critical Care Explorations, https://journals.lww.com/10.1097/CCE.0000000000000284, https://c19p.org/hofmannwinklerh
397. Shahrin et al., Hospital-Based Quasi-Experimental Study on Hydroxychloroquine Pre-Exposure Prophylaxis for COVID-19 in Healthcare Providers with Its Potential Side-Effects
336 patient HCQ prophylaxis study: 88% more cases (p=0.09).Retrospective 230 low risk healthcare workers taking HCQ prophylaxis, and 106 that declined, showing higher cases without statistical significance. No case severity information is provided. The point estimate favored HCQ when excluding the first 14 days and including participants that worked for at least 16 days. Authors note a significant dose response relationship.
Dec 2022, Life, https://www.mdpi.com/2075-1729/12/12/2047, https://c19p.org/shahrin
398. Burdick et al., Is Machine Learning a Better Way to IdentifyCOVID-19 Patients Who Might Benefit fromHydroxychloroquineTreatment?—The IDENTIFY Trial
290 patient HCQ late treatment study: 59% higher mortality (p=0.12).290 patient observational trial in the USA, not showing a significant difference with HCQ treatment overall, but showing significantly lower mortality in a subgroup of patients where HCQ is expected to be beneficial based on a machine learning algorithm.
Nov 2020, J. Clinical Medicine, https://www.mdpi.com/2077-0383/9/12/3834, https://c19p.org/burdick
399. Pablos et al., Clinical outcomes of hospitalised patients with COVID-19 and chronic inflammatory and autoimmune rheumatic diseases: a multicentric matched cohort study
228 patient HCQ late treatment study: 126% higher severe cases (p=0.002).Retrospective 228 rheumatic disease and 228 non-rheumatic disease hospitalized COVID-19 patients in Spain, showing higher risk of severe COVID-19 with HCQ treatment.
Aug 2020, Annals of the Rheumatic Diseases, https://ard.bmj.com/lookup/doi/10.1136/annrheumdis-2020-218296, https://c19p.org/pablos
400. Kalligeros et al., Hydroxychloroquine use in hospitalised patients with COVID-19: An observational matched cohort study
108 patient HCQ late treatment study: 67% higher mortality (p=0.57).Small retrospective database analysis of 36 patients receiving HCQ not showing significant differences. Confounding by indication is likely.
Aug 2020, J. Global Antimicrobial Resistance, https://www.sciencedirect.com/science/article/pii/S2213716520301934, https://c19p.org/kalligeros
401. Mallat et al., Hydroxychloroquine is associated with slower viral clearance in clinical COVID-19 patients with mild to moderate disease: A retrospective study
34 patient HCQ late treatment study: 203% slower viral clearance (p=0.02).Very small retrospective analysis of 34 patients finding slower binary PCR viral clearance with HCQ. No information on severity for treatment versus control is provided. No deaths, ICU admission, or mechanical ventilation. Binary PCR does not distinguish replication-competence. HCQ treatment started very late for many patients with >= 9 days for 25%.
May 2020, Medicine, https://journals.lww.com/md-journal/Fulltext/2020/12240/Hydroxychloroquine_is_associated_with_slower_viral.34.aspx, https://c19p.org/mallat
402. Tirupakuzhi Vijayaraghavan et al., Hydroxychloroquine plus personal protective equipment versus personal protective equipment alone for the prevention of laboratory-confirmed COVID-19 infections among healthcare workers: a multicentre, parallel-group randomised controlled trial from India
414 patient HCQ prophylaxis RCT: 196% higher progression (p=1), 52% lower hospitalization (p=0.62), and 14% fewer cases (p=0.73).Low-dose prophylaxis RCT with low-risk healthcare workers in India, showing no significant differences. Symptomatic case results are not provided. Followup was over 6 months, however treatment ended after 3 months. 21% of patients discontinued treatment before 3 months (Table S2).
May 2022, BMJ Open, https://bmjopen.bmj.com/lookup/doi/10.1136/bmjopen-2021-059540, https://c19p.org/tirupakuzhi
403. Ferreira et al., Outcomes associated with Hydroxychloroquine and Ivermectin in hospitalized patients with COVID-19: a single-center experience
192 patient HCQ late treatment study: 151% higher mortality (p=0.03) and 46% higher combined mortality/intubation (p=0.23).Retrospective 230 hospitalized patients in Brazil showing higher mortality with HCQ treatment. Authors note that the treatments were more likely to be offered to sicker patients. Authors note that they do not know if treatment was started before or after ICU admission and intubation. Dosage is unknown.
Nov 2021, Revista da Associação Médica Brasileira, https://www.scielo.br/j/ramb/a/kzbmDvJqjJdQR9GfqK65CZs/, https://c19p.org/ferreira2h
404. Spivak et al., A Randomized Clinical Trial Testing Hydroxychloroquine for Reduction of SARS-CoV-2 Viral Shedding and Hospitalization in Early Outpatient COVID-19 Infection
367 patient HCQ late treatment RCT: 73% higher hospitalization (p=0.54), 20% improved recovery (p=0.19), and 17% improved viral clearance (p=0.19).Delayed publication of an early terminated late treatment RCT with low-risk (no mortality) outpatients in the USA, showing no significant differences with HCQ. Authors do not provide symptom onset data, but the subgroup analysis suggests that more patients may have been in the 5+ days group (the estimate for the 5+ days group has a smaller confidence interval, and the overall mean/median for HCQ is much closer to the 5+ days group). Treatment was started one day after enrollment according to Table S1 (authors report "commonly 1 day after randomization" in the text). This suggests that most patients were treated 6+ days after onset. Subgroup analysis for <5, ≥5 days is provided only for viral shedding duration, and shows improved results for earlier treatment. Adherence was only 66% (Figure 1). Publication was 21 months after the trial ended. Registered outcomes were modified November 2022, December 2022, and January 2023, all over a year after completion of the trial. For..
Mar 2023, Microbiology Spectrum, https://journals.asm.org/doi/10.1128/spectrum.04674-22, https://c19p.org/spivak
405. Schmidt et al., Association Between Androgen Deprivation Therapy and Mortality Among Patients With Prostate Cancer and COVID-19
477 patient HCQ late treatment PSM study: 333% higher mortality (p=0.0001) and 613% higher severe cases (p<0.0001).Retrospective 1,106 prostate cancer patients, showing higher mortality with HCQ treatment.
Nov 2021, JAMA Network Open, https://jamanetwork.com/journals/jamanetworkopen/fullarticle/2786026, https://c19p.org/schmidth
406. Barnabas et al., Hydroxychloroquine for Post-exposure Prophylaxis to Prevent Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2) Infection: A Randomized Trial
829 patient HCQ prophylaxis RCT: 27% more cases (p=0.33).Early terminated PEP RCT comparing HCQ and vitamin C with 781 low-risk patients (83% household contacts), reporting no significant differences. Different results were reported at IDWeek from the AIM results. The study enrolled people with their last exposure within 4 days, i.e., if someone was exposed for 30 days in a row, they could be enrolled anywhere from day 1 to day 34. Therefore many were likely infected earlier than the enrollment date. Note that PCR has a very high false negative rates, e.g., 100% on day 1 and 67% on day 4 here [ncbi.nlm.nih.gov]. 50% of infections were detected by day 4. With the PCR false negatives and treatment delays it is likely that a majority of infections happened before enrollment or before HCQ can reach therapeutic levels. Significantly more cases were caught at baseline in the control group (54 vs. 29 for HCQ) and excluded from analysis. The early presentation stated that therapy started one day after enrollment and study supplies were sent to the..
Dec 2020, Annals of Internal Medicine, https://www.acpjournals.org/doi/10.7326/M20-6519, https://c19p.org/barnabas
407. Self et al., Effect of Hydroxychloroquine on Clinical Status at 14 Days in Hospitalized Patients With COVID-19: A Randomized Clinical Trial
477 patient HCQ late treatment RCT: 6% higher mortality (p=0.85) and 3% worse 7-point scale results (p=0.87).Early terminated very late stage (65% on supplemental oxygen) RCT with 242 HCQ and 237 control patients showing no significant difference in outcomes. For the subgroup not on supplemental oxygen at baseline (relatively early treatment), the odds ratio for the 7 point outcome scale is: aOR 0.61 [0.34-1.08]. Dosage may be too low: Dose in first 24 hours - 1g (compare to Boulware et al. 2g) Dose in 5 days - 2.4g (compare to Boulware et al. 3.8g) Dosage note: Boulware 2g within 24 hours includes the second day dose. Note two important differences with the RECOVERY/SOLIDARITY dosage which is believed to be dangerously high - in RECOVERY/SOLIDARITY the total dose is much higher, which is problematic because the half-life of HCQ is very long, and it is given to patients that are already in very serious condition. Note the paper reports primary outcome values with OR>1 favoring HCQ, we have converted to OR<1 favoring HCQ. Subgroup analysis is in the supplemental appendix.
Nov 2020, JAMA, https://jamanetwork.com/journals/jama/fullarticle/2772922, https://c19p.org/self
408. Ulrich et al., Treating Covid-19 With Hydroxychloroquine (TEACH): A Multicenter, Double-Blind, Randomized Controlled Trial in Hospitalized Patients
128 patient HCQ late treatment RCT: 6% higher mortality (p=1) and 173% higher ICU admission (p=0.13).Small RCT on very late stage use of HCQ, with 48% on oxygen at baseline. 67 HCQ patients, 61 control. Baseline states were not comparable - 82% more HCQ patients had the highest severity at baseline, there was 32% more male HCQ patients, and 44% more control patients used AZ. The HCQ group also had significantly more patients with cerebrovascular disease, cardiovascular disease (non-hypertension), renal disease (non-dialysis), and a history of organ transplants.
Sep 2020, Open Forum Infectious Diseases, https://academic.oup.com/ofid/advance-article/doi/10.1093/ofid/ofaa446/5910201, https://c19p.org/ulrich
409. Babayigit et al., The association of antiviral drugs with COVID-19 morbidity: The retrospective analysis of a nationwide COVID-19 cohort
1,472 patient HCQ late treatment study: 112% higher ventilation (p=0.21), 53% higher ICU admission (p=0.33), and 17% longer hospitalization (p=0.05).Retrospective 1,472 hospitalized patients in Turkey, showing a higher risk of ICU admission and ventilation with HCQ, without statistical significance.
Aug 2022, Frontiers in Medicine, https://www.frontiersin.org/articles/10.3389/fmed.2022.894126/full, https://c19p.org/babayigith
410. Babalola et al., A Randomized Controlled Trial of Ivermectin Monotherapy Versus Hydroxychloroquine, Ivermectin, and Azithromycin Combination Therapy in Covid-19 Patients in Nigeria
60 patient HCQ late treatment RCT: 55% lower hospital discharge (p=0.2) and 10% improved viral clearance (p=0.78).Small RCT with 61 patients in Nigeria, all patients treated with ivermectin, zinc, and vitamin C, showing no significant improvements in recovery with the addition of HCQ+AZ.
Sep 2021, J. Infectious Diseases and Epidemiology, https://www.clinmedjournals.org/articles/jide/journal-of-infectious-diseases-and-epidemiology-jide-7-233.php?jid=jide, https://c19p.org/babalola2h
411. Syed et al., Pre-exposure Prophylaxis With Various Doses of Hydroxychloroquine Among Healthcare Personnel With High-Risk Exposure to COVID-19: A Randomized Controlled Trial
101 patient HCQ prophylaxis RCT: 60% more symptomatic cases (p=0.41) and 92% more cases (p=0.12).Small PrEP RCT of low risk healthcare workers, showing no significant differences. Authors report that there was no hospitalization, ICU care, or death from COVID-19, however table 3 of the preprint shows severe events labeled as "requiring hospitalization". Symptomatology and disease severity results in tables 3 and 4 appear inconsistent. NCT04359537.
May 2021, Cureus, https://www.cureus.com/articles/77806-pre-exposure-prophylaxis-with-various-doses-of-hydroxychloroquine-among-healthcare-personnel-with-high-risk-exposure-to-covid-19-a-randomized-controlled-trial, https://c19p.org/syed
412. Calderón et al., Treatment with hydroxychloroquine vs nitazoxanide in patients with COVID-19: brief report
44 patient HCQ late treatment study: 215% higher mortality (p=0.38), 652% higher ventilation (p=0.15), 145% higher ICU admission (p<0.0001), and 107% longer hospitalization (p=0.007).Planned RCT of HCQ vs. HCQ+nitazoxanide which was aborted due to the retracted Surgisphere paper. Authors retrospectively analyze a small set of HCQ vs. nitazoxanide patients (which were protocol deviations in the planned RCT), showing reduced hospitalization time and ICU admission with nitazoxanide.
Nov 2021, PAMJ - Clinical Medicine, https://www.clinical-medicine.panafrican-med-journal.com/content/article/7/15/full/, https://c19p.org/calderon2h
413. Rodrigues et al., Hydroxychloroquine plus azithromycin early treatment of mild COVID-19 in outpatient setting: a randomized, double-blinded, placebo-controlled clinical trial evaluating viral clearance
84 patient HCQ early treatment RCT: 14% improved viral clearance (p=0.15).RCT 84 low risk patients, 42 treated with HCQ/AZ, showing no significant differences. There was only one hospitalization which was in the treatment arm.
Aug 2021, Int. J. Antimicrobial Agents, https://www.sciencedirect.com/science/article/pii/S0924857921002065, https://c19p.org/rodrigues
414. Llanos-Cuentas et al., Hydroxychloroquine to prevent SARS-CoV-2 infection among healthcare workers: early termination of a phase 3, randomised, open-label, controlled clinical trial
68 patient HCQ prophylaxis RCT: 69% more cases (p=0.46).Early terminated healthcare worker PrEP RCT with only 68 patients and 8 cases, showing no significant difference with HCQ. No information on symptoms per group, case severity, or the timing of cases is provided.
Feb 2023, BMC Research Notes, https://bmcresnotes.biomedcentral.com/articles/10.1186/s13104-023-06281-7, https://c19p.org/llanoscuentas
415. Higgins et al., Long-term (180-Day) Outcomes in Critically Ill Patients With COVID-19 in the REMAP-CAP Randomized Clinical Trial
352 patient HCQ ICU RCT: 51% higher mortality (p=0.06).Long-term followup for the REMAP-CAP very late stage ICU trial, showing higher risk with HCQ, not quite reaching statistical significance.
Dec 2022, JAMA, https://jamanetwork.com/journals/jama/fullarticle/2799870, https://c19p.org/higgins
416. Barrat-Due et al., Evaluation of the Effects of Remdesivir and Hydroxychloroquine on Viral Clearance in COVID-19
93 patient HCQ late treatment RCT: 120% higher mortality (p=0.35).Small RCT in Norway showing no significant differences with HCQ treatment. Add-on trial to WHO Solidarity.
Jul 2021, Annals of Internal Medicine, https://www.acpjournals.org/doi/10.7326/M21-0653, https://c19p.org/barratdue
418. Schwartz et al., Assessing the efficacy and safety of hydroxychloroquine as outpatient treatment of COVID-19: a randomized controlled trial
179 patient HCQ late treatment RCT: 37% improved recovery (p=0.15).Small early terminated late treatment RCT showing no significant differences. The HCQ group was a median of 7 days from symptom onset at baseline, which may not include the delay delivering the medication. From the 4 HCQ hospitalizations, only one is in the per-protocol analysis, and that patient was hospitalized one day after randomization (authors do not specify if the patient received and took any HCQ before the hospitalization). The trial was terminated early due to the fraudulent Lancet article (wording here is notably different between the submitted and published versions). Per-protocol analysis, the submitted version, and the peer-review comments (two reviewers, only one with substantial feedback) are in the supplementary material. Long-term recovery results are reported in [Ganesh]. When a patient reported a symptom, they were asked whether they were still experiencing that symptom, and to choose between these three options when comparing the symptom to their pre-COVID-19..
Jun 2021, CMAJ Open, http://cmajopen.ca/content/9/2/E693.full, https://c19p.org/schwartz2
419. Réa-Neto et al., An open-label randomized controlled trial evaluating the efficacy of chloroquine/hydroxychloroquine in severe COVID-19 patients
105 patient HCQ late treatment RCT: 57% higher mortality (p=0.2), 115% higher ventilation (p=0.03), and 147% worse recovery (p=0.02).Early terminated very late stage (99% on oxygen, 81% in ICU, 18% on mechanical ventilation at baseline) RCT with 24 CQ patients, 29 HCQ, and 52 control patients, showing worse clinical outcomes with treatment. NCT04420247.
Apr 2021, Scientific Reports, https://www.nature.com/articles/s41598-021-88509-9, https://c19p.org/reanato
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