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HCQ for COVID-19
372 studies from 6,171 scientists
495,620 patients in 54 countries
Statistically significant improvement for mortality, hospitalization, recovery, cases, and viral clearance.
62%, 19% improvement for early and late treatment CI [52-70%], [14-23%]; 36, 246 studies
23% improvement in 8 early treatment RCTs CI [-20-51%]
72% less death in 15 early treatment trials CI [57-81%]
COVID-19 HCQ studies. Dec 2022. c19hcq.org
0 0.5 1 1.5+ All studies 25% With exclusions 37% Mortality 22% Hospitalization 17% RCTs 17% RCTs PrEP 27% RCTs Early 23% RCTs Late 15% Early 62% Early Mortality 72% Early Hosp. 41% PrEP 35% PEP 32% Late 19% FavorsHCQ Favorscontrol
Global HCQ/CQ studies
December 5, 2022
@CovidAnalysis
451 HCQ COVID-19 studies, 353 peer reviewed, 372 comparing treatment and control groups. Late treatment and high dosages may be harmful, while early treatment consistently shows positive results. Negative evaluations typically ignore treatment delay. Some In Vitro evidence suggested therapeutic levels would not be reached, however that was incorrect [Ruiz]. Recent:
Flores-Chavez
Landsteiner de Sampaio Amêndola
Bubenek-Turconi
Sukumar
Fernández-Cruz
Patel
Isnardi.
HCQ/CQ was adopted for early treatment in all or part of 41 countries (57 including non-government medical organizations). Submit updates/corrections.
Nov 26
Covid Analysis (Preprint) (meta analysis) HCQ for COVID-19: real-time meta analysis of 376 studies
Early treatment shows 62% [52‑70%] improvement with pooled effects in the 36 early treatment studies. Results are similar after exclusion based sensitivity analysis and after restriction to peer-reviewed studies. The 15 morta..
Nov 21
Landsteiner de Sampaio Amêndola et al., Journal of Clinical Medicine, doi:10.3390/jcm11226865 (meta analysis) COVID-19 Infection in Rheumatic Patients on Chronic Antimalarial Drugs: A Systematic Review and Meta-Analysis
24% lower mortality [p=0.01] and 20% lower hospitalization [p=0.04]. Systematic review and meta analysis of 20 studies on HCQ use in rheumatic disease patients, showing significantly lower mortality and hospitalization with HCQ prophylaxis.
Nov 17
Bubenek-Turconi et al., European Journal of Anaesthesiology, doi:10.1097/EJA.0000000000001776 Clinical characteristics and factors associated with ICU mortality during the first year of the SARS-Cov-2 pandemic in Romania
22% lower mortality [p=0.01]. Prospective study of 9,058 COVID-19 ICU patients in Romania, showing lower mortality with HCQ treatment.
Nov 14
Sukumar et al., F1000Research, doi:10.12688/f1000research.109023.1 The Frontline War: A Case-control study of risk factors for COVID-19 among health care workers
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 stati..
Oct 26
Patel et al., Seminars in Arthritis and Rheumatism, doi:10.1016/j.semarthrit.2022.152108 Factors Associated with COVID-19 Breakthrough Infection Among Vaccinated Patients with Rheumatic Diseases: A Cohort Study
41% fewer cases [p=0.02]. Retrospective 11,468 vaccinated rheumatic disease patients, showing lower risk of COVID-19 cases with HCQ/CQ (antimalarial) treatment compared with all other treatments, statistically significant for 6 treatments.
Oct 21
Assad, H., Current Issues in Pharmacy and Medical Sciences, doi:10.2478/cipms-2022-0020 Pharmacotherapy prescribing pattern and outcome for hospitalized patients with severe and critical COVID-19
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 13
Gómez et al., Medicina Clínica (English Edition), doi:10.1016/j.medcle.2022.01.020 Mortality risk factors in patients with SARS-CoV-2 infection and atrial fibrillation: Data from the SEMI-COVID-19 registry
36% lower mortality [p<0.0001]. Retrospective 1,799 hospitalized COVID-19 patients with atrial fibrillation in Spain, showing lower mortality with HCQ treatment in unadjusted results.
Oct 6
Isnardi et al., Clinical Rheumatology, doi:10.1007/s10067-022-06393-8 Sociodemographic and clinical factors associated with poor COVID-19 outcomes in patients with rheumatic diseases: data from the SAR-COVID Registry
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 se..
Sep 28
Obrișcă et al., Biomedicines, doi:10.3390/biomedicines10102423 Characteristics of SARS-CoV-2 Infection in an Actively Monitored Cohort of Patients with Lupus Nephritis
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 27
Go et al., Frontiers in Pharmacology, doi:10.3389/fphar.2022.935370 Hydroxychloroquine, azithromycin and methylprednisolone and in hospital survival in severe COVID-19 pneumonia
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 14
Yuan et al., Communications Biology, doi:10.1038/s42003-022-03841-8 (In Vitro) Hydroxychloroquine blocks SARS-CoV-2 entry into the endocytic pathway in mammalian cell culture
In Vitro study showing that HCQ blocks SARS-CoV-2 entry into the endocytic pathway, and that HCQ was more effective with higher cholesterol. Authors also obtained lung samples from adults with chronic obstructive pulmonary disease, findin..
Sep 11
Gentry et al., The American Journal of the Medical Sciences, doi:10.1016/j.amjms.2022.08.006 Development of SARS-CoV-2 infection in patients with rheumatic conditions on hydroxychloroquine monotherapy vs. patients without rheumatic conditions: a retrospective, propensity-matched cohort study
12% lower mortality [p=0.99], 12% lower hospitalization [p=0.81], and 14% more cases [p=0.57]. Updated version of [Gentry] showing no significant difference in outcomes with HCQ use. The previous version is more informative because authors previously analyzed rheumatic disease patients, while they now compare rheumatic disease pati..
Sep 9
Núñez-Gil et al., Anti-Infective Agents, doi:10.2174/2211352520666220514112951 Hydroxychloroquine and Mortality in SARS-Cov-2 Infection; The HOPE- Covid-19 Registry.
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 7
Sahebari et al., Reumatologia/Rheumatology, doi:10.5114/reum.2022.119039 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
56% fewer cases [p=0.02]. Retrospective 512 rheumatic disease patients in Iran, showing lower risk of COVID-19 with HCQ use.
Sep 6
Oku et al., Modern Rheumatology, doi:10.1093/mr/roac104 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
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 1
Flores-Chavez et al., Clinical and Experimental Rheumatology, doi:10.55563/clinexprheumatol/pt3syo SARS-CoV-2 infection in 898 patients with Sjögren’s syndrome: characteristics associated with poor outcomes
Retrospective 898 patients with Sjögren’s disease, showing a lower risk of worse outcomes with HCQ compared to corticosteroids, immunosuppressive agents, and B-cell depleting agents.
Aug 31
Babayigit et al., Frontiers in Medicine, doi:10.3389/fmed.2022.894126 The association of antiviral drugs with COVID-19 morbidity: The retrospective analysis of a nationwide COVID-19 cohort
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 25
Bowen et al., Open Forum Infectious Diseases, doi:10.1093/ofid/ofac436 Reduction in risk of death among patients admitted with COVID-19 between first and second epidemic waves in New York City
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 re..
Aug 16
Loucera et al., medRxiv, doi:10.1101/2022.08.14.22278751 (Preprint) Real-world evidence with a retrospective cohort of 15,968 Andalusian COVID-19 hospitalized patients suggests 21 new effective treatments and one drug that increases death risk
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, aspirin, vitamin D, vitamin C, and budesonide.
Aug 12
Lyashchenko et al., British Journal of Clinical Pharmacology, doi:10.1111/bcp.15489 Systemic Exposure to Hydroxychloroquine and its relationship with outcome in severely ill COVID‐19 patients in New York City
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 9
García-Albéniz et al., European Journal of Epidemiology, doi:10.1007/s10654-022-00891-4 (date from earlier preprint) (meta analysis) Systematic review and meta-analysis of randomized trials of hydroxychloroquine for the prevention of COVID-19
28% fewer cases [p=0.003]. Systematic review and meta-analysis of HCQ prophylaxis RCTs showing a statistically significant reduction in cases for pre-exposure prophylaxis. For PEP trials there were very long treatment delays - in one trial about a third of particip..
Aug 5
Becetti et al., Qatar Medical Journal, doi:10.5339/qmj.2022.37 Prevalence of coronavirus disease 2019 in a multiethnic cohort of patients with autoimmune rheumatic diseases in Qatar
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 signifi..
Aug 5
Polo et al., Clinical Microbiology and Infection, doi:10.1016/j.cmi.2022.07.006 Daily tenofovir disoproxil fumarate/emtricitabine and hydroxychloroquine for pre-exposure prophylaxis of COVID-19: a double-blind placebo controlled randomized trial in healthcare workers
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.
Jul 26
Xu et al., Rapid Communications in Mass Spectrometry, doi:10.1002/rcm.9358 (Dosing) A study of impurities in the repurposed COVID-19 drug hydroxychloroquine sulfate by UHPLC-Q/TOF-MS and LC-SPE-NMR
Analysis of HCQ from two manufacturers showing 9 different impurities, with significantly different concentrations for each manufacturer.
Jul 15
Patel et al., medRxiv, doi:10.1101/2022.07.13.22277606 (Preprint) Factors Associated with COVID-19 Breakthrough Infection in the Pre-Omicron Era Among Vaccinated Patients with Rheumatic Diseases: A Cohort 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 14
Malundo et al., IJID Regions, doi:10.1016/j.ijregi.2022.07.009 Predictors of Mortality among inpatients with COVID-19 Infection in a Tertiary Referral Center in the Philippines
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 11
Yadav et al., Indian Journal of Community Medicine, doi:10.4103/ijcm.ijcm_684_21 Hydroxychloroquine/chloroquine prophylaxis among health-care workers: Was it really preventive? – Evidence from a multicentric cross-sectional 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 3
Raabe et al., medRxiv, doi:10.1101/2022.07.01.22277058 (Preprint) Hydroxychloroquine pre-exposure prophylaxis to prevent SARS-CoV-2 among health care workers at risk for SARS-CoV-2 exposure: A nonrandomized controlled trial
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 h..
Jul 1
Osawa et al., The Journal of Critical Care Medicine, doi:10.2478/jccm-2022-0015 Characteristics and risk factors for mortality in critically ill patients with COVID-19 receiving invasive mechanical ventilation: the experience of a private network in Sao Paulo, Brazil
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..
Jun 29
Nimitvilai et al., Journal of Global Infectious Diseases, doi:10.4103/jgid.jgid_281_21 A randomized controlled trial of combined ivermectin and zinc sulfate versus combined hydroxychloroquine, darunavir/ritonavir, and zinc sulfate among adult patients with asymptomatic or mild coronavirus-19 infection
50% worse viral clearance [p=0.12]. RCT low-risk patients in Thailand comparing HCQ, darunavir/ritonavir, and zinc, with ivermectin and zinc, showing no significant differences. All patients recovered. 65% of patients were asymptomatic at baseline, 26% were PCR- at baseline..
Jun 1
Tirupakuzhi Vijayaraghavan et al., BMJ Open, doi:10.1136/bmjopen-2021-059540 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
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 discont..
May 20
Silva et al., Frontiers in Cellular and Infection Microbiology, doi:10.3389/fcimb.2022.899702 Clinical-Epidemiology Aspect of Inpatients With Moderate or Severe COVID-19 in a Brazilian Macroregion: Disease and Countermeasures
46% higher mortality [p=0.22]. Retrospective 395 hospitalized patients in Brazil, showing higher mortality with HCQ treatment, without statistical significance.
May 16
Gkioulekas et al., Authorea, Inc., doi:10.22541/au.164745391.17821933/v2 (Preprint) Frequentist and Bayesian analysis methods for case series data and application to early outpatient COVID-19 treatment case series of high risk patients
Hybrid statistical framework for evaluating treatment protocols. COVID-19 treatment protocols often use risk stratification, multiple treatments, and customization based on the disease stage and the patient. Authors find strong evidence f..
May 4
Hong et al., PLOS ONE, doi:10.1371/journal.pone.0267645 Use of combined treatment of 3rd-generation cephalosporin, azithromycin and antiviral agents on moderate SARs-CoV-2 patients in South Korea: A retrospective cohort 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 fo..
Apr 22
Satti et al., Cureus, doi:10.7759/cureus.24382 Characteristics and Obstetric Outcomes in Women With Autoimmune Rheumatic Disease During the COVID-19 Pandemic in Qatar
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 17
Faísca et al., Pharmaceutics, doi:10.3390/pharmaceutics14040877 (In Vitro) Enhanced In Vitro Antiviral Activity of Hydroxychloroquine Ionic Liquids against SARS-CoV-2
In Vitro study showing improved antiviral activity with ionic formulations of HCQ.
Apr 16
Roy-García et al., medRxiv, doi:10.1101/2022.04.06.22273531 (Preprint) Efficacy and Safety of Fixed Combination of Hydroxychloroquine with Azithromycin Versus Hydroxychloroquine and Placebo in Patients with Mild COVID-19: Randomized, double blind, Placebo controlled trial
Small early terminated RCT in Mexico with 31 HCQ and 31 control patients, showing higher progression with treatment. There were no hospitalizations in the HCQ and control groups. HCQ patients were older, 38 vs. 32. There were no differenc..
Apr 8
Hafez et al., Antibiotics, doi:10.3390/antibiotics11040498 Antiviral Used among Non-Severe COVID-19 Cases in Relation to Time till Viral Clearance: A Retrospective Cohort 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 6
Walbi et al., Journal of International Medical Research, doi:10.1177/03000605221090363 Effect of chronic hydroxychloroquine use on COVID-19 risk in patients with rheumatoid arthritis and systemic lupus erythematosus: a multicenter retrospective cohort
Retrospective RA/SLE patients in Saudi Arabia. Numbers in this paper are contradictory. Figure 1 and the introduction to the results indicate 304 HCQ users, while Table 1 and later in the results shows 207 (arms switched). The subsequent ..
Apr 2
Delandre et al., Pharmaceuticals, doi:10.3390/ph15040445 (In Vitro) Antiviral Activity of Repurposing Ivermectin against a Panel of 30 Clinical SARS-CoV-2 Strains Belonging to 14 Variants
In Vitro study with 30 COVID-19 strains from 14 variants, showing stronger efficacy with ivermectin compared to CQ and remdesivir, and relatively homogeneous efficacy with ivermectin regardless of strain/variant, in contrast to results fo..
Mar 31
Avezum et al., The Lancet Regional Health - Americas, doi:10.1016/j.lana.2022.100243 Hydroxychloroquine versus placebo in the treatment of non-hospitalised patients with COVID-19 (COPE – Coalition V): A double-blind, multicentre, randomised, controlled trial
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 treat..
Mar 29
MacFadden et al., Open Forum Infectious Diseases, doi:10.1093/ofid/ofac156 Screening Large Population Health Databases for Potential COVID-19 Therapeutics: A Pharmacopeia-Wide Association Study (PWAS) of Commonly Prescribed Medications
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 23
AlQahtani et al., Scientific Reports, doi:10.1038/s41598-022-08794-w Randomized controlled trial of favipiravir, hydroxychloroquine, and standard care in patients with mild/moderate COVID-19 disease
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 21
Oztas et al., Journal of Medical Virology, doi:10.1002/jmv.27731 Frequency and Severity of COVID-19 in Patients with Various Rheumatic Diseases Treated Regularly with Colchicine or Hydroxychloroquine
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 19
Ragonnet et al., Future Pharmacology, doi:10.3390/futurepharmacol2010007 (Dosing) Drug Repositioning in Intensive Care Patients and Pharmacokinetic Variability: The Illustration of Hydroxychloroquine
Comparison of two HCQ dosing regimens, showing high inter-individual variability of HCQ concentrations (as in [Ruiz]), and significantly better plasma concentrations for the dosing regimen including a loading dose.
Mar 18
Ebongue et al., Travel Medicine and Infectious Disease, doi:10.1016/j.tmaid.2022.102292 Factors predicting in-hospital all-cause mortality in COVID 19 patients at the Laquintinie Hospital Douala, Cameroon
43% lower mortality [p=0.04]. Retrospective 580 hospitalized COVID+ patients in Cameroon, showing lower mortality with HCQ+AZ treatment.
Mar 17
Uyaroğlu et al., Acta Medica, doi:10.32552/2022.ActaMedica.719 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
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 11
Salehi et al., Research Square, doi:10.21203/rs.3.rs-1362678/v1 (Preprint) Risk factors of death in mechanically ventilated COVID-19 patients: a retrospective multi-center 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 10
Azaña Gómez et al., Medicina Clínica, doi:10.1016/j.medcli.2022.01.008 Mortality risk factors in patients with SARS-CoV-2 infection and atrial fibrillation: Data from the SEMI-COVID-19 registry
36% lower mortality [p<0.0001]. Retrospective 1,816 COVID-19 patients with atrial fibrillation in Spain, showing lower mortality with HCQ treatment.
Mar 4
Del Amo, J., medRxiv, doi:10.1101/2022.03.02.22271710 (Preprint) Daily tenofovir disoproxil fumarate/emtricitabine and hydroxychloroquine for pre-exposure prophylaxis of COVID-19: a double-blind placebo controlled randomized trial in healthcare workers
27% fewer cases [p=0.31]. PrEP RCT with 231 HCQ, 220 TDF/FTC+HCQ, 233 TDF/FTC, and 223 placebo healthcare workers in Spain, Bolivia, and Venezuela, showing lower risk of symptomatic COVID-19 in all treatment arms, without statistical significance. Only 907 of the ..
Mar 3
Tsanovska et al., Infectious Disorders - Drug Targets, doi:10.2174/1871526522666220303121209 Hydroxychloroquine (HCQ) treatment for hospitalized patients with COVID- 19.
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 2
Soto et al., PLOS ONE, doi:10.1371/journal.pone.0264789 Mortality and associated risk factors in patients hospitalized due to COVID-19 in a Peruvian reference hospital
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..
Feb 26
Rouamba et al., International Journal of Infectious Diseases, doi:10.1016/j.ijid.2022.02.034 Assessment of Recovery Time, Worsening and Death, among COVID-19 inpatients and outpatients, under treatment with Hydroxychloroquine or Chloroquine plus Azithromycin Combination in Burkina Faso
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 23
Opdam et al., Clinical Pharmacology & Therapeutics, doi:10.1002/cpt.2551 Identification of Risk Factors for COVID‐19 Hospitalization in Patients with Anti‐Rheumatic Drugs: Results from a Multicenter Nested Case Control 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 18
Hall et al., The Annals of Thoracic Surgery, doi:10.1016/j.athoracsur.2022.01.043 Multi-institutional Analysis of 505 COVID-19 Patients Supported with ECMO: Predictors of Survival
11% lower mortality [p=0.31]. Retrospective 505 ECMO patients showing no significant difference in mortality in unadjusted results.
Feb 16
Ugarte-Gil et al., Annals of the Rheumatic Diseases, doi:10.1136/annrheumdis-2021-221636 Characteristics associated with poor COVID-19 outcomes in individuals with systemic lupus erythematosus: data from the COVID-19 Global Rheumatology Alliance
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 13
Beaumont et al., Infectious Diseases Now, doi:10.1016/j.idnow.2022.02.001 Factors associated with hospital admission and adverse outcome for COVID-19: role of social factors and medical care
14% lower combined mortality/intubation [p=0.55]. Retrospective 296 hospitalized patients in France, showing no significant difference with HCQ treatment.
Feb 3
Albanghali et al., Journal of Infection and Public Health, doi:10.1016/j.jiph.2022.02.001 Clinical Characteristics and Treatment Outcomes of Mild to Moderate Covid-19 Patients in Saudi Arabia: A Single Centre 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.
Jan 31
Fernández-Cruz et al., Clinical Infection in Practice, doi:10.1016/j.clinpr.2022.100137 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
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 31
Omma et al., The Journal of Infection in Developing Countries, doi:10.3855/jidc.14933 Hydroxychloroquine shortened hospital stay and reduced intensive care unit admissions in hospitalized COVID-19 patients
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 baseli..
Jan 27
Strangfeld et al., Annals of the Rheumatic Diseases, doi:10.1136/annrheumdis-2020-219498 Factors associated with COVID-19-related death in people with rheumatic diseases: results from the COVID-19 Global Rheumatology Alliance physician-reported registry
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 23
Erden et al., Bratislava Medical Journal, doi:10.4149/BLL_2022_018 COVID-19 outcomes in patients with antiphospholipid syndrome: a retrospective cohort 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 21
Lavilla Olleros et al., PLOS ONE, doi:10.1371/journal.pone.0261711 Use of glucocorticoids megadoses in SARS-CoV-2 infection in a spanish registry: SEMI-COVID-19
36% lower mortality [p<0.0001]. Retrospective 14,921 hospitalized patients in Spain, showing lower mortality with HCQ treatment.
Jan 20
Alwafi et al., Cureus, doi:10.7759/cureus.21442 Negative Nasopharyngeal SARS-CoV-2 PCR Conversion in Response to Different Therapeutic Interventions
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 13
Tu et al., Infectious Diseases & Immunity, doi:10.1097/ID9.0000000000000037 Risk Factors for Severity and Mortality in Adult Patients Confirmed with COVID-19 in Sierra Leone: A Retrospective 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 13
Tyson et al., Preprint (Preprint) Low Rates of Hospitalization and Death in 4,376 COVID-19 Patients Given Early Ambulatory Medical and Supportive Care. A Case Series and Observational Study.
100% lower mortality [p<0.0001] and 100% lower hospitalization [p<0.0001]. Retrospective 4,376 patients with mild/moderate COVID-19 in the USA treated with multiple medications including HCQ/ivermectin, favipiravir, vitamin C, D, quercetin, zinc, mAbs, budesonide, dexamethasone, prednisone, and colchicine (exact..
Jan 11
AbdelGhaffar et al., PLOS ONE, doi:10.1371/journal.pone.0262348 Prediction of mortality in hospitalized Egyptian patients with Coronavirus disease-2019: A multicenter retrospective 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 7
Juneja et al., Journal of Basic and Clinical Physiology and Pharmacology, doi:10.1515/jbcpp-2021-0221 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
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.
Dec 23
2021
McKinnon et al., International Journal of Infectious Diseases, doi:10.1016/j.ijid.2021.12.343 Safety and Tolerability of Hydroxychloroquine in healthcare workers and first responders for the prevention of COVID-19: WHIP COVID-19 Study
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..
Dec 4
2021
Rao et al., Expert Review of Anti-infective Therapy, doi:10.1080/14787210.2022.2015326 Hydroxychloroquine as pre-exposure prophylaxis against COVID-19 infection among healthcare workers: a prospective cohort 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 informat..
Nov 26
2021
Ferreira et al., Revista da Associação Médica Brasileira, doi:10.1590/1806-9282.20210661 Outcomes associated with Hydroxychloroquine and Ivermectin in hospitalized patients with COVID-19: a single-center experience
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 indicate that they do not know when medication was ..
Nov 23
2021
Calderón et al., PAMJ - Clinical Medicine, doi:10.11604/pamj-cm.2021.7.15.30981 Treatment with hydroxychloroquine vs nitazoxanide in patients with COVID-19: brief report
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 re..
Nov 23
2021
Ahmed et al., BioMed Research International, doi:10.1155/2021/1676914 Factors Affecting the Incidence, Progression, and Severity of COVID-19 in Type 1 Diabetes Mellitus
99% fewer cases [p=0.08]. Retrospective type 1 diabetes patients in Saudi Arabia showing reduced risk of cases with HCQ prophylaxis.
Nov 17
2021
Samajdar et al., Journal of the Association of Physicians India, 69:11 Ivermectin and Hydroxychloroquine for Chemo-Prophylaxis of COVID-19: A Questionnaire Survey of Perception and Prescribing Practice of Physicians vis-a-vis Outcomes
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 ar..
Nov 12
2021
Schmidt et al., JAMA Network Open, doi:10.1001/jamanetworkopen.2021.34330 Association Between Androgen Deprivation Therapy and Mortality Among Patients With Prostate Cancer and COVID-19
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 11
2021
Cortez et al., Western Pacific Surveillance and Response Journal, doi:10.5365/wpsar.2021.12.4.852 Clinical characteristics and outcomes of COVID-19 patients in a tertiary hospital in Baguio City, Philippines
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 5
2021
Chechter et al., medRxiv, doi:10.1101/2021.11.05.21265569 (Preprint) Evaluation of patients treated by telemedicine in the COVID-19 pandemic by a private clinic in Sao Paulo, Brazil: A non-randomized clinical trial preliminary 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 improv..
Nov 2
2021
Sarhan et al., Journal of Infection and Public Health, doi:10.1016/j.jiph.2021.10.024 Efficacy of the early treatment with tocilizumab-hydroxychloroquine and tocilizumab-remdesivir in severe COVID-19 Patients
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.
Oct 28
2021
Shousha et al., World Journal of Gastroenterology, doi:10.3748/wjg.v27.i40.6951 Hepatic and gastrointestinal disturbances in Egyptian patients infected with coronavirus disease 2019: A multicentre cohort study
12% lower mortality [p=0.87]. Retrospective 547 hospitalized COVID+ patients in Egypt, showing no significant differences with CQ/HCQ treatment in unadjusted analysis. Treatments were applied according to patient conditions, demographics, and comorbidities as per the ..
Oct 25
2021
Guglielmetti et al., Scientific Reports, doi:10.1038/s41598-021-00243-4 Treatment for COVID-19—a cohort study from Northern Italy
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 6
2021
Belmont et al., ClinicalTrials.gov, NCT04354870 (Preprint) COVID-19 PrEP HCW HCQ 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 5
2021
Atipornwanich et al., SSRN Electronic Journal, doi:10.2139/ssrn.3936499 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)
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..
Oct 1
2021
Fung et al., PLoS ONE, doi:10.1371/journal.pone.0266922 (date from earlier preprint) Effect of common maintenance drugs on the risk and severity of COVID-19 in elderly patients
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 sh..
Oct 1
2021
Babalola et al., Journal of Infectious Diseases and Epidemiology, doi:10.23937/2474-3658/1510233 (date from earlier preprint) A Randomized Controlled Trial of Ivermectin Monotherapy Versus Hydroxychloroquine, Ivermectin, and Azithromycin Combination Therapy in Covid-19 Patients in Nigeria
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 30
2021
Menardi et al., PharmAdvances, doi:10.36118/pharmadvances.2021.15 A retrospective analysis on pharmacological approaches to COVID-19 patients in an Italian hub hospital during the early phase of the pandemic
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 15
2021
Uygen et al., Northern Clinics of Istanbul, doi:10.14744/nci.2021.65471 Effect of Hydroxychloroquine Use on the Length Of Hospital Stay in Children Diagnosed With Covid 19
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 15
2021
Çivriz Bozdağ et al., Turk. J. Haematol., doi:10.4274/tjh.galenos.2021.2021.0287 Clinical Characteristics and Outcome of COVID-19 in Turkish Hematological Malignancy Patients
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 significan..
Sep 14
2021
Alotaibi et al., International Journal of General Medicine, 2021:14 Effectiveness and Safety of Favipiravir Compared to Hydroxychloroquine for Management of Covid-19: A Retrospective 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 subjec..
Sep 14
2021
Agarwal et al., medRxiv, doi:10.1101/2021.09.13.21262971 (Preprint) Low dose hydroxychloroquine prophylaxis for COVID-19 - a prospective 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 14
2021
Accinelli et al., Travel Medicine and Infectious Disease, doi:10.1016/j.tmaid.2021.102163 Hydroxychloroquine / azithromycin in COVID-19: The association between time to treatment and case fatality rate
Retrospective 1,265 outpatients in Peru treated with HCQ+AZ showing mortality associated with treatment delay. Mortality was six times lower than the national average.
Sep 9
2021
Sawanpanyalert et al., Southeast Asian Journal of Tropical Medicine and Public Health, 52:4 Assessment of outcomes following implementation of antiviral treatment guidelines for COVID-19 during the first wave in Thailand
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 low..
Sep 1
2021
Karruli et al., Microbial Drug Resistance, doi:10.1089/mdr.2020.0489 Multidrug-Resistant Infections and Outcome of Critically Ill Patients with Coronavirus Disease 2019: A Single Center Experience
5% lower mortality [p=1]. Retrospective 32 ICU patients, showing no significant difference with HCQ treatment in unadjusted results.
Aug 27
2021
Cordtz et al., Journal of Clinical Medicine, doi:10.3390/jcm10173842 Incidence of COVID-19 Hospitalisation in Patients with Systemic Lupus Erythematosus: A Nationwide Cohort Study from Denmark
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 25
2021
Rodrigues et al., International Journal of Antimicrobial Agents, doi:10.1016/j.ijantimicag.2021.106428 Hydroxychloroquine plus azithromycin early treatment of mild COVID-19 in outpatient setting: a randomized, double-blinded, placebo-controlled clinical trial evaluating viral clearance
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 25
2021
Naggie et al., medRxiv, doi:10.1101/2021.08.19.21262275 (Preprint) Hydroxychloroquine for pre-exposure prophylaxis of COVID-19 in health care workers: a randomized, multicenter, placebo-controlled trial (HERO-HCQ)
24% fewer symptomatic cases [p=0.18]. RCT 1,360 healthcare workers in the USA showing OR 0.75 [0.49-1.15] for confirmed or suspected COVID-19 clinical infection by day 30. There were no significant safety issues. Authors note that pooling the results with the COVID PREP study..
Aug 24
2021
Patil et al., Research Square, doi:10.21203/rs.3.rs-805748/v1 (Preprint) A Prospective Longitudinal Study Evaluating The Influence of Immunosuppressives and Other Factors On COVID-19 in Autoimmune Rheumatic Diseases
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..
Aug 16
2021
Eldeen et al., Microbes and Infectious Diseases, doi:10.21608/mid.2021.85877.1177 Comparative study between the therapeutic effect of remdesivir versus hydroxychloroquine in COVID-19 hospitalized patients
Small study comparing 25 HCQ and 25 remdesivir hospitalized patients, reporting faster viral clearance with remdesivir. The article proof is missing the results for the HCQ group. Confounding by time is likely - remdesivir patients were a..
Aug 14
2021
Tai et al., Pharmaceutics, doi:10.3390/pharmaceutics13081260 Nebulised Isotonic Hydroxychloroquine Aerosols for Potential Treatment of COVID-19
Analysis of HCQ solutions suitable for nebulization for COVID-19.
Aug 10
2021
Shabani et al., Pulmonary Pharmacology & Therapeutics, doi:10.1016/j.pupt.2021.102069 Evaluation of the Prophylactic Effect of Hydroxychloroquine on People in Close-Contact with Patients with Covid-19
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 5
2021
Stricker et al., Journal of Infection and Public Health, doi:10.1016/j.jiph.2021.08.001 (meta analysis) Hydroxychloroquine Pre-Exposure Prophylaxis for COVID-19 in Healthcare Workers from India: A Meta-Analysis
75% lower mortality [p<0.0001]. Meta analysis of 11 HCQ PrEP studies in India covering 7,616 healthcare workers, showing significantly lower cases with treatment.
Aug 4
2021
Özuygur Ermiş et al., Turkish Journal of Medical Sciences, doi:10.3906/sag-2009-64 The Efficacy of Hydroxychloroquine and Azithromycin Combination Therapy on Hospital Mortality in COVID 19 Pneumonia Patients
Retrospective 370 hospitalized patients, 222 receiving HCQ+AZ and 148 receiving HCQ, showing mortality OR 0.61 [0.23-1.59], p = 0.31 for the addition of AZ.
Aug 4
2021
Bhatt et al., medRxiv, doi:10.1101/2021.08.02.21260750 (Preprint) Hydroxychloroquine Prophylaxis against Coronavirus Disease-19: Practice Outcomes among Health-Care Workers
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..
Aug 4
2021
Alghamdi et al., Saudi Pharmaceutical Journal, doi:10.1016/j.jsps.2021.08.008 Clinical characteristics and treatment outcomes of severe (ICU) COVID-19 patients in Saudi Arabia: A single centre study
39% higher mortality [p=0.52]. Retrospective 171 ICU patients in Saudi Arabia showing no significant difference for HCQ treatment in unadjusted results.
Jul 31
2021
Barra et al., medRxiv, doi:10.1101/2021.07.30.21261220 (Preprint) COVID-19 in hospitalized patients in 4 hospitals in San Isidro, Buenos Aires, Argentina
11% lower mortality [p=1]. Retrospective 668 hospitalized patients in Argentina, 18 treated with HCQ, not showing a significant difference in unadjusted results.
Jul 29
2021
Sobngwi et al., medRxiv, doi:10.1101/2021.07.25.21260838 (Preprint) Doxycycline is a safe alternative to Hydroxychloroquine + Azithromycin to prevent clinical worsening and hospitalization in mild COVID-19 patients: An open label randomized clinical trial (DOXYCOV)
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, but without statistical significance. ..
Jul 20
2021
Küçükakkaş et al., Research Square, doi:10.21203/rs.3.rs-43812/v1 (Preprint) The effect of hydroxychloroquine against SARS-CoV-2 infection in rheumatoid arthritis patients
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 r..
Jul 16
2021
Alhamlan et al., medRxiv, doi:10.1101/2021.07.13.21260428 (Preprint) Epidemiology and Clinical Characteristics in Individuals with Confirmed SARS-CoV-2 Infection During the Early COVID-19 Pandemic in Saudi Arabia
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 lopinavi..
Jul 13
2021
Barrat-Due et al., Annals of Internal Medicine, doi:10.7326/M21-0653 Evaluation of the Effects of Remdesivir and Hydroxychloroquine on Viral Clearance in COVID-19
120% higher mortality [p=0.35]. Small RCT in Norway with 52 HCQ and 42 remdesivir patients, showing no significant differences with treatment. Add-on trial to WHO Solidarity. NCT04321616.
Jul 13
2021
Tamura et al., Diabetology & Metabolic Syndrome, doi:10.1186/s13098-021-00695-8 Outcome and death risk of diabetes patients with Covid-19 receiving pre-hospital and in-hospital metformin therapies
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, a..
Jul 12
2021
Arabi et al., Intensive Care Medicine Lopinavir-ritonavir and hydroxychloroquine for critically ill patients with COVID-19: REMAP-CAP randomized controlled trial
44% higher mortality [p=0.01]. Very late stage RCT with 50 ICU patients treated with HCQ, 255 lopinavir-ritonavir patients, and 27 combined therapy patients, showing higher mortality with all treatments.
Jul 10
2021
Roger et al., Anaesthesia Critical Care & Pain Medicine, doi:10.1016/j.accpm.2021.100931 French Multicentre Observational Study on SARS-CoV-2 infections Intensive care initial management: the FRENCH CORONA 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, w..
Jul 6
2021
Jacobs et al., The Annals of Thoracic Surgery, doi:10.1016/j.athoracsur.2021.06.026 Multi-institutional Analysis of 200 COVID-19 Patients treated with ECMO:Outcomes and Trends
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..
Jul 1
2021
Shaw et al., Journal of Drugs in Dermatology, doi:10.36849/JDD.5843 COVID-19 in Individuals Treated With Long-Term Hydroxychloroquine: A Propensity Score-Matched Analysis of Cicatricial Alopecia Patients
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 30
2021
Taieb et al., J. Clin. Med. 2021, doi:10.3390/jcm10132954 Hydroxychloroquine and Azithromycin Treatment of Hospitalized Patients Infected with SARS-CoV-2 in Senegal from March to October 2020
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 24
2021
Gerlovin et al., American Journal of Epidemiology, doi:10.1093/aje/kwab183 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
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 21
2021
Yadav et al., Research Square, doi:10.21203/rs.3.rs-628277/v1 (Preprint) Repurposing the Combination Drug of Favipiravir, Hydroxychloroquine and Oseltamivir as a Potential Inhibitor Against SARS-CoV-2: A Computational Study
In Silico study showing stronger inhibition of SAR-CoV-2 for HCQ+favipiravir+oseltamivir compared to any of these alone or combinations of two of these drugs.
Jun 18
2021
Schwartz et al., CMAJ Open, doi:10.9778/cmajo.20210069 Assessing the efficacy and safety of hydroxychloroquine as outpatient treatment of COVID-19: a randomized controlled trial
133% higher ICU admission [p=1] and 533% higher hospitalization [p=0.57]. Small early terminated late treatment RCT not showing 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..
Jun 18
2021
Purwati et al., PLOS One, doi:10.1371/journal.pone.0252302 (In Vitro) An in vitro study of dual drug combinations of anti-viral agents, antibiotics, and/or hydroxychloroquine against the SARS-CoV-2 virus isolated from hospitalized patients in Surabaya, Indonesia
In Vitro study of combinations of drugs showing antiviral efficacy of HCQ alone and in combination with AZ, favipiravir, and doxycycline. No high levels of cytotoxicity were observed, and authors conclude that using a combination of drugs..
Jun 11
2021
Turrini et al., Vaccines, 10.3390/vaccines9060640 Clinical Course and Risk Factors for In-Hospital Mortality of 205 Patients with SARS-CoV-2 Pneumonia in Como, Lombardy Region, Italy
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 9
2021
Saib et al., PLOS ONE, doi:10.1371/journal.pone.0252388 Lack of efficacy of hydroxychloroquine and azithromycin in patients hospitalized for COVID-19 pneumonia: A retrospective 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 8
2021
Singh et al., medRxiv, doi:0.1101/2021.06.06.21258091 (Preprint) Safety and efficacy of antiviral therapy alone or in combination in COVID-19 - a randomized controlled trial (SEV COVID Trial)
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 ..
Jun 7
2021
Badyal et al., Journal of the Association of Physicians of India, Volume 69, June 2021 Hydroxychloroquine for SARS CoV2 Prophylaxis in Healthcare Workers – A Multicentric Cohort Study Assessing Effectiveness and Safety
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 4
2021
Lagier et al., Therapeutics and Clinical Risk Management, doi:10.2147/TCRM.S364022 Outcomes of 2,111 COVID-19 hospitalised patients treated with 2 hydroxychloroquine/azithromycin and other regimens in Marseille, France: a 3 monocentric retrospective analysis
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 4
2021
Byakika-Kibwika et al., Research Square, doi:10.21203/rs.3.rs-506195/v1 (Preprint) Safety and Efficacy of Hydroxychloroquine for Treatment of Non-Severe COVID-19 in Adults in Uganda: A Randomized Open Label Phase II Clinical Trial
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 treatm..
Jun 3
2021
Sivapalan et al., European Respiratory Journal, doi:10.1183/13993003.00752-2021 Azithromycin and hydroxychloroquine in hospitalised patients with confirmed COVID-19–a randomised double-blinded placebo-controlled trial
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. NCT04322396 ProPAC-COVID. NNF20SA0062834.
Jun 1
2021
Korkmaz et al., Authorea, doi:10.22541/au.162257516.68665404/v1 (Preprint) The effect of Hydroxychloroquine use due to rheumatic disease on the risk of Covid-19 infection and its course
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.
Jun 1
2021
Kamstrup et al., International Journal of Infectious Diseases, doi:10.1016/j.ijid.2021.05.076 Hydroxychloroquine as a primary prophylactic agent against sars-cov-2 infection: a cohort 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 exa..
May 31
2021
Ramírez-García et al., Archivos de Medicina Universitaria Hydroxychloroquine and Tocilizumab in the Treatment of COVID-19: A Longitudinal Observational 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 31
2021
Smith et al., medRxiv, doi:10.1101/2021.05.28.21258012 (Preprint) Observational Study on 255 Mechanically Ventilated Covid Patients at the Beginning of the USA Pandemic
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 immorta..
May 29
2021
Ali et al., Journal of Pharmaceutical Research International, doi:10.9734/jpri/2020/v32i830468 (Dosing) Optimizing the Use of Hydroxychloroquine in the Management of COVID-19 Given Its Pharmacological Profile
Review of the mechanisms of action, pharmacokinetics and toxicity of HCQ, recommending use as early as possible with a loading dose in 3-4 divided doses to minimize toxicity, and daily maintenance divided into two doses, continued until r..
May 27
2021
Million et al., Reviews in Cardiovascular Medicine, doi:10.31083/j.rcm2203116 (date from earlier preprint) Early Treatment with Hydroxychloroquine and Azithromycin in 10,429 COVID-19 Outpatients: A Monocentric Retrospective Cohort 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 17
2021
Syed et al., Cureus, doi:10.7759/cureus.20572 (date from earlier preprint) Pre-exposure Prophylaxis With Various Doses of Hydroxychloroquine Among Healthcare Personnel With High-Risk Exposure to COVID-19: A Randomized Controlled Trial
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 "re..
May 16
2021
Rojas-Serrano et al., medRxiv, doi:10.1101/2021.05.14.21257059 (Preprint) Hydroxychloroquine For Prophylaxis Of COVID-19 In Health Workers: A Randomized Clinical Trial
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. NCT04318015. If the trial is continued and the same event rate is observed, statistical significance will be reached afte..
May 12
2021
Drancourt et al., Viruses, doi:10.3390/v13050890 SARS-CoV-2 Persistent Viral Shedding in the Context of Hydroxychloroquine-Azithromycin Treatment
Retrospective 3,737 patients in France, showing lower risk of persistent viral shedding with HCQ+AZ treatment.
May 10
2021
Sammartino et al., PLOS One, doi:10.1371/journal.pone.0251262 Predictors for inpatient mortality during the first wave of the SARS-CoV-2 pandemic: A retrospective analysis
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 ..
May 8
2021
Vigbedor et al., Journal of Applied Pharmaceutical Science, doi:10.7324/JAPS.2021.110825 (Review) Review of four major biomolecular target sites for COVID-19 and possible inhibitors as treatment interventions
Review of major target sites in SARS-CoV-2 and the host organism along with potential inhibitors.
May 1
2021
De Rosa et al., J. Clin. Med., doi:10.3390/jcm10091951 Risk Factors for Mortality in COVID-19 Hospitalized Patients in Piedmont, Italy: Results from the Multicenter, Regional, CORACLE Registry
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..
Apr 30
2021
Çiyiltepe et al., South. Clin. Ist. Euras., doi:10.14744/scie.2021.89847 The Effect of Pre-admission Hydroxychloroquine Treatment on COVID-19-Related Intensive Care Follow-up in Geriatric Patients
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..
Apr 30
2021
Bosaeed et al., Infect. Dis. Ther., doi:10.1007/s40121-021-00496-6 Favipiravir and Hydroxychloroquine Combination Therapy in Patients with Moderate to Severe COVID19 (FACCT Trial): An Open-Label, Multicenter, Randomized, Controlled Trial
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 e..
Apr 29
2021
Haji Aghajani et al., Journal of Medical Virology, doi:10.1002/jmv.27053 Decreased in-hospital mortality associated with aspirin administration in hospitalized patients due to severe COVID-19
19% lower mortality [p=0.09]. Retrospective 991 hospitalized patients in Iran, showing lower mortality with HCQ, not reaching statistical significance.
Apr 29
2021
Aghajani et al., Journal of Medical Virology, doi:10.1002/jmv.27053 Decreased In-Hospital Mortality Associated with Aspirin Administration in Hospitalized Patients Due to Severe COVID-19
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 28
2021
Kokturk et al., Respiratory Medicine, doi:10.1016/j.rmed.2021.106433 The predictors of COVID-19 mortality in a nationwide cohort of Turkish patients
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 27
2021
Réa-Neto et al., Scientific Reports, doi:10.1038/s41598-021-88509-9 An open-label randomized controlled trial evaluating the efficacy of chloroquine/hydroxychloroquine in severe COVID-19 patients
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 26
2021
Mohandas et al., Clinical review of COVID-19 patients presenting to a quaternary care private hospital in South India: A retrospective 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 treatm..
Apr 24
2021
Corradini et al., Internal and Emergency Medicine, doi:10.1007/s11739-021-02742-8 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)
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 23
2021
Toya et al., SSRN (Preprint) A Cross-Country Analysis of the Determinants of COVID-19 Fatalities
Country based analysis finding lower mortality with the use of HCQ.
Apr 22
2021
Reis et al., JAMA Network Open, doi:10.1001/jamanetworkopen.2021.6468 Effect of Early Treatment With Hydroxychloroquine or Lopinavir and Ritonavir on Risk of Hospitalization Among Patients With COVID-19 The TOGETHER Randomized Clinical Trial
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 bei..
Apr 15
2021
Alzahrani et al., Rheumatology International , doi:10.1007/s00296-021-04857-9 Clinical characteristics and outcome of COVID-19 in patients with rheumatic diseases
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 15
2021
Alegiani et al., Rheumatology, doi:10.1093/rheumatology/keab348 Risk of COVID-19 hospitalization and mortality in rheumatic patients treated with hydroxychloroquine or other conventional DMARDs in Italy
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 signif..
Apr 14
2021
Seet et al., International Journal of Infectious Diseases, doi:10.1016/j.ijid.2021.04.035 Positive impact of oral hydroxychloroquine and povidone-iodine throat spray for COVID-19 prophylaxis: an open-label randomized trial
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 ..
Apr 8
2021
Gadhiya et al., BMJ Open, doi:10.1136/bmjopen-2020-042549 Clinical characteristics of hospitalised patients with COVID-19 and the impact on mortality: a single-network, retrospective cohort study from Pennsylvania state
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 fo..
Apr 7
2021
Mulhem et al., BMJ Open, doi:10.1136/bmjopen-2020-042042 3219 hospitalised patients with COVID-19 in Southeast Michigan: a retrospective case cohort 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..
Apr 6
2021
Mokhtari et al., International Immunopharmacology, doi:10.1016/j.intimp.2021.107636 Clinical outcomes of patients with mild COVID-19 following treatment with hydroxychloroquine in an outpatient setting
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 5
2021
Edington et al., European Journal of Internal Medicine, doi:10.1016/j.ejim.2021.03.028 Safety of treatment with chloroquine and hydroxychloroquine: A ten-year systematic review and meta-analysis
Safety analysis of CQ and HCQ covering 46 RCTs with 23,132 patients, showing no mortality attributed to CQ/HCQ. Authors conclude that the data reinforces that CQ and HCQ have a good safety profile though caution is advised when using high..
Mar 31
2021
Alghamdi et al., Antibiotics, doi:10.3390/antibiotics10040365 Clinical Efficacy of Hydroxychloroquine in Patients with COVID-19: Findings from an Observational Comparative Study in Saudi Arabia
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 26
2021
Faruqui et al., Indian J. Med. Res., doi:10.4103/ijmr.IJMR_2294_20 Safety of hydroxychloroquine in healthcare workers for COVID-19 prophylaxis
Retrospective 1303 health care workers finding that HCQ prophylaxis was well tolerated. 20% reported an adverse event, mostly gastrointestinal. 1.5% received treatment for adverse effects, with none requiring hospitalization.
Mar 24
2021
Dev et al., Transactions of The Royal Society of Tropical Medicine and Hygiene, doi:10.1093/trstmh/trab047 Risk factors and frequency of COVID-19 among healthcare workers at a tertiary care centre in India: a case–control 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 m..
Mar 23
2021
Barry et al., International Journal of Infectious Diseases, doi:10.1016/j.ijid.2021.03.058 Clinical Characteristics and Outcomes of Hospitalized COVID-19 Patients in a MERS-CoV Referral Hospital during the Peak of the Pandemic
99% lower mortality [p=0.6]. 605 hospitalized patients in Saudi Arabia showing no mortality with HCQ (only 6 patients received HCQ).
Mar 17
2021
Stewart et al., PLoS ONE, doi:10.1371/journal.pone.0248128 COVID-19 Evidence Accelerator: A parallel analysis to describe the use of Hydroxychloroquine with or without Azithromycin among hospitalized COVID-19 patients
18% higher mortality [p=0.27] and 29% higher ventilation [p=0.09]. Collection of seven retrospective database analyses in the USA, showing higher mortality with treatment (not statistically significant). Results contradict strong evidence from the RECOVERY/SOLIDARITY trials, suggesting substantial confou..
Mar 17
2021
Dang et al., bioRxiv, doi:10.1101/2021.03.16.435741 (Preprint) (In Vitro) Structural basis of anti-SARS-CoV-2 activity of hydroxychloroquine: specific binding to NTD/CTD and disruption of LLPS of N protein
Microscopy/spectroscopy study showing that HCQ binds to both N-terminal domain and C-terminal domain of SARS-CoV-2 nucleocapsid protein to inhibit their interactions with nucleic acids and disrupt NA-induced liquid-liquid phase separation..
Mar 12
2021
Roy et al., medRxiv, doi:10.1101/2021.03.08.21252883 (Preprint) Outcome of Different Therapeutic Interventions in Mild COVID-19 Patients in a Single OPD Clinic of West Bengal: A Retrospective 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 ..
Mar 9
2021
Vivanco-Hidalgo et al., Eurosurveillance, doi:/10.2807/1560-7917.ES.2021.26.9.2001202 Incidence of COVID-19 in patients exposed to chloroquine and hydroxychloroquine: results from a population-based prospective cohort in Catalonia, Spain, 2020
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 fo..
Mar 8
2021
Martin-Vicente et al., medRxiv, doi:10.1101/2021.03.08.21253121 (Preprint) 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
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 4
2021
Salvador et al., Cureus, doi:10.7759/cureus.13687 Clinical Features and Prognostic Factors of 245 Portuguese Patients Hospitalized With COVID-19
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 2
2021
Pham et al., Rheumatology Advances in Practice, 10.1093/rap/rkab014 Failure of chronic hydroxychloroquine in preventing severe complications of COVID-19 in patients with rheumatic diseases
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 mention..
Feb 28
2021
Thakar et al., Indian J. Med. Res., doi:10.4103/ijmr.IJMR_3665_20 Chloroquine nasal drops in asymptomatic & mild COVID-19: An exploratory randomized clinical trial
Small RCT for CQ nasal drops suggesting efficacy in preventing infection, while no significant difference was seen for patients that already had mild COVID-19.
Feb 28
2021
Bhandari et al., International Journal of Medicine and Public Health, doi:10.5530/ijmedph.2021.1.4 A Preventive Study on Hydroxychloroquine Prophylaxis against COVID-19 in Health Care Workers at a Tertiary Care Center in North India
Retrospective 4,239 healthcare workers using HCQ prophylaxis showing no mortality, 8 mild symptomatic cases, and 85 asymptomatic cases, with the cases occuring mostly in the first week.
Feb 26
2021
Amaravadi et al., medRxiv, doi:10.1101/2021.02.22.21252228 (Preprint) Hydroxychloroquine for SARS-CoV-2 positive patients quarantined at home: The first interim analysis of a remotely conducted randomized clinical trial
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 prot..
Feb 26
2021
Tanriverdi et al., Turkish Journal of Medical Sciences, doi:doi:10.3906/sag-2005-82 Hydroxychloroquine plus azithromycin and early hospital admission are beneficial in COVID-19 patients: Turkish experience with real-life data
Retrospective 83 hospitalized patients in Turkey confirming that earlier treatment is better, and showing that the addition of AZ to HCQ reduced hospitalization time.
Feb 26
2021
Giraud-Gatineau et al., Research Square, doi:rs.3.rs-251817/v1 (Preprint) The Need for Early Management in Patients With COVID-19
Review of early treatment of COVID-19 at IHU Méditerranée Infection in France, including HCQ+AZ treatment, comparing outcomes to those for all of France. Age-standardized mortality was lower with early treatment for all periods of the epi..
Feb 23
2021
Beltran Gonzalez et al., Infectious Disease Reports, doi:10.3390/idr14020020 (date from earlier preprint) Efficacy and Safety of Ivermectin and Hydroxychloroquine in Patients with Severe COVID-19: A Randomized Controlled Trial
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 20
2021
Bae et al., Viruses 2021, doi:10.3390/v13020329 Recent Hydroxychloroquine Use Is Not Significantly Associated with Positive PCR Results for SARS-CoV-2: A Nationwide Observational Study in South Korea
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 19
2021
Lamback et al., The Brazilian Journal of Infectious Diseases, doi:10.1016/j.bjid.2021.101549 Hydroxychloroquine with azithromycin in patients hospitalized for mild and moderate COVID-19
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 m..
Feb 18
2021
Awad et al., American Journal of Health-System Pharmacy, doi:10.1093/ajhp/zxab056 Impact of hydroxychloroquine on disease progression and ICU admissions in patients with SARS-CoV-2 infection
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, IC..
Feb 15
2021
Mahto et al., American Journal of Blood Research, 11:1 Seroprevalence of IgG against SARS-CoV-2 and its determinants among healthcare workers of a COVID-19 dedicated hospital of India
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 11
2021
Lora-Tamayo et al., J. Infection, doi:10.1016/j.jinf.2021.02.011 Early Lopinavir/ritonavir does not reduce mortality in COVID-19 patients: results of a large multicenter study
50% lower mortality [p<0.0001]. Lopinavir/ritonavir retrospective study also showing univariate results for HCQ, with significantly lower mortality.
Feb 10
2021
Desai et al., J. Clinical Medicine, doi:10.3390/jcm10040686 The Use of Antiviral Agents against SARS-CoV-2: Ineffective or Time and Age Dependent Result? A Retrospective, Observational Study among COVID-19 Older Adults
Retrospective 143 COVID-19 hospitalized patients >65yo, showing adjusted OR for antiviral treatment starting within 6 days of 0.44 [0.2-0.9], p = 0.02, compared to treatment started later.
Feb 9
2021
Lounnas e al., Archives of Microbiology & Immunology, doi: (meta analysis) Revisiting a Meta-analysis Shows that Hydroxychloroquine with Azithromycin may be Efficient in Covid-19 patients
Analysis of the Fiolet meta analysis and correction of bias evaluation, showing HCQ RR 0.45 [0.31-0.59], and HCQ+AZ RR 0.34 [0.06-0.61].
Feb 9
2021
Purwati et al., Biochemistry Research International, doi:10.1155/2021/6685921 A Randomized, Double-Blind, Multicenter Clinical Study Comparing the Efficacy and Safety of a Drug Combination of Lopinavir/Ritonavir-Azithromycin, Lopinavir/Ritonavir-Doxycycline, and Azithromycin-Hydroxychloroquine for Patients Diagnosed with Mild to Moderate COVID-19 Infections
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 ap..
Feb 5
2021
Fitzgerald et al., medRxiv, doi:10.1101/2021.02.03.21251069 (Preprint) Risk Factors for Infection and Health Impacts of the COVID-19 Pandemic in People with Autoimmune Diseases
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 ..
Feb 5
2021
Hernandez-Cardenas et al., medRxiv, doi:10.1101/2021.02.01.21250371 (Preprint) Hydroxychloroquine for the treatment of severe respiratory infection by COVID-19: a randomized controlled trial
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..
Feb 5
2021
Ouedraogo et al., Revue des Maladies Respiratoires, doi:10.1016/j.rmr.2021.02.001 Factors associated with the occurrence of acute respiratory distress and death in patients with COVID-19 in Burkina Faso
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 1
2021
Alexander et al., medRxiv, doi:10.1101/2021.01.28.21250706 (Review) (Preprint) Early Multidrug Outpatient Treatment of SARS-CoV-2 Infection (COVID-19) and Reduced Mortality Among Nursing Home Residents
Review of studies on treatment of COVID-19 for nursing home residents, concluding that there is a large >60% mortality risk reduction associated with multidrug treatment using two or more intracellular anti-infectives (HCQ and either AZM ..
Feb 1
2021
Ubaldo et al., Critical Care Research and Practice, 10.1155/2021/7510306 COVID-19: A Single-Center ICU Experience of the First Wave in the Philippines
18% lower mortality [p=0.64]. Retrospective ICU patients in the Philippines showing unadjusted HCQ RR 0.82, p = 0.64.
Jan 31
2021
Naderi et al., Immunopathologia Persa, doi:10.34172/ipp.2021.29 (Preprint) Prophylactic effects of hydroxychloroquine on the incidence of COVID-19 in patients with rheumatic arthritis: an observational cohort study
Prospective observational study of 215 RA patients treated with HCQ showing 9 cases, 1 hospitalization (without ICU/intubation), and no mortality.
Jan 31
2021
Roig et al., Revista Espanola de Quimioterapia, doi:10.37201/req/130.2020 Clinical and pharmacological data in COVID-19 hospitalized nonagenarian patients
16% lower mortality [p=0.76]. Retrospective 79 hospitalized nonagenarian patients showing unadjusted HCQ mortality RR 0.84, p = 0.76.
Jan 29
2021
Di Castelnuovo et al., Journal of Healthcare Engineering, doi:10.1155/2021/5556207 (date from earlier preprint) Disentangling the Association of Hydroxychloroquine Treatment with Mortality in Covid-19 Hospitalized Patients through Hierarchical Clustering
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 27
2021
Trefond et al., Revue du Rhumatisme, doi:10.1016/j.rhum.2021.09.004 (date from earlier preprint) Effet d’un traitement par hydroxychloroquine prescrit comme traitement de fond de rhumatismes inflammatoires chroniques ou maladies auto-immunes systémiques sur les tests diagnostiques et l’évolution de l’infection à SARS CoV-2: étude de 871 patients
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 extre..
Jan 26
2021
Eftekhar et al., medRxiv, doi:10.1101/2021.01.16.21249941 (Preprint) Hydroxychloroquine and azithromycin: As a double edge sword for COVID-19?
Retrospective 172 hospitalized patients, 83% treated and HCQ+AZ and 17% with HCQ, not finding a significant difference in QTc prolongation, but recommending careful monitoring for the use of HCQ+AZ; especially in males, patients with high..
Jan 25
2021
Dabbous et al., Archives of Virology, doi:10.1007/s00705-021-04956-9 Efficacy of favipiravir in COVID-19 treatment: a multi-center randomized study
This study was retracted.
Jan 25
2021
Hussein et al., Journal of Molecular Structure, doi:10.1016/j.molstruc.2021.129979 Molecular Docking Identification for the efficacy of Some Zinc Complexes with Chloroquine and Hydroxychloroquine against Main Protease of COVID-19
Molecular dynamics analysis recommending Zn (CQ) Cl2(H2O) and Zn (HCQ) Cl2(H2O) as potential inhibitors for COVID-19 Mpro. Zn (HCQ) Cl2(H2O) exhibited a strong binding to the main protease receptor, forming eight hydrogen bonds.
Jan 24
2021
Zelenko, Z., Preprint (Preprint) Nebulized Hydroxychloroquine for COVID-19 Treatment: 80x Improvement in Breathing
Report on the use of nebulized HCQ showing much more rapid improvement compared to tablets, with 95% of patients experiencing improved breathing within 1 hour. Author notes that the effectiveness of HCQ is time and dose dependent, with a ..
Jan 23
2021
Cifuentes et al., Medicina Clínica (English Edition), doi:10.1016/j.medcle.2020.10.012 Incidence of COVID-19 in patients under chronic treatment with hydroxychloroquine
Retrospective 3,817 chronic HCQ patients showing 4.4% COVID-19 positive rate, 1.3% severe. There is no comparison with a control group. Authors note that there was a 3.6% incidence among 2,032,863 patients in one of the regions (Castilla ..
Jan 18
2021
Li et al., Science China Life Sciences, doi:10.1007/s11427-020-1871-4 Evaluation of the efficacy and safety of hydroxychloroquine in comparison with chloroquine in moderate and severe patients with COVID-19
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..
Jan 13
2021
Khoubnasabjafari et al., Postgraduate Medical Journal, doi:10.1136/postgradmedj-2020-139561 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
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 12
2021
Li et al., Research Square, doi:10.21203/rs.3.rs-119202/v1 (Preprint) Treatment of COVID-19 patients with hydroxychloroquine or chloroquine: A retrospective analysis
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 ho..
Jan 10
2021
Rangel et al., Journal of the American Academy of Dermatology, doi:10.1016/j.jaad.2020.10.098 Chronic Hydroxychloroquine Therapy and COVID-19 Outcomes: A Retrospective Case-Control Analysis
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 sign..
Jan 8
2021
Yegerov et al., medRxiv, doi:10.1101/2021.01.06.20249091 (Preprint) Epidemiological and Clinical Characteristics, and Virologic Features of COVID-19 Patients in Kazakhstan: a Nation-Wide, Retrospective, Cohort 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 7
2021
Baildya et al., Journal of Molecular Structure, doi:10.1016/j.molstruc.2021.129891 Inhibitory capacity of Chloroquine against SARS-COV-2 by effective binding with Angiotensin converting enzyme-2 receptor: An insight from molecular docking and MD-simulation studies
Molecular docking study of 16 drugs showing CQ had the highest binding affinity with ACE2, and molecular dynamics study of the docked CQ-ACE2 structure. Authors conclude that CQ binds reasonably strongly with ACE2 and the stable ACE2-CQ m..
Jan 6
2021
Noureddine et al., Journal of King Saud University - Science, doi:10.1016/j.jksus.2020.101334 Quantum chemical studies on molecular structure, AIM, ELF, RDG and antiviral activities of hybrid hydroxychloroquine in the treatment of COVID-19: molecular docking and DFT calculations
In silico analysis of hydroxychloroquine and hydroxychloroquine sulfate predicting that hydroxychloroquine sulfate is more stable and effective for COVID-19.
Jan 4
2021
Gautret et al., International Journal of Antimicrobial Agents, doi:10.1016/j.ijantimicag.2020.106236 Safety profile of hydroxychloroquine and azithromycin combined treatment in COVID-19 patients
Report on the safety of HCQ+AZ with 3,737 COVID-19 patients. 138 had contraindications and treatment was discontinued in 12 cases due to QTc prolongation. There were no cases of torsade de pointe or sudden death.
Jan 2
2021
Sarfaraz et al., medRxiv, doi:10.1101/2020.12.28.20248920 (Preprint) Determinants of in-hospital mortality in COVID-19; a prospective cohort study from Pakistan
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 1
2021
Lotfy et al., Turk. Thorac. J., doi:10.5152/TurkThoracJ.2021.20180 Use of Hydroxychloroquine in Patients with COVID-19: A Retrospective Observational 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 confou..
Jan 1
2021
Sands et al., International Journal of Infectious Diseases, doi:/10.1016/j.ijid.2020.12.060 No clinical benefit in mortality associated with hydroxychloroquine treatment in patients with COVID-19
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 th..
Dec 31
2020
Mahale et al., Indian Journal of Critical Care Medicine, doi:10.5005/jp-journals-10071-23599 A Retrospective Observational Study of Hypoxic COVID-19 Patients Treated with Immunomodulatory Drugs in a Tertiary Care Hospital
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 31
2020
Matada et al., Bioorganic & Medicinal Chemistry, doi:10.1016/j.bmc.2020.115973 (Review) A comprehensive review on the biological interest of quinoline and its derivatives
Review of quinolone and derivatives, natural and drug sources, and biological activity.
Dec 31
2020
Psevdos et al., Open Forum Infectious Diseases, doi:10.1093/ofid/ofaa439.721 Corona Virus Disease-19 (COVID-19) in a Veterans Affairs Hospital at Suffolk County, Long Island, New York
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 sus..
Dec 31
2020
Texeira et al., Open Forum Infectious Diseases, doi:10.1093/ofid/ofaa439.560 Characteristics and outcomes of COVID-19 patients admitted to a regional health system in the southeast
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 su..
Dec 31
2020
Vernaz et al., Swiss Medical Weekly, doi:10.4414/smw.2020.20446 Early experimental COVID-19 therapies: associations with length of hospital stay, mortality and related costs
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 wi..
Dec 30
2020
McCullough et al., Reviews in Cardiovascular Medicine, doi:10.31083/j.rcm.2020.04.264 (Review) Multifaceted highly targeted sequential multidrug treatment of early ambulatory high-risk SARS-CoV-2 infection (COVID-19)
Review urging early treatment of COVID-19 with sequential multidrug treatment that has been shown to be safe and effective. Proposed treatment includes zinc, vitamin D & C, quercetin, and depending on age, comorbidities, and symptoms may ..
Dec 30
2020
Procter et al., Reviews in Cardiovascular Medicine, doi:10.31083/j.rcm.2020.04.260 Clinical outcomes after early ambulatory multidrug therapy for high-risk SARS-CoV-2 (COVID-19) infection
Retrospective 922 outpatients, with 320 treated early due to age>50 or comorbidities, showing 2.2% hospitalization and 0.3% death, which authors note is considerably lower than reported in other studies in their region. At least two of zi..
Dec 29
2020
Güner et al., Journal of Infection and Public Health, doi:10.1016/j.jiph.2020.12.017 Comparing ICU Admission Rates of Mild/Moderate COVID-19 Patients Treated with Hydroxychloroquine, Favipiravir, and Hydroxychloroquine plus Favipiravir
77% lower ICU admission [p=0.16]. Retrospective 824 hospitalized patients in Turkey showing lower ICU admission for HCQ vs. favipiravir.
Dec 28
2020
Cordtz et al., Rheumatology, doi:10.1093/rheumatology/keaa897 Incidence and severeness of COVID-19 hospitalisation in patients with inflammatory rheumatic disease: a nationwide cohort study from Denmark
Retrospective 58,052 rheumatic disease patients in Denmark showing that RA patients have a higher risk of COVID-19 hospitalization in general. HCQ treated patients show lower risk, although this is not statistically significant with only ..
Dec 24
2020
Chari et al., Blood, doi:10.1182/blood.2020008150 Clinical features associated with COVID-19 outcome in multiple myeloma: first results from the International Myeloma Society data set
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 23
2020
Su et al., BioScience Trends, doi:10.5582/bst.2020.03340 Efficacy of early hydroxychloroquine treatment in preventing COVID-19 pneumonia aggravation, the experience from Shanghai, China
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 23
2020
Taccone et al., The Lancet Regional Health - Europe, doi:10.1016/j.lanepe.2020.100019 The role of organizational characteristics on the outcome of COVID-19 patients admitted to the ICU in Belgium
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 22
2020
Cangiano et al., Aging, doi:10.18632/aging.202307 Mortality in an Italian nursing home during COVID-19 pandemic: correlation with gender, age, ADL, vitamin D supplementation, and limitations of the diagnostic tests
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..
Dec 19
2020
Huh et al., International Journal of Infectious Diseases, doi:10.1016/j.ijid.2020.12.041 Association of prescribed medications with the risk of COVID-19 infection and severity among adults in South Korea
251% 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 ..
Dec 18
2020
Matangila et al., PLoS ONE, doi:10.1371/journal.pone.0244272 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
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 16
2020
Signes-Costa et al., Archivos de Bronconeumología, doi:10.1016/j.arbres.2020.11.012 Prevalence and 30-day mortality in hospitalized patients with COVID-19 and prior lung diseases
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...
Dec 16
2020
Gönenli et al., Research Square, doi:0.21203/rs.3.rs-107937/v1 (Preprint) Prophylactic use of Hydroxychloroquine among Physicians working in Pandemic Hospitals
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 ..
Dec 14
2020
De Luna et al., medRxiv, doi:10.1101/2020.12.11.20247437 (Preprint) Clinical and Demographic Characteristics of COVID-19 Patients Admitted in a Tertiary Care Hospital in the Dominican Republic
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 14
2020
Sofian et al., Wiener Medizinische Wochenschrift, doi:10.1007/s10354-020-00793-8 SARS-CoV‑2, a virus with many faces: a series of cases with prolonged persistence of COVID-19 symptoms
Report on a series of 10 patients experiencing prolonged COVID-19 symptoms that were given HCQ 250mg bid for 5 days, with resolution of symptoms in all cases, and patients reporting they felt much better 2 days after treatment initiation.
Dec 14
2020
Orioli et al., Diabetes & Metabolic Syndrome: Clinical Research & Reviews, doi:10.1016/j.dsx.2020.12.020 Clinical characteristics and short-term prognosis of in-patients with diabetes and COVID-19: A retrospective study from an academic center in Belgium
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 14
2020
Naseem et al., medRxiv, doi:10.1101/2020.12.13.20247254 (Preprint) Predicting mortality in SARS-COV-2 (COVID-19) positive patients in the inpatient setting using a Novel Deep Neural Network
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 14
2020
Tan et al., Virus Research, doi:10.1016/j.virusres.2020.198262 A retrospective comparison of drugs against COVID-19
35% shorter hospitalization [p=0.04]. Retrospective 333 patients in China, with only 8 HCQ patients, showing shorter duration of hospitalization with HCQ.
Dec 11
2020
Bielza et al., Journal of the American Medical Directors Association, doi:10.1016/j.jamda.2020.12.003 Clinical characteristics, frailty and mortality of residents with COVID-19 in nursing homes of a region of Madrid
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). Med..
Dec 11
2020
Sogut et al., The American Journal of Emergency Medicine, doi:10.1016/j.ajem.2020.12.014 Safety and efficacy of hydroxychloroquine in 152 outpatients with confirmed COVID-19: A pilot observational study
Safety study of 152 outpatients concluding that HCQ is safe for COVID-19, was well tolerated, and was not associated with a risk of ventricular arrhythmia due to drug-induced QTc interval prolongation.
Dec 11
2020
Jung et al., Clinical Microbiology and Infection, doi:10.1016/j.cmi.2020.12.003 Effect of hydroxychloroquine pre-exposure on infection with SARS-CoV-2 in rheumatic disease patients: A population-based cohort 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 ..
Dec 10
2020
Rosenthal et al., JAMA Network Open, doi:10.1001/jamanetworkopen.2020.29058 Risk Factors Associated With In-Hospital Mortality in a US National Sample of Patients With COVID-19
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 significan..
Dec 10
2020
Alqassieh et al., F1000Research, Preprint (Preprint) Clinical characteristics and predictors of the duration of hospital stay in COVID-19 patients in Jordan
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 10
2020
Italian Council of State (News) Consiglio di Stato, sì all'uso dell'idrossiclorachina per la cura del Covid
Consiglio di Stato ruling in Italy re-establishes the right of Italian MDs to prescribe HCQ, which was suspended after the retracted Lancet study.
Dec 9
2020
Johnston et al., EClinicalMedicine, doi:10.1016/j.eclinm.2021.100773 (date from earlier preprint) Hydroxychloroquine with or Without Azithromycin for Treatment of Early SARS-CoV-2 Infection Among High-Risk Outpatient Adults: A Randomized Clinical Trial
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..
Dec 9
2020
Agusti et al., Enfermedades Infecciosas y Microbiología Clínica, doi:10.1016/j.eimc.2020.10.023 Efficacy and safety of hydroxychloroquine in healthcare professionals with mild SARS-CoV-2 infection: prospective, non-randomized trial
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. Prospecti..
Dec 9
2020
Guglielmetti et al., Journal of Infection and Public Health, doi:10.1016/j.jiph.2020.11.012 Severe COVID-19 pneumonia in Piacenza, Italy – a cohort study of the first pandemic wave
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 7
2020
Barnabas et al., Annals of Internal Medicine, doi:10.7326/M20-6519 Hydroxychloroquine for Post-exposure Prophylaxis to Prevent Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2) Infection: A Randomized Trial
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..
Dec 4
2020
Ozturk et al., Nephrology Dialysis Transplantation, doi:10.1093/ndt/gfaa271 Mortality analysis of COVID-19 infection in chronic kidney disease, haemodialysis and renal transplant patients compared with patients without kidney disease: a nationwide analysis from Turkey
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 4
2020
Modrák et al., medRxiv, doi:10.1101/2020.12.03.20239863 (Preprint) Detailed disease progression of 213 patients hospitalized with Covid-19 in the Czech Republic: An exploratory analysis
59% lower mortality [p=0.04]. Retrospective 213 hospitalized patients in Czech Republic showing lower mortality with HCQ. Subject to confounding by indication.
Dec 4
2020
Peng et al., Nephrology Dialysis Transplantation, doi:10.1093/ndt/gfaa288 Early versus late acute kidney injury among patients with COVID-19—a multicenter study from Wuhan, China
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 2
2020
Wiseman et al., medRxiv, doi:10.1101/2020.11.29.20235218 (Preprint) (meta analysis) Effective post-exposure prophylaxis of Covid-19 is associated with use of hydroxychloroquine: Prospective re-analysis of a public dataset incorporating novel data
42% fewer cases [p=0.04]. 6th independent analysis showing efficacy from the Boulware PEP trial. This prospective analysis corrects an error in the NEJM paper where shipping delays are omitted (still not corrected). 42% reduction in COVID-19 (9.6% vs. 16.5%), RR 0..
Dec 1
2020
Capsoni et al., Research Square, doi:10.21203/rs.3.rs-113418/v1 (Preprint) CPAP Treatment In COVID-19 Patients: A Retrospective Observational Study In The Emergency Department
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 30
2020
Abdulrahman et al., medRxiv, doi:10.1101/2020.11.25.20234914 (Preprint) The efficacy and safety of hydroxychloroquine in COVID19 patients : a multicenter national retrospective cohort
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..
Nov 29
2020
Abd-Elsalam et al., Biological Trace Element Research, doi:10.1007/s12011-020-02512-1 Do Zinc Supplements Enhance the Clinical Efficacy of Hydroxychloroquine?: a Randomized, Multicenter Trial
191 patient RCT in Egypt comparing the addition of zinc to HCQ, not showing a significant difference. No information on baseline zinc values was recorded. We note that Egypt has a low rate of zinc deficiency so supplementation is less lik..
Nov 28
2020
Lambermont et al., Critical Care Explorations, doi:10.1097/CCE.0000000000000305 Predictors of Mortality and Effect of Drug Therapies in Mechanically Ventilated Patients With Coronavirus Disease 2019: A Multicenter Cohort 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 spe..
Nov 28
2020
Ruiz et al., International Journal of Antimicrobial Agents, doi:10.1016/j.ijantimicag.2020.106247 Hydroxychloroquine lung pharmacokinetics in critically ill patients infected with COVID-19
HCQ lung pharmacokinetic study confirming that lung concentrations can be much higher than plasma and exceed predicted EC50 values. The median lung epithelial lining fluid concentration was 38 times higher than plasma concentrations. 22 C..
Nov 28
2020
Rodriguez-Gonzalez et al., International Journal of Antimicrobial Agents, doi:10.1016/j.ijantimicag.2020.106249 COVID-19 in hospitalized patients in Spain: a cohort study in Madrid
23% lower mortality [p=0.26]. Retrospective 1255 patients in Spain showing lower mortality with HCQ. Subject to confounding by indication.
Nov 27
2020
van Halem et al., BMC Infect Dis., doi:10.1186/s12879-020-05605-3 Risk factors for mortality in hospitalized patients with COVID-19 at the start of the pandemic in Belgium: a retrospective cohort study
32% lower mortality [p=0.05]. Retrospective 319 hospitalized patients in Belgium showing lower mortality with HCQ, although not reported to be statistically significant.
Nov 26
2020
Burdick et al., Journal of Clinical Medicine, doi:10.3390/jcm9123834 Is Machine Learning a Better Way to IdentifyCOVID-19 Patients Who Might Benefit fromHydroxychloroquineTreatment?—The IDENTIFY Trial
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 lea..
Nov 24
2020
Abbas et al., Int. J. Clin. Pract., doi:10.1111/ijcp.13856 Assessment of COVID-19 Treatment containing both Hydroxychloroquine and Azithromycin: A Natural Clinical Trial
Prospective study of 161 hospitalized patients in Iraq showing HCQ+AZ appears to help recovery. Most mortality was in patients that were already in critical condition on admission and died before treatment could be effective.
Nov 23
2020
Qin et al., Thrombosis Research, doi:10.1016/j.thromres.2020.11.020 Low molecular weight heparin and 28-day mortality among patients with coronavirus disease 2019: A cohort study in the early epidemic era
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 21
2020
Revollo et al., Journal of Antimicrobial Chemotherapy, doi:10.1093/jac/dkaa477 Hydroxychloroquine pre-exposure prophylaxis for COVID-19 in healthcare workers
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 n..
Nov 20
2020
Omrani et al., EClinicalMedicine, doi:10.1016/j.eclinm.2020.100645 Randomized double-blinded placebo-controlled trial of hydroxychloroquine with or without azithromycin for virologic cure of non-severe Covid-19
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-infect..
Nov 19
2020
Falcone et al., Open Forum Infectious Diseases, doi:10.1093/ofid/ofaa563 Role of low-molecular weight heparin in hospitalized patients with SARS-CoV-2 pneumonia: a prospective observational 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, pro..
Nov 18
2020
Budhiraja et al., medRxiv, doi:10.1101/2020.11.16.20232223 (Preprint) Clinical Profile of First 1000 COVID-19 Cases Admitted at Tertiary Care Hospitals and the Correlates of their Mortality: An Indian Experience
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 H..
Nov 17
2020
Boari et al, Biosci. Rep., doi:10.1042/BSR20203455 Prognostic factors and predictors of outcome in patients with COVID-19 and related pneumonia: a retrospective cohort 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 13
2020
Sheshah et al., Diabetes Research and Clinical Practice, doi:10.1016/j.diabres.2020.108538 Prevalence of Diabetes, Management and Outcomes among Covid-19 Adult Patients Admitted in a Specialized Tertiary Hospital in Riyadh, Saudi Arabia
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 12
2020
Simova et al., New Microbes and New Infections, doi:10.1016/j.nmni.2020.100813 Hydroxychloroquine for prophylaxis and treatment of COVID-19 in health care workers
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 t..
Nov 12
2020
Simova et al., New Microbes and New Infections, doi:10.1016/j.nmni.2020.100813 Hydroxychloroquine for prophylaxis and treatment of COVID-19 in health care workers
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 pa..
Nov 12
2020
Tchounga et al., Journal of Pharmaceutical and Biomedical Analysis, doi:10.1016/j.jpba.2020.113761 (meta analysis) Composition analysis of falsified chloroquine phosphate samples seized during the COVID-19 pandemic
Analysis of fake CQ tablets finding: - no CQ in six samples, substituted with metronidazole (at sub-therapeutic levels) or paracetamol. - trace levels of paracetamol and chloramphenicol in four and two samples respectively. - CQ levels to..
Nov 11
2020
Águila-Gordo et al., Revista Española de Geriatría y Gerontología, doi:10.1016/j.regg.2020.09.006 Mortality and associated prognostic factors in elderly and very elderly hospitalized patients with respiratory disease COVID-19
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 9
2020
Khamis et al., International Journal of Infectious Diseases, doi:10.1016/j.ijid.2020.11.008 Randomized Controlled Open Label Trial on the Use of Favipiravir Combined with Inhaled Interferon beta-1b in Hospitalized Patients with Moderate to Severe COVID-19 Pneumonia
Small 89 patient RCT comparing favipiravir and inhaled interferon with HCQ for moderate to severe COVID-19 pneumonia, not finding significant differences.
Nov 9
2020
Rodriguez et al., Medicina Intensiva, doi:10.1016/j.medine.2020.05.005 Severe infection due to the SARS-CoV-2 coronavirus: Experience of a tertiary hospital with COVID-19 patients during the 2020 pandemic
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 9
2020
Self et al., JAMA, doi:10.1001/jama.2020.22240 Effect of Hydroxychloroquine on Clinical Status at 14 Days in Hospitalized Patients With COVID-19: A Randomized Clinical Trial
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), t..
Nov 9
2020
Brown et al., Annals of the American Thoracic Society, doi:10.1513/AnnalsATS.202008-940OC Hydroxychloroquine vs. Azithromycin for Hospitalized Patients with COVID-19 (HAHPS): Results of a Randomized, Active Comparator Trial
Small early terminated very late stage (86% on oxygen, 44% enrolled in the ICU) RCT comparing HCQ vs. AZ, not finding a significant difference between the two treatments. There is no comparison with a control group. HCQ patients not in th..
Nov 9
2020
Núñez-Gil et al., Intern. Emerg. Med., doi:10.1007/s11739-020-02543-5 Mortality risk assessment in Spain and Italy, insights of the HOPE COVID-19 registry
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 6
2020
Mathai et al., J. Marine Medical Society, doi:10.4103/jmms.jmms_115_20 Hydroxychloroquine as pre-exposure prophylaxis against COVID-19 in health-care workers: A single-center experience
90% fewer cases [p<0.0001]. 90% reduction in cases with HCQ pre-exposure prophylaxis. Retrospective 604 healthcare workers.
Nov 6
2020
Datta et al., Journal of Vaccines & Vaccination, S6:1000002 No Role of HCQ in COVID-19 Prophylaxis: A Survey amongst Indian Doctors
22% fewer cases [p=0.47]. Survey of Indian doctors not finding a significant effect of HCQ prophylaxis.
Nov 6
2020
Dhibar et al., International Journal of Antimicrobial Agents, doi:10.1016/j.ijantimicag.2020.106224 Post Exposure Prophylaxis with Hydroxychloroquine (HCQ) for the Prevention of COVID-19, a Myth or a Reality? The PEP-CQ Study
41% fewer cases [p=0.03] and 44% fewer symptomatic cases [p=0.21]. 41% reduction in cases with HCQ PEP. Prospective open label trial with 132 HCQ patients and 185 control patients showing RR 0.59, p=0.03. 50% reduction in PCR+ cases, 44% reduction in symptomatic cases. No serious adverse events. Relative..
Nov 5
2020
Maldonado et al., Nefrología, doi:10.1016/j.nefro.2020.09.002 COVID-19 incidence and outcomes in a home dialysis unit in Madrid (Spain) at the height of the pandemic
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 5
2020
Rodriguez-Nava et al., Mayo Clinic Proceedings: Innovations, Quality & Outcomes Clinical characteristics and risk factors for mortality of hospitalized patients with COVID-19 in a community hospital: A retrospective cohort 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 4
2020
Salazar et al., The American Journal of Pathology, doi:10.1016/j.ajpath.2020.10.008 Significantly Decreased Mortality in a Large Cohort of Coronavirus Disease 2019 (COVID-19) Patients Transfused Early with Convalescent Plasma Containing High-Titer Anti–Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2) Spike Protein IgG
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 4
2020
Cadegiani et al., New Microbes and New Infections, doi:10.1016/j.nmni.2021.100915 (date from earlier preprint) Early COVID-19 Therapy with azithromycin plus nitazoxanide, ivermectin or hydroxychloroquine in Outpatient Settings Significantly Improved COVID-19 outcomes compared to Known outcomes in untreated patients
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, ev..
Nov 3
2020
Behera et al., PLoS ONE, doi:10.1371/journal.pone.0247163 (date from earlier preprint) Role of ivermectin in the prevention of SARS-CoV-2 infection among healthcare workers in India: A matched case-control 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..
Nov 2
2020
López et al., Annals of Pediatrics, doi:10.1016/j.anpedi.2020.10.017 Telemedicine follow-ups for COVID-19: experience in a tertiary hospital
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 1
2020
Niwas et al., Advances in Respiratory Medicine, doi:10.5603/ARM.a2020.0139 Clinical outcome, viral response and safety profile of chloroquine in COVID-19 patients — initial experience
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 31
2020
Szente Fonseca et al., Travel Medicine and Infectious Disease, doi:10.1016/j.tmaid.2020.101906 Risk of Hospitalization for Covid-19 Outpatients Treated with Various Drug Regimens in Brazil: Comparative Analysis
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 30
2020
Tehrani et al., International Journal of Infectious Diseases, doi:10.1016/j.ijid.2020.10.071 Risk factors for mortality in adult COVID-19 patients: frailty predicts fatal outcome in older patients
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 27
2020
Arleo et al., medRxiv, doi:10.1101/2020.10.26.20219154 (Preprint) Clinical Course and Outcomes of coronavirus disease 2019 (COVID-19) in Rheumatic Disease Patients on Immunosuppression: A case Cohort Study at a Single Center with a Significantly Diverse Population
50% lower mortality [p=0.67]. Retrospective hospitalized rheumatic disease patients showing 50% lower mortality for patients on HCQ.
Oct 27
2020
Choi et al., International Journal of Infectious Diseases, doi:10.1016/j.ijid.2020.10.062 Comparison of antiviral effect for mild-to-moderate COVID-19 cases between lopinavir/ritonavir versus hydroxychloroquine: A nationwide propensity score-matched cohort 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 ..
Oct 26
2020
Frontera et al., Research Square, doi:10.21203/rs.3.rs-94509/v1 (Preprint) Treatment with Zinc is Associated with Reduced In-Hospital Mortality Among COVID-19 Patients: A Multi-Center Cohort Study
37% lower mortality [p=0.02]. Retrospective 3,473 hospitalized patients showing lower mortality with HCQ+zinc.
Oct 24
2020
Goenka et al., SSRN, doi:10.2139/ssrn.3689618 (Preprint) Seroprevalence of COVID-19 Amongst Health Care Workers in a Tertiary Care Hospital of a Metropolitan City from India
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 23
2020
Coll et al., American Journal of Transplantation, doi:10.1111/ajt.16369 Covid-19 in transplant recipients: the spanish experience
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 21
2020
Lano et al., Clinical Kidney Journal, 13:5, October 2020, 878–888, doi:10.1093/ckj/sfaa199 Risk factors for severity of COVID-19 in chronic dialysis patients from a multicentre French cohort
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 21
2020
Dubee et al., Clinical Microbiology and Infection, doi:10.1016/j.cmi.2021.03.005 (date from earlier preprint) Hydroxychloroquine in mild-to-moderate COVID-19: a placebo-controlled double blind trial
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 ..
Oct 21
2020
Ñamendys-Silva et al., Heart & Lung, doi:10.1016/j.hrtlng.2020.10.013 Outcomes of patients with COVID-19 in the Intensive Care Unit in Mexico: A multicenter observational 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...
Oct 20
2020
IHU Marseille (Preprint) (meta analysis) Meta-analysis on chloroquine derivatives and COVID-19 mortality
Updated meta analysis of 41 studies showing CQ/HCQ OR 0.57, p<0.0001 from clinical studies. For big data studies authors find inconsistent results and OR 0.83, p=0.0014, and for all studies combined OR 0.72, p<0.0001.
Oct 20
2020
Solh et al., medRxiv, doi:10.1101/2020.10.16.20214130 (Preprint) Clinical course and outcome of COVID-19 acute respiratory distress syndrome: data from a national repository
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 us..
Oct 17
2020
Mohana et al., International Journal of Infectious Diseases, doi:10.1016/j.ijid.2020.10.031 (date from earlier preprint) Hydroxychloroquine Safety Outcome within Approved Therapeutic Protocol for COVID-19 Outpatients in Saudi Arabia
Safety study of 2,733 patients in Saudi Arabia showing HCQ in mild to moderate cases in an outpatient setting, within the protocol recommendation and inclusion/exclusion criteria, is safe, highly tolerable, and has minimal side effects. N..
Oct 15
2020
Guisado-Vasco Clinical characteristics and outcomes among hospitalized adults with severe COVID-19 admitted to a tertiary medical center and receiving antiviral, antimalarials, glucocorticoids, or immunomodulation with tocilizumab or cyclosporine: A retrospective observational study (COQUIMA cohort)
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)...
Oct 15
2020
SOLIDARITY Trial Consortium, NEJM, doi:10.1056/NEJMoa2023184 (date from earlier preprint) Repurposed antiviral drugs for COVID-19; interim WHO SOLIDARITY trial results
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 da..
Oct 12
2020
Annie et al., Pharmacotherapy, doi:10.1002/phar.2467 Hydroxychloroquine in hospitalized COVID‐19 patients: Real world experience assessing mortality
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 11
2020
Sili et al., medRxiv, doi:10.1101/2020.10.09.20209775 (Preprint) Factors associated with progression to critical illness in 28 days among COVID-19 patients: results from a tertiary care hospital in Istanbul, Turkey
Analysis of hospitalized patients in Turkey showing HCQ was given to 99.2% of patients and the incidence of critical illness was lower than most studies. Authors note "whether HCQ administration lowered the rates of critical illness ..
Oct 8
2020
Aparisi et al., medRxiv, doi:10.1101/2020.10.06.20207092 (Preprint) Low-density lipoprotein cholesterol levels are associated with poor clinical outcomes in COVID-19
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 8
2020
Soto-Becerra et al., medRxiv, doi:10.1101/2020.10.06.20208066 (Preprint) 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
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 ..
Oct 6
2020
Ader et al., medRxiv, doi:10.1101/2022.02.16.22271064 (Preprint) An open-label randomized, controlled trial of the effect of lopinavir/ritonavir, lopinavir/ritonavir plus IFN-beta-1a and hydroxychloroquine in hospitalized patients with COVID-19 - Final results from the DisCoVeRy trial
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 5
2020
Mori et al., Journal of Microbiology, Immunology and Infection, doi:10.1016/j.jmii.2020.09.003 Triple therapy with hydroxychloroquine, azithromycin, and ciclesonide for COVID-19 pneumonia
Small case study of 5 patients in Japan showing improvement with HCQ+AZ+ciclesonide.
Oct 5
2020
Prodromos et al., New Microbes and New Infections, doi:10.1016/j.nmni.2020.100776 (meta analysis) Hydroxychloroquine is effective, and consistently so used early, for Covid-19: A systematic review
Meta analysis of 43 studies: "HCQ was found consistently effective against COVID-19 when used early, in the outpatient setting. It was found overall effective also including inpatient studies. No unbiased study found worse outcomes w..
Oct 2
2020
Nachega et al., The American Journal of Tropical Medicine and Hygiene, doi:10.4269/ajtmh.20-1240 Clinical Characteristics and Outcomes of Patients Hospitalized for COVID-19 in Africa: Early Insights from the Democratic Republic of the Congo
28% lower mortality [p=0.17] and 26% better 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 adju..
Oct 1
2020
Almazrou et al., Saudi Pharmaceutical Journal, doi:10.1016/j.jsps.2020.09.019 Comparing the impact of Hydroxychloroquine based regimens and standard treatment on COVID-19 patient outcomes: A retrospective cohort 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 30
2020
Yadav et al., ResearchGate, doi:10.13140/RG.2.2.34411.77603 (Preprint) Sero-survey for health-care workers provides corroborative evidence for the effectiveness of Hydroxychloroquine prophylaxis against COVID-19 infection
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 30
2020
Polat et al., Medical Journal of Bakirkoy, 16:3, 280-6, doi:10.5222/BMJ.2020.50469 Hydroxychloroquine Use on Healthcare Workers Exposed to COVID-19 - A Pandemic Hospital Experience
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...
Sep 30
2020
Ayerbe et al., Internal and Emergency Medicine, doi:0.1007/s11739-020-02505-x The association of treatment with hydroxychloroquine and hospital mortality in COVID-19 patients
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, tocilizu..
Sep 30
2020
Ladapo et al., medRxiv, doi:10.1101/2020.09.30.20204693 (Preprint) (meta analysis) Randomized Controlled Trials of Early Ambulatory Hydroxychloroquine in the Prevention of COVID-19 Infection, Hospitalization, and Death: Meta-Analysis
24% lower combined death/hospitalization/cases [p=0.03]. Meta analysis of prophylactic and early treatment RCTs, 24% reduction in cases, hospitalization or death with HCQ, RR 0.76, p=0.025. No serious adverse cardiac events were reported. 5,577 patients. The Boulware study provides a breakdown ..
Sep 30
2020
Abella et al., JAMA Internal Medicine, doi:doi:10.1001/jamainternmed.2020.6319 Efficacy and Safety of Hydroxychloroquine vs Placebo for Pre-exposure SARS-CoV-2 Prophylaxis Among Health Care Workers
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 ..
Sep 29
2020
Lammers et al., Int. J. Infectious Diseases, doi:10.1016/j.ijid.2020.09.1460 Early hydroxychloroquine but not chloroquine use reduces ICU admission in COVID-19 patients
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 ra..
Sep 29
2020
Dabbous et al., Scientific Reports, doi:10.1038/s41598-021-85227-0 (date from earlier preprint) Safety and efficacy of favipiravir versus hydroxychloroquine in management of COVID-19: A randomised controlled trial
This paper has been retracted [nature.com].
Sep 28
2020
Luco, J., Trends Med, doi:10.15761/TiM.1000268 (meta analysis) Hydroxychloroquine as post-exposure prophylaxis for Covid-19: Why simple data analysis can lead to the wrong conclusions from well-designed studies
Reanalysis of Boulware et al. PEP trial data showing statistically significant improvements with HCQ.
Sep 24
2020
Gasperetti et al., EP Europace, doi:10.1093/europace/euaa216 Arrhythmic safety of hydroxychloroquine in COVID-19 patients from different clinical settings
Safety study of 649 patients finding that HCQ administration is safe for short-term treatment for patients with COVID-19 infection regardless of the clinical setting of delivery, causing only modest QTc prolongation and no directly attrib..
Sep 24
2020
Shoaibi et al., medRxiv, doi:10.1101/2020.09.23.20199463 (Preprint) Comparative Effectiveness of Famotidine in Hospitalized COVID-19 Patients
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 23
2020
Ulrich et al., Open Forum Infectious Diseases, doi:10.1093/ofid/ofaa446 Treating Covid-19 With Hydroxychloroquine (TEACH): A Multicenter, Double-Blind, Randomized Controlled Trial in Hospitalized Patients
6% higher mortality [p=1]. 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, ..
Sep 22
2020
Serrano et al., Ann. Oncol., 2020, Sep, 31, S1026, doi:10.1016/j.annonc.2020.08.1830 COVID-19 and lung cancer: What do we know?
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 21
2020
Gentry et al., Lancet Rheumatology, doi:10.1016/S2665-9913(20)30305-2 Long-term hydroxychloroquine use in patients with rheumatic conditions and development of SARS-CoV-2 infection: a retrospective cohort 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 slight..
Sep 21
2020
Rajasingham et al., medRxiv, doi:10.1101/2020.09.18.20197327 Hydroxychloroquine as pre-exposure prophylaxis for COVID-19 in healthcare workers: a randomized trial
27% fewer cases [p=0.12]. PrEP RCT showing HR 0.73, p = 0.12. Trial halted after 47% enrollment, p < 0.05 will be reached at ~75% enrollment if similar results continue. HR 0.66/0.68 for full medication adherence, 0.72/0.74, p = 0.18/0.22 overall (1x/2x dosing). E..
Sep 21
2020
Grau-Pujol et al., Trials, doi:10.1186/s13063-021-05758-9 Pre-exposure prophylaxis with hydroxychloroquine for COVID-19: a double-blind, placebo-controlled randomized clinical trial
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 ..
Sep 21
2020
Lofgren et al., Open Forum Infectious Diseases, doi:10.1093/ofid/ofaa500 (date from earlier preprint) Safety of Hydroxychloroquine among Outpatient Clinical Trial Participants for COVID-19
Analysis of 2,795 outpatients not showing significant safety concerns with HCQ. No deaths were related to HCQ. There was one serious event requiring hospitalization, identical to the frequency with placebo.
Sep 18
2020
Axfors et al., Nature, doi:10.1038/s41467-021-22446-z (meta analysis) Mortality outcomes with hydroxychloroquine and chloroquine in COVID-19 from an international collaborative meta-analysis of randomized trials
Meta analysis assigning 89% weight to the RECOVERY and SOLIDARITY trials, producing the same result. These trials used excessively high non-patient-customized dosage in very sick late stage patients, results are not generalizable to typic..
Sep 16
2020
Karatza et al., Xenobiotica Optimization of hydroxychloroquine dosing scheme based on COVID-19 patients’ characteristics: a review of the literature and simulations
Analysis of HCQ dosing, suggesting that high initial doses followed by low and sparse doses may offer significant benefits to patients by decreasing the viral load without reaching levels considered to produce adverse effects. For instanc..
Sep 15
2020
Ashinyo et al., Pan African Medical Journal, 37:1, doi:10.11604/pamj.supp.2020.37.1.25718 Clinical characteristics, treatment regimen and duration of hospitalization among COVID-19 patients in Ghana: a retrospective cohort 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 14
2020
Lauriola et al., Clinical and Translational Science, doi:10.1111/cts.12860 Effect of combination therapy of hydroxychloroquine and azithromycin on mortality in COVID‐19 patients
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 13
2020
Sulaiman et al., medRxiv, doi:10.1101/2020.09.09.20184143 (Preprint) The Effect of Early Hydroxychloroquine-based Therapy in COVID-19 Patients in Ambulatory Care Settings: A Nationwide Prospective Cohort Study
64% lower mortality [p=0.01] and 39% lower hospitalization [p=0.001]. 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 ..
Sep 12
2020
Heberto et al., IJC Heart & Vasculature, doi:10.1016/j.ijcha.2020.100638 Implications of myocardial injury in Mexican hospitalized patients with coronavirus disease 2019 (COVID-19)
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 9
2020
Alamdari et al., Tohoku J. Exp. Med., 2020, 252, 73-84, doi:10.1620/tjem.252.73 Mortality Risk Factors among Hospitalized COVID-19 Patients in a Major Referral Center in Iran
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 t..
Sep 9
2020
Kirenga et al., BMJ Open Respiratory Research, doi:10.1136/bmjresp-2020-000646 Characteristics and outcomes of admitted patients infected with SARS-CoV-2 in Uganda
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 p..
Sep 9
2020
Rentsch et al., The Lancet Rheumatology, doi:10.1016/S2665-9913(20)30378-7 (preprint 9/9, https://www.medrxiv.org/content/10.1101/2020.09.04.20187781v1) Effect of pre-exposure use of hydroxychloroquine on COVID-19 mortality: a population-based cohort study in patients with rheumatoid arthritis or systemic lupus erythematosus using the OpenSAFELY platform
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 d..
Sep 9
2020
Laplana et al., PLOS ONE, doi:10.1371/journal.pone.0243598 Lack of protective effect of chloroquine derivatives on COVID-19 disease in a Spanish sample of chronically treated patients
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...
Sep 7
2020
IHU, Expert Review of Clinical Immunology (Review) Natural history and therapeutic options for COVID-19
Review of the current state of knowledge regarding the natural history of and therapeutic options for COVID-19. Treatment with an oral combination of hydroxychloroquine, azithromycin and zinc may represent the best current therapeutic opt..
Sep 5
2020
Synolaki et al., medRxiv, doi:10.1101/2020.09.05.20184655 (Preprint) The Activin/Follistatin-axis is severely deregulated in COVID-19 and independently associated with in-hospital mortality
24% lower mortality [p=0.27]. Retrospective 117 patients, 58 HCQ showing lower mortality for HCQ patients. Version 1 of this paper stated: "HCQ, AZ, [and ...] were found to be independently associated with survival when treatment commenced at FACTCLINYCoD scores ..
Sep 4
2020
Furtado et al., The Lancet, doi:10.1016/S0140-6736(20)31862-6 Azithromycin in addition to standard of care versus standard of care alone in the treatment of patients admitted to the hospital with severe COVID-19 in Brazil (COALITION II): a randomised clinical trial
Small RCT comparing the addition of AZ for very late stage patients on ventilation or oxygen. No significant difference was found, OR 1.36, p=0.11. One notable result is that even within this extremely late stage population, results sugge..
Sep 2
2020
Wang et al., Phytomedicine, doi:10.1016/j.phymed.2020.153333 (In Vitro) Chloroquine and hydroxychloroquine as ACE2 blockers to inhibit viropexis of 2019-nCoV Spike pseudotyped virus
In Vitro study providing novel insights into the molecular mechanism of CQ/HCQ treatment, showing that CQ and HCQ both inhibit the entrance of 2019-nCoV into cells by blocking the binding of the virus with ACE2.
Sep 2
2020
Heras et al., European Geriatric Medicine, doi:10.1007/s41999-020-00432-w (date from earlier preprint) COVID-19 mortality risk factors in older people in a long-term care center
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 2
2020
de la Iglesia et al., medRxiv, doi:10.1101/2020.08.31.20185314 (Preprint) Hydroxicloroquine for pre-exposure prophyylaxis for SARS-CoV-2
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 ..
Sep 1
2020
Hecel et al., Pharmaceuticals, 13:9, 228, doi:10.3390/ph13090228 (Review) Zinc(II)—The Overlooked Éminence Grise of Chloroquine’s Fight against COVID-19?
Review of zinc as an inhibitor of SARS-CoV-2′s RNA-dependent RNA polymerase, and zinc ionophores including CQ/HCQ, showing the latest evidence for zinc and CQ/HCQ having antiviral, and in particular anticoronaviral action.
Sep 1
2020
Elbazidi et al., New Microbes and New Infections, doi:10.1016/j.nmni.2020.100749 Pandemic and social changes, political fate
Analysis of US states and countries. Country analysis shows a significant correlation between the dates of decisions to adopt/decline HCQ, and corresponding trend changes in CFR. US state analysis shows a significant correlation between C..
Aug 30
2020
Albani et al., J, Clinical Medicine, doi:10.3390/jcm9092800 Impact of Azithromycin and/or Hydroxychloroquine on Hospital Mortality in COVID-19
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 29
2020
Castillo et al., Journal of Steroid Biochemistry and Molecular Biology, 203, October 2020, doi:10.1016/j.jsbmb.2020.105751 Effect of calcifediol treatment and best available therapy versus best available therapy on intensive care unit admission and mortality among patients hospitalized for COVID-19: A pilot randomized clinical study
RCT on calcifediol (25-hydroxyvitamin D) treatment for hospitalized COVID-19 patients showing significantly reduced intensive care unit admissions. All patients received standard care including HCQ+AZ. Significantly lower ICU admission wi..
Aug 28
2020
Fried et al., Clinical Infectious Disease, doi:10.1093/cid/ciaa1268 Patient Characteristics and Outcomes of 11,721 Patients with COVID19 Hospitalized Across the United States
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 ..
Aug 27
2020
Ferri at al., Clinical Rheumatology, doi:0.1007/s10067-020-05334-7 COVID-19 and rheumatic autoimmune systemic diseases: report of a large Italian patients series
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..
Aug 26
2020
Fiolet et al., Clinical Microbiology and Infection (meta analysis) Effect of hydroxychloroquine with or without azithromycin on the mortality of COVID-19 patients: a systematic review and meta-analysis
Meta analysis of late stage studies (and one early treatment study with only 2 deaths), showing HCQ RR 0.83 [0.65-1.06], before exclusions RR 0.80 [0.65-1.0]. Authors claim "HCQ alone is not effective", but the result directly c..
Aug 25
2020
Ip et al., BMC Infectious Diseases, doi:10.1186/s12879-021-05773-w (date from earlier preprint) Hydroxychloroquine in the treatment of outpatients with mildly symptomatic COVID-19: A multi-center observational 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 event..
Aug 25
2020
Di Castelnuovo et al., European J. Internal Medicine, doi:10.1016/j.ejim.2020.08.019 Use of hydroxychloroquine in hospitalised COVID-19 patients is associated with reduced mortality: Findings from the observational multicentre Italian CORIST 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 24
2020
Catteau et al., Int. J. Antimicrobial Agents, doi:10.1016/j.ijantimicag.2020.106144 Low-dose Hydroxychloroquine Therapy and Mortality in Hospitalized Patients with COVID-19: A Nationwide Observational Study of 8075 Participants
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 hospi..
Aug 23
2020
Pasquini et al., Journal of Antimicrobial Chemotherapy, doi:10.1093/jac/dkaa321 Effectiveness of remdesivir in patients with COVID-19 under mechanical ventilation in an Italian ICU
16% lower mortality [p=0.34]. Retrospective 51 ICU patients under mechanical ventilation, 33 treated with HCQ, showing unadjusted lower mortality with treatment.
Aug 21
2020
Ly et al., International Journal of Antimicrobial Agents, doi:10.1016/j.ijantimicag.2020.106219 (date from earlier preprint) Pattern of SARS-CoV-2 infection among dependant elderly residents living in retirement homes in Marseille, France, March-June 2020
56% lower mortality [p=0.02]. Retrospective analysis of retirement homes, HCQ+AZ >= 3 days mortality OR 0.37, p=0.02. 1690 elderly residents (mean age 83), 226 infected residents, 116 treated with HCQ+AZ >= 3 days. Detection via mass screening also showed significant ..
Aug 21
2020
Lane et al., The Lancet Rheumatology, doi:10.1016/S2665-9913(20)30276-9 Risk of hydroxychloroquine alone and in combination with azithromycin in the treatment of rheumatoid arthritis: a multinational, retrospective study
Retrospective study of RA patients using HCQ vs. sulfasalazine (another DMARD). HCQ treatment showed no increased risk in the short term (up to 30 days) among patients with RA. Long term use was associated with excess cardiovascular morta..
Aug 21
2020
Gonzalez et al., medRxiv, doi:10.1101/2020.08.18.20172874 (Preprint) The Prognostic Value of Eosinophil Recovery in COVID-19: A Multicentre, Retrospective Cohort Study on Patients Hospitalised in Spanish Hospitals
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 conf..
Aug 20
2020
Dubernet et al., J. Global Antimicrobial Resistance, doi:10.1016/j.jgar.2020.08.001 A comprehensive strategy for the early treatment of COVID-19 with azithromycin/hydroxychloroquine and/or corticosteroids: results of a retrospective observational study in the French overseas department of Reunion Island
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 wit..
Aug 20
2020
Prodromos, C., New Microbes and New Infections, doi:10.1016/j.nmni.2020.100747 Hydroxychloroquine is protective to the heart, not harmful: A systematic review
Review concluding that HCQ/AZ does not cause Torsade de Pointes or related deaths, HCQ decreases cardiac events, and HCQ should not be restricted in use for COVID-19 patients because of fear of cardiac mortality.
Aug 18
2020
Pinato et al., Cancer Discovery, doi:10.1158/2159-8290.CD-20-0773 Clinical portrait of the SARS-CoV-2 epidemic in European cancer patients
59% lower mortality [p=0.0001]. Restrospective 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. Potent..
Aug 15
2020
Peters et al., Clinical Microbiology and Infection, doi:10.1016/j.cmi.2020.10.004 (date from earlier preprint) Outcomes of Persons With COVID-19 in Hospitals With and Without Standard Treatment With (Hydroxy)chloroquine
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 or dexamethasone. Late stage (admitted to hospital with positive test or CT scan abnormalities). 4 of 7 hospitals..
Aug 14
2020
Abd-Elsalam et al., American Journal of Tropical Medicine and Hygiene, doi:10.4269/ajtmh.20-0873 Hydroxychloroquine in the Treatment of COVID-19: A Multicenter Randomized Controlled Study
20% higher mortality [p=1] and 30% improved recovery [p=0.009]. Small RCT in Egypt with 97/97 HCQ/control patients, showing 58% more recovery @28days for HCQ (53.6% HCQ, 34% control), p=0.009 (0.06 in the paper refers to the 5 combined recovery/death/ICU values). No significant difference in ventilati..
Aug 13
2020
Roomi et al., J. Medical Internet Research, doi:10.2196/21758 Efficacy of hydroxychloroquine and tocilizumab in patients with COVID-19: A single-center retrospective chart review
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 12
2020
Pablos et al., Annals of the Rheumatic Diseases, doi:10.1136/annrheumdis-2020-218296 Clinical outcomes of hospitalised patients with COVID-19 and chronic inflammatory and autoimmune rheumatic diseases: a multicentric matched cohort 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 11
2020
Tarek et al., European Journal of Drug Metabolism and Pharmacokinetics, doi:10.1007/s13318-020-00640-6 Pharmacokinetic Basis of the Hydroxychloroquine Response in COVID-19: Implications for Therapy and Prevention
In Silico analysis of HCQ treatment showing concluding that HCQ may affect viral clearance if administered early enough when the virus is still confined to the pharyngeal cavity; HCQ's effects against SARS-CoV-2 might be exerted more thro..
Aug 11
2020
Bakhshaliyev et al., J. Electrocardiology, doi:10.1016/j.jelectrocard.2020.08.008 The effect of 5-day course of hydroxychloroquine and azithromycin combination on QT interval in non-ICU COVID19(+) patient
Safety study of 109 patients showing 5 days of HCQ+AZ did not lead to clinically significant QT prolongation or other conduction delays compared to baseline ECG in non-ICU patients.
Aug 11
2020
Saleemi et al., medRxiv, doi:10.1101/2020.08.05.20151027 (Preprint) Time to negative PCR from symptom onset in COVID-19 patients on Hydroxychloroquine and Azithromycin - A real world experience
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 comorbidi..
Aug 8
2020
Lopez et al., Int. J. Antimicrob. Agents, doi:/j.ijantimicag.2020.106136 Effects of Hydroxychloroquine on Covid-19 in Intensive Care Unit Patients: Preliminary Results
Small retrospective study of 29 ICU patients comparing those with HCQ plasma concentration within target to those with a concentration below the target value, with no significant differences found. Mortality in the on-target group was 0% ..
Aug 6
2020
Salvarani et al., Arthritis & Rheumatology, doi:10.1002/art.41475 Susceptibility to COVID‐19 in Patients Treated With Antimalarials: A Population‐Based Study in Emilia‐Romagna, Northern Italy
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..
Aug 6
2020
McCullough et al., The American Journal of Medicine, doi:10.1016/j.amjmed.2020.07.003 (Review) Pathophysiological Basis and Rationale for Early Outpatient Treatment of SARS-CoV-2 (COVID-19) Infection
Review of pathophysiological principles related to early outpatient treatment and therapeutic approaches including reduction of reinoculation, combination antiviral therapy, immunomodulation, antiplatelet/antithrombotic therapy, and admin..
Aug 6
2020
Watanabe et al., Open Letter (Letter) (meta analysis) Concerns regarding the misinterpretation of statistical hypothesis testing in clinical trials for COVID-19
Open letter signed by 38 professors and doctors regarding misinterpretation of statistics in HCQ RCTs. Authors note [veja.abril.com.br] that data from RCTs for early treatment in outpatients to date actually show favorable effects, especi..
Aug 5
2020
Singer et al., Annals of the Rheumatic Diseases, doi:10.1136/annrheumdis-2020-218500 (Letter) Hydroxychloroquine ineffective for COVID-19 prophylaxis in lupus and rheumatoid arthritis
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 informati..
Aug 5
2020
Kalligeros et al., Journal of Global Antimicrobial Resistance, doi:10.1016/j.jgar.2020.07.018 Hydroxychloroquine use in hospitalised patients with COVID-19: An observational matched cohort 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 4
2020
Kamran et al., medRxiv, doi:10.1101/2020.07.30.20165365 (Preprint) Clearing the fog: Is HCQ effective in reducing COVID-19 progression: A randomized controlled trial
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 ..
Aug 3
2020
Berenguer et al., Clinical Microbiology and Infection, doi:10.1016/j.cmi.2020.07.024 Characteristics and predictors of death among 4035 consecutively hospitalized patients with COVID-19 in Spain
18% lower mortality [p=0.0001]. Retrospective 4035 hospitalized patients in Spain showing reduced mortality with HCQ (data is in the supplementary appendix).
Aug 3
2020
Yu et al., Science China Life Sciences, 2020 Aug 3, doi:10.1007/s11427-020-1782-1 (Letter) Beneficial effects exerted by hydroxychloroquine in treating COVID-19 patients via protecting multiple organs
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..
Aug 2
2020
Davido et al., Int. J. Antimicrobial Agents, 2020, doi:10.1016/j.ijantimicag.2020.106129 Impact of medical care including anti-infective agents use on the prognosis of COVID-19 hospitalized patients over time
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 admiss..
Aug 2
2020
Sheaff, R., bioRxiv, doi:10.1101/2020.08.02.232892 (Preprint) (In Vitro) A New Model of SARS-CoV-2 Infection Based on (Hydroxy)Chloroquine Activity
In Vitro study presenting a new theory on SARS-CoV-2 infection and why HCQ/CQ provides benefits, which potentially explains the observed relationships with smoking, diabetes, obesity, age, and treatment delay, and confirms the importance ..
Aug 1
2020
Bernabeu-Wittel et al., J. Gerontol. A Biol. Sci. Med. Sci., doi:10.1093/gerona/glaa192 Effectiveness of a On-Site Medicalization Program for Nursing Homes with COVID-19 Outbreaks
59% lower mortality [p=0.03]. 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 depen..
Jul 31
2020
Mazzitelli et al., Travel Medicine and Infectious Disease, 37, doi:10.1016/j.tmaid.2020.101826 (Letter) Apparent inefficacy of hydroxychloroquine combined with azithromycin on SARS-CoV-2 clearance in an incident cohort of geriatric patients with COVID-19
Report on HCQ+AZ use in 41 elderly high-risk patients. 29 of 30 patients with treatment >= 5 days survived. Only 10% were PCR negative after one week, however the Ct value is not specified.
Jul 29
2020
D'Arminio Monforte et al., Int. J. Infectious Diseases, doi:10.1016/j.ijid.2020.07.056 (Letter) Effectiveness of Hydroxychloroquine in COVID-19 disease: A done and dusted situation?
34% lower mortality [p=0.12]. HCQ+AZ adjusted death HR 0.44, p=0.009. Propensity scores include baseline COVID-19 disease severity, age, gender, number of comorbidities, cardio-vascular disease, duration of symptoms, date of admission, baseline plasma CRP. IPW censori..
Jul 28
2020
BaŞaran et al., Turk. J. Med. Sci., doi:10.3906/sag-2006-173 Outcome of Non-Critical COVID-19 Patients with Early Hospitalization and Early Antiviral Treatment Outside the ICU
Observational study of 174 hospitalized patients in Turkey, median age 45.4, 23 treated with HCQ, 113 with HCQ+AZ, and 32 with regimens including favipiravir. 75% reduction in the median time to clinical improvement for HCQ+AZ vs. FAV, RR..
Jul 27
2020
Santos et al., Clinical Rheumatology, doi:10.1007/s10067-020-05301-2 Determinants of COVID-19 disease severity in patients with underlying rheumatic disease
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.
Jul 26
2020
Mitjà et al., NEJM, doi:10.1056/NEJMoa2021801 (date from earlier preprint) A Cluster-Randomized Trial of Hydroxychloroquine as Prevention of Covid-19 Transmission and Disease
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 o..
Jul 24
2020
Khurana et al., medRxiv, doi:10.1101/2020.07.21.20159301 (Preprint) Prevalence and clinical correlates of COVID-19 outbreak among healthcare workers in a tertiary level hospital
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 stu..
Jul 23
2020
Cavalcanti et al., NEJM, July 23, 2020, doi:10.1056/NEJMoa2019014 Hydroxychloroquine with or without Azithromycin in Mild-to-Moderate Covid-19
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 def..
Jul 22
2020
Kadnur et al., Journal of Family Medicine and Primary Care, doi:10.4103/jfmpc.jfmpc_1177_21 Hydroxychloroquine pre-exposure prophylaxis for COVID-19 among healthcare workers: Initial experience from India
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 addition..
Jul 22
2020
Ou et al., PLOS Pathogens, doi:10.1371/journal.ppat.1009212 (date from earlier preprint) (In Vitro) Hydroxychloroquine-mediated inhibition of SARS-CoV-2 entry is attenuated by TMPRSS2
In Vitro analysis showing that HCQ efficiently blocks viral entry mediated by cathepsin L, but not by TMPRSS2, and that a combination of HCQ and a TMPRSS2 inhibitor prevents SARS-CoV-2 infection more potently than either drug alone.
Jul 22
2020
Hoffmann et al., Nature, (2020), doi:10.1038/s41586-020-2575-3 (In Vitro) Chloroquine does not inhibit infection of human lung cells with SARS-CoV-2
The title of this paper does not appear to match the results. Fig. 1b @100uM shows CQ results in a ~4.5 fold decrease (on a linear scale) in extracellular virus, p=0.05, after 24 hours (we do not see the supplementary data at this time so..
Jul 22
2020
Rivera et al., Cancer Discovery, doi:10.1158/2159-8290.CD-20-0941 Utilization of COVID-19 Treatments and Clinical Outcomes among Patients with Cancer: A COVID-19 and Cancer Consortium (CCC19) Cohort 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 indicatio..
Jul 22
2020
Kelly et al., British Journal of Clinical Pharmacology, doi:10.1111/bcp.14482 Clinical outcomes and adverse events in patients hospitalised with COVID‐19, treated with off‐label hydroxychloroquine and azithromycin
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 confounde..
Jul 21
2020
Bernaola et al., medRxiv, doi:10.1101/2020.07.17.20155960 (Preprint) Observational Study of the Efficiency of Treatments in Patients Hospitalized with Covid-19 in Madrid
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 20
2020
Krishnan et al., J Clin Anesth., doi:10.1016/j.jclinane.2020.110005 Clinical comorbidities, characteristics, and outcomes of mechanically ventilated patients in the State of Michigan with SARS-CoV-2 pneumonia
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 20
2020
Desbois et al., Research Square, doi:10.21203/rs.3.rs-41653/v1 (Preprint) Prevalence and clinical features of COVID-19 in a large cohort of 199 patients with sarcoidosis
17% fewer cases [p=1]. Retrospective 199 sarcoidosis patients showing non-statistically significant HCQ RR 0.83, p=1.0.
Jul 20
2020
Risch, H., American Journal of Epidemiology, July 20, 2020, doi:10.1093/aje/kwaa152 (meta analysis) Response to: “Early Outpatient Treatment of Symptomatic, High-Risk Covid-19 Patients” and “Re: Early Outpatient Treatment of Symptomatic, High-Risk Covid-19 Patients that Should be Ramped-Up Immediately as Key to the Pandemic Crisis”
Updated meta analysis including 7 new studies of high-risk outpatients, for a total of 12 studies, all showing significant benefit.
Jul 18
2020
Watanabe, M., arXiv.org, arXiv:2007.09477 (Preprint) (meta analysis) Efficacy of Hydroxychloroquine as Prophylaxis for Covid-19
Secondary analysis of Boulware et al.'s PEP trial and treatment delay-response data, confirming that HCQ is effective when used early, p<0.01. The effectiveness found is especially notable considering the limitations of the study. Treatme..
Jul 19
2020
McGrail et al., medRxiv, doi:10.1101/2020.07.17.20156521 (Preprint) COVID-19 Case Series at UnityPoint Health St. Luke’s Hospital in Cedar Rapids, IA
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 tre..
Jul 17
2020
Lyngbakken et al., Nature Communications, doi:10.1038/s41467-020-19056-6 A pragmatic randomized controlled trial reports lack of efficacy of hydroxychloroquine on coronavirus disease 2019 viral kinetics
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 signi..
Jul 16
2020
Hong et al., Infect. Chemother., 2020, doi:10.3947/ic.2020.52.e43 Early Hydroxychloroquine Administration for Rapid Severe Acute Respiratory Syndrome Coronavirus 2 Eradication
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 administrat..
Jul 16
2020
Skipper et al., Annals of Internal Medicine, doi:10.7326/M20-4207 Hydroxychloroquine in Nonhospitalized Adults With Early COVID-19: A Randomized Trial
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 i..
Jul 16
2020
Mitjà et al., Clinical Infectious Diseases, ciaa1009, doi:10.1093/cid/ciaa1009 Hydroxychloroquine for Early Treatment of Adults with Mild Covid-19: A Randomized-Controlled Trial
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 co..
Jul 15
2020
Gupta et al., JAMA Intern. Med., doi:10.1001/jamainternmed.2020.3596 Factors Associated With Death in Critically Ill Patients With Coronavirus Disease 2019 in the US
6% higher mortality [p=0.41]. Analysis of 2215 intensive care unit patients showing no significant differences with this very late stage use of HCQ. HCQ+AZ mortality relative risk RR 0.96, p=0.53, HCQ and HCQ+AZ combined RR 1.06, p=0.409.
Jul 15
2020
Kavanagh et al., Med. Hypotheses, doi:10.1016/j.mehy.2020.110110 Inhaled hydroxychloroquine to improve efficacy and reduce harm in the treatment of COVID-19
Proposal to use an inhaled formulation of HCQ which has passed safety studies in clinical trials for the treatment of asthma. Authors advocate for early treatment or prophylaxis of COVID-19, using HCQ as an inhaled aerosol, to deliver the..
Jul 14
2020
Trullàs et al., Research Square, doi:10.21203/rs.3.rs-39421/v1 (Preprint) High in-hospital mortality due to COVID-19 in a community hospital in Spain: a prospective observational study
36% lower mortality [p=0.12]. Retrospective 100 hospitalized patients in Spain showing lower mortality with HCQ+AZ.
Jul 14
2020
Chowdhury et al., Eurasian Journal of Medicine and Oncology, doi:10.14744/ejmo.2021.16263 A Randomized Trial of Ivermectin-Doxycycline and Hydroxychloroquine-Azithromycin therapy on COVID19 patients
Small 116 patient RCT comparing ivermectin+doxycycline and HCQ+AZ, not showing a significant difference in time to PCR negative or symptom resolution. Time to symptomatic recovery was 5.93 days for ivermectin+doxycycline vs. 6.99 days for..
Jul 11
2020
Lecronier et al., Critical Care, 24:418, 2020, doi:10.1186/s13054-020-03117-9 Comparison of hydroxychloroquine, lopinavir/ritonavir, and standard of care in critically ill patients with SARS-CoV-2 pneumonia: an opportunistic retrospective analysis
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..
Jul 10
2020
Cravedi et al., American Journal of Transplantation, doi:10.1111/ajt.16185 COVID-19 and kidney transplantation: Results from the TANGO International Transplant Consortium
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 10
2020
Chen et al., PLoS ONE, doi:10.1371/journal.pone.0242763 A Multicenter, randomized, open-label, controlled trial to evaluate the efficacy and tolerability of hydroxychloroquine and a retrospective study in adult patients with mild to moderate Coronavirus disease 2019 (COVID-19)
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,..
Jul 9
2020
Rivera-Izquierdo et al., Medicina Clínica, doi:10.1016/j.medcli.2020.06.025 Agentes terapéuticos utilizados en 238 pacientes hospitalizados por COVID-19 y su relación con la mortalidad
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 9
2020
Raoult et al., Preprint (Preprint) (meta analysis) Hydroxychloroquine and Azithromycin as a Treatment of COVID-19: Results of an Open-Label Non-Randomized Clinical Trial: Response to David Spencer (Elsevier)
Updated meta analysis showing significant reductions in mortality and viral shedding. Mortality OR 0.53 [0.4-0.71] for clinical studies, 0.92 big data studies, 18,211 patients. Persistent viral shedding OR 0.47 [0.28-0.79], 4,540 patients.
Jul 8
2020
Marzolini et al., Antimicrobial Agents and Chemotherapy, doi:10.1128/AAC.01177-20 Effect of Systemic Inflammatory Response to SARS-CoV-2 on Lopinavir and Hydroxychloroquine Plasma Concentrations
Study of Lopinivar and HCQ plasma concentrations and CRP levels in late stage (treatment initiation median 8 days from onset) COVID-19 patients. The median HCQ plasma concentration was 171 ng/ml, which authors suggest indicates that HCQ l..
Jul 8
2020
Li et al., Cell Death & Disease volume 11, doi:10.1038/s41419-020-2721-8 (Review) Is hydroxychloroquine beneficial for COVID-19 patients?
Review of the anti-inflammatory, antiviral, and protective vascular effects of CQ and HCQ, noting that HCQ may be preferable for COVID-19 due to fewer side effects.
Jul 7
2020
Goldstein, L., Preprint, July 7, 2020 (Review) (Preprint) Hydroxychloroquine-based COVID-19 Treatment, A Systematic Review of Clinical Evidence and Expert Opinion from Physicians’ Surveys
85% of globally surveyed physicians recognized HCQ as at least partially effective in treating COVID-19, according to Sermo W3. More than half of the surveyed US physicians would take the drug or give it to family members early or even be..
Jul 7
2020
An et al., medRxiv, doi:10.1101/2020.07.04.20146548 (Preprint) Treatment Response to Hydroxychloroquine and Antibiotics for mild to moderate COVID-19: a retrospective cohort study from South Korea
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 tha..
Jul 3
2020
Derwand et al., International Journal of Antimicrobial Agents, doi:10.1016/j.ijantimicag.2020.106214 (date from earlier preprint) COVID-19 Outpatients – Early Risk-Stratified Treatment with Zinc Plus Low Dose Hydroxychloroquine and Azithromycin: A Retrospective Case Series 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 3
2020
Zhong et al., Lancent Rheumatology, doi:10.1016/S2665-9913(20)30227-7 COVID-19 in patients with rheumatic disease in Hubei province, China: a multicentre retrospective observational 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 othe..
Jul 1
2020
Arshad et al., Int. J. Infect. Dis., July 1 2020, doi:10.1016/j.ijid.2020.06.099 Treatment with Hydroxychloroquine, Azithromycin, and Combination in Patients Hospitalized with COVID-19
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 percenta..
Jul 1
2020
Samuel et al., Heart Rhythm, doi:10.1016/j.hrthm.2020.06.033 Incidence of arrhythmias and electrocardiographic abnormalities in symptomatic pediatric patients with PCR positive SARS-CoV-2 infection including drug induced changes in the corrected QT interval (QTc)
In pediatric patients with PCR positive active COVID-19 infection, significant arrhythmias are infrequent, but occur at an incidence higher than expected in a general pediatric population. Comorbidities are not more common in patients wit..
Jun 30
2020
Martinez-Lopez et al., Blood Cancer Journal, doi:10.1038/s41408-020-00372-5 Multiple Myeloma and SARS-CoV-2 Infection: Clinical Characteristics and Prognostic Factors of Inpatient Mortality
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 30
2020
Mikami et al., J. Gen. Intern. Med., doi:10.1007/s11606-020-05983-z Risk Factors for Mortality in Patients with COVID-19 in New York City
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 30
2020
Komissarov et al., medRxiv, doi:10.1101/2020.06.30.20143289 (Preprint) Hydroxychloroquine has no effect on SARS-CoV-2 load in nasopharynx of patients with mild form of COVID-19
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 signi..
Jun 29
2020
Sosa-García et al., Cir Cir. 2020, 88:5, 569-575, doi:10.24875/CIRU.20000675 Experience in the management of severe COVID-19 patients in an intensive care unit
11% higher mortality [p=1]. Small retrospective study of 56 ICU patients in Mexico showing HCQ RR 1.1, p = 1.0.
Jun 29
2020
Ferreira et al., J. Medical Virology, July 9, 2020, doi:10.1002/jmv.26286 (date from earlier preprint) Chronic treatment with hydroxychloroquine and SARS-CoV-2 infection
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 ..
Jun 29
2020
Mfeukeu-Kuate et al. (Preprint) Electrocardiographic safety of daily Hydroxychloroquine 400mg plus Azithromycin 250mg as an ambulatory treatment for COVID-19 patients in Cameroon
No life-threatening modifications of the QT interval was observed in non-severe COVID-19 patients treated ambulatory with HCQ+AZ. 51 relatively young patients 39 +/- 11.
Jun 25
2020
Gendebien et al., Annals of the Rheumatic Diseases, doi:10.1136/annrheumdis-2020-218244 (Letter) Systematic analysis of COVID-19 infection and symptoms in a systemic lupus erythematosus population: correlation with disease characteristics, hydroxychloroquine use and immunosuppressive treatments
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..
Jun 25
2020
Lagier et al., Travel Med. Infect. Dis. 101791, Jun 25, 2020, doi:10.1016/j.tmaid.2020.101791 Outcomes of 3,737 COVID-19 patients treated with hydroxychloroquine/azithromycin and other regimens in Marseille, France: A retrospective analysis
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 23
2020
Bousquet et al., Aging, 12:12, 11306-11313, doi:10.18632/aging.103583 ADL-dependency, D-Dimers, LDH and absence of anticoagulation are independently associated with one-month mortality in older inpatients with Covid-19
43% lower mortality [p=0.15]. Observational prospective 108 hospitalized patients 65 and older, showing HCQ mortality OR 0.49, p = 0.15.
Jun 22
2020
Isaksen et al., medRxiv, doi:10.1101/2020.06.19.20135475 (Preprint) Chloroquine, but not hydroxychlorquine, prolongs the QT interval in a primary care population
Safety analysis in patients without COVID-19, finding a small increase in QTc associated with use of CQ, but not HCQ. Authors also study mortality (n=3,368), with HCQ hazard ratio 0.67 [0.43-1.05].
Jun 22
2020
Fontana et al., Clinical Kidney Journal, 13:3, 334–339, doi:10.1093/ckj/sfaa084 SARS-CoV-2 infection in dialysis patients in northern Italy: a single-centre experience
50% lower mortality [p=0.53]. Very small observational study of 15 dialysis patients showing HCQ mortality RR 0.50, p = 0.53.
Jun 22
2020
Chen et al., medRxiv, doi:10.1101/2020.06.19.20136093 (Preprint) Efficacy and safety of chloroquine or hydroxychloroquine in moderate type of COVID-19: a prospective open-label randomized controlled study
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 21
2020
Faíco-Filho et al., Braz J Microbiol, doi:10.1007/s42770-020-00395-x (date from earlier preprint) No benefit of hydroxychloroquine on SARS-CoV-2 viral load reduction in non-critical hospitalized patients with COVID-19
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..
Jun 19
2020
SMSH Sawai Man Singh Hospital, India (News) HCQ beneficial as preventive drug: SMS doctors told ICMR
PrEP with 4,300 very high risk healthcare workers in a hospital with up to 500+ COVID patients at a time, only 1% cases, all recovered.
Jun 19
2020
NIH, study not available yet (News) NIH halts clinical trial of hydroxychloroquine
NIH halts late stage trial reporting no harm and no benefit. 470 patients.
Jun 19
2020
Sbidian et al., medRxiv, doi:10.1101/2020.06.16.20132597 (Preprint) 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
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. Oth..
Jun 19
2020
Kaptein et al., bioRxiv, doi:10.1101/2020.06.19.159053 Favipiravir at high doses has potent antiviral activity in SARS-CoV-2−infected hamsters, whereas hydroxychloroquine lacks activity
Animal study with Syrian hamsters, showing treatment of SARS-CoV-2-infected hamsters with favipiravir or HCQ (with and without AZ). Treatment with HCQ alone resulted in a very modest reduction of 0.3 log10 viral RNA copies/mg lung, and no..
Jun 18
2020
Paccoud et al., Clinical Infectious Diseases, doi:10.1093/cid/ciaa791 Compassionate use of hydroxychloroquine in clinical practice for patients with mild to severe Covid-19 in a French university hospital
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 17
2020
Capucci et al., J. Cardiovasc. Med. 21, 922–923, doi:10.2459/JCM.0000000000001061 Low hospitalization rate without severe arrhythmias: a prospective survey on 350 patients early home treated with hydroxychloroquine during COVID-19 pandemic
Prospective analysis of early treatment of 350 patients in Italy (without waiting for PCR results), showing low hospitalization rates and no serious adverse events. From 274 patients treated with HCQ, 16 required hospitalization (5.8%). M..
Jun 17
2020
Xue et al., J. Med. Virology, June 17, 2020, doi:10.1002/jmv.26193 Hydroxychloroquine treatment in COVID-19: a descriptive observational analysis of 30 cases from a single center in Wuhan, China
30 hospitalized patients. Early use of HCQ is more effective, 43% reduction in progression from moderate to severe. "Early" is relative here, within 7 days of hospitalization.
Jun 17
2020
Luo et al., Annals of Oncology, 31:10, 1386-1396, doi:10.1016/j.annonc.2020.06.007 COVID-19 in patients with lung cancer
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 16
2020
Kim et al., Korean J Intern Med, doi:10.3904/kjim.2020.224 Lopinavir-ritonavir versus hydroxychloroquine for viral clearance and clinical improvement in patients with mild to moderate coronavirus disease 2019
Small retrospective study of hospitalized patients with 31 lopinavir-ritonavir and 34 HCQ patients, HCQ 400mg once per day, finding no significant difference in clinical response, but more rapid viral clearance with lopinavir-ritonavir.
Jun 16
2020
Huang et al., Annals of the Rheumatic Diseases 2020:79, 1163-1169, doi:10.1136/annrheumdis-2020-217425 Clinical characteristics of 17 patients with COVID-19 and systemic autoimmune diseases: a retrospective 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 12
2020
Scherrmann, AAPS J 22, 86 (2020), doi:10.1208/s12248-020-00465-w (Theory) Intracellular ABCB1 as a Possible Mechanism to Explain the Synergistic Effect of Hydroxychloroquine-Azithromycin Combination in COVID-19 Therapy
Proposes a new mechanism supporting the synergistic interaction between HCQ+AZ.
Jun 12
2020
Giacomelli et al., Journal of Medical Virology, doi:10.1002/jmv.26407 (date from earlier preprint) Early administration of lopinavir/ritonavir plus hydroxychloroquine does not alter the clinical course of SARS-CoV-2 infection: a retrospective cohort study
Late stage study of hospitalized patients comparing treatment starting within 5 days versus later. Note that "early" here is only relative - all patients are hospitalized so this is "late" and "very late". Th..
Jun 10
2020
Wang et al., medRxiv, doi:10.1101/2020.06.11.20128926 (Preprint) Comorbidity and Sociodemographic determinants in COVID-19 Mortality in an US Urban Healthcare System
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 10
2020
Otea et al., medRxiv, doi:10.1101/2020.06.10.20101105 (Preprint) A short therapeutic regimen based on hydroxychloroquine plus azithromycin for the treatment of COVID-19 in patients with non-severe disease. A strategy associated with a reduction in hospital admissions and complications.
80 moderate cases, HCQ+AZ appears to reduce serious complications and death. Moderate treated cases resulted in hospitalization at the same rate as mild untreated cases suggesting efficacy.
Jun 9
2020
Pirnay et al., Hosp. Pharm. and Clinician, doi:10.1016/j.phclin.2020.06.001 Beneficial effect of Hydroxychloroquine-Azithromycin combination in the treatment of elderly patients with Covid-19: results of an observational study
68 very high risk nursing home residents, median age 86, HCQ+AZ early treatment within 2.5 days onset, 2 stopped due to QTc. Only 7 died, significantly less than other nursing homes in France and the same as the median death for the same ..
Jun 9
2020
Bhattacharya et al., medRxix, doi:10.1101/2020.06.09.20116806 (Preprint) Pre exposure Hydroxychloroquine use is associated with reduced COVID19 risk in healthcare workers
81% fewer cases [p=0.001]. HCQ reduced cases from 38% to 7%. 106 people. No serious adverse effects.
Jun 6
2020
Roussel et al., New Microbes and New Infections, Volume 38, doi:10.1016/j.nmni.2020.100710 (Review) Influence of conflicts of interest on public positions in the COVID-19 era, the case of Gilead Sciences
Shows a correlation (Spearman test, p = 0.017) between the amount received from Gilead Sciences and public opposition to the use of HCQ in France.
Jun 6
2020
Million et al., New Microbes and New Infections, doi:10.1016/j.nmni.2020.100709 (meta analysis) Clinical Efficacy of Chloroquine derivatives in COVID-19 Infection: Comparative metaanalysis between the Big data and the real world
[H]CQ effective and reduces mortality by a factor 3. Meta analysis of 20 studies.
Jun 5
2020
RECOVERY Collaborative Group, NEJM, doi:10.1056/NEJMoa2022926 (press release 6/5) (Preprint) Effect of Hydroxychloroquine in Hospitalized Patients with COVID-19: Preliminary results from a multi-centre, randomized, controlled trial
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..
Jun 3
2020
Boulware et al., NEJM, June 3 2020, doi:10.1056/NEJMoa2016638 A Randomized Trial of Hydroxychloroquine as Postexposure Prophylaxis for Covid-19
17% fewer cases [p=0.35]. Remote post-exposure prophylaxis RCT reporting "[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 incorr..
Jun 1
2020
Al-Kofahi et al., Clin. Pharmacol. Ther., Jun 1, 2020, doi:10.1002/cpt.1874 Finding the Dose for Hydroxychloroquine Prophylaxis for COVID‐19: The Desperate Search for Effectiveness
Analysis of HCQ dosing regimens, recommending: PrEP: 800mg loading dose followed by 400mg 2 or 3 times weekly to maintain weekly troughs above EC50 in >50% of patients at steady-state. PEP: 800mg loading dose followed in 6 hours by 600mg,..
May 31
2020
Guérin et al., Asian J. Medicine and Health, July 15, 2020, doi:10.9734/ajmah/2020/v18i730224 (date from earlier preprint) Azithromycin and Hydroxychloroquine Accelerate Recovery of Outpatients with Mild/Moderate COVID-19
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 29
2020
Rogado et al., Lung Cancer, doi:10.1016/j.lungcan.2020.05.034 Covid-19 and lung cancer: A greater fatality rate?
92% lower mortality [p=0.02]. Retrospective 17 hospitalized lung cancer patients showing lower mortality with HCQ+AZ treatment.
May 28
2020
Chamieh et al., medRxiv 2020.05.28.20114835, doi:10.1101/2020.05.28.20114835 (Preprint) Viral Dynamics Matter in COVID-19 Pneumonia: the success of early treatment with hydroxychloroquine and azithromycin in Lebanon
HCQ+AZ potentially explains 94.7% success in treating a fairly complex cohort.
May 28
2020
Chatterjee et al., Indian J. Med. Res., June 20, 2020, doi:10.4103/ijmr.IJMR_2234_20 Healthcare workers & SARS-CoV-2 infection in India: A case-control investigation in the time of COVID-19
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 28
2020
Huang et al., National Science Review, nwaa113, doi:10.1093/nsr/nwaa113 Preliminary evidence from a multicenter prospective observational study of the safety and efficacy of chloroquine for the treatment of COVID-19
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 27
2020
Goldman et al., NEJM, doi:10.1056/NEJMoa2015301 Remdesivir for 5 or 10 Days in Patients with Severe Covid-19
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 28
2020
Kuderer et al., Lancet, June 20, 2020, doi:10.1016/S0140-6736(20)31187-9 (date from earlier preprint) Clinical impact of COVID-19 on patients with cancer (CCC19): a cohort 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 migh..
May 28
2020
Gianfrancesco et al., Annals of the Rheumatic Diseases, 79:7, 859-866, doi:10.1136/annrheumdis-2020-217871 Characteristics associated with hospitalisation for COVID-19 in people with rheumatic disease: data from the COVID-19 Global Rheumatology Alliance physician-reported registry
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 27
2020
Risch, American Journal of Epidemiology, kwaa093, 27 May 2020, doi:10.1093/aje/kwaa093 (meta analysis) Early Outpatient Treatment of Symptomatic, High-Risk Covid-19 Patients that Should be Ramped-Up Immediately as Key to the Pandemic Crisis
Five studies, including two controlled clinical trials, have demonstrated significant outpatient treatment efficacy.
May 25
2020
Ip et al., PLoS ONE, doi:10.1371/journal.pone.0237693 Hydroxychloroquine and Tocilizumab Therapy in COVID-19 Patients - An Observational 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 ..
May 24
2020
Hraiech et al., Ann. Intensive Care, doi:10.1186/s13613-020-00678-4 Lack of viral clearance by the combination of hydroxychloroquine and azithromycin or lopinavir and ritonavir in SARS-CoV-2-related acute respiratory distress syndrome
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 22
2020
ICMR, Indian Council of Medical Research (Advisory) Revised advisory on the use of Hydroxychloroquine (HCQ) as prophylaxis for SARS-CoV-2 infection
Healthcare workers on HCQ prophylaxis less likely to get COVID. Significant dose-response relationship. Extends recommended HCQ prophylaxis to asymptomatic household contacts of cases and frontline workers. Degree of benefit not quantified.
May 22
2020
Mehra et al., The Lancet, May 22, 2020, doi: 10.1016/S0140-6736(20)31180-6 Hydroxychloroquine or chloroquine with or without a macrolide for treatment of COVID-19: a multinational registry analysis
Incorrect at first read (implausible death, ventilation, and population numbers). This paper was retracted.
May 21
2020
Luo et al., The American Journal of Tropical Medicine and Hygiene, doi:10.4269/ajtmh.20-0375 Metformin Treatment Was Associated with Decreased Mortality in COVID-19 Patients with Diabetes in a Retrospective Analysis
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 19
2020
Singh et al., medRxiv, doi:10.1101/2020.05.12.20099028 (Preprint) Outcomes of Hydroxychloroquine Treatment Among Hospitalized COVID-19 Patients in the United States- Real-World Evidence From a Federated Electronic Medical Record Network
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 indic..
May 18
2020
Kim et al., medRxiv, doi:10.1101/2020.05.13.20094193 (Preprint) Treatment Response to Hydroxychloroquine, Lopinavir/Ritonavir, and Antibiotics for Moderate COVID 19: A First Report on the Pharmacological Outcomes from South Korea
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 18
2020
Ahmad et al., doi:10.1101/2020.05.18.20066902 (Preprint) Doxycycline and Hydroxychloroquine as Treatment for High-Risk COVID-19 Patients: Experience from Case Series of 54 Patients in Long-Term Care Facilities
54 patients in long term care facilities. 6% death with HCQ+AZ compared to 22% using a naive indirect comparison.
May 16
2020
Macias et al., medRxiv, 10.1101/2020.05.16.20104141 (Preprint) Similar incidence of Coronavirus Disease 2019 (COVID-19) in patients with rheumatic diseases with and without hydroxychloroquine therapy
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. ..
May 15
2020
Yu et al., Science China Life Sciences, 2020 May 15, 1-7, doi:10.1007/s11427-020-1732-2 Low Dose of Hydroxychloroquine Reduces Fatality of Critically Ill Patients With COVID-19
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 treatm..
May 14
2020
Mahévas et al., BMJ 2020, 369, doi: https://doi.org/10.1136/bmj.m1844 Clinical efficacy of hydroxychloroquine in patients with covid-19 pneumonia who require oxygen: observational comparative study using routine care data
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..
May 13
2020
Okour et al., Journal of Pharmacokinetics and Pharmacodynamics, May 13, 2020, doi:10.1007/s10928-020-09689-x Hydroxychloroquine and azithromycin as potential treatments for COVID-19; clinical status impacts the outcome
Odds of PCR-positive decrease by 53% for each unit increase in HCQ log-concentration. Similarly, the odds decrease by 61%, and by 12% for each day increase, and for azithromycin co-treatment, respectively. Computes the minimum HCQ concent..
May 12
2020
Cassione et al., Annals of the Rheumatic Diseases, doi:10.1136/annrheumdis-2020-217717 (Letter) COVID-19 infection in a northern-Italian cohort of systemic lupus erythematosus assessed by telemedicine
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..
May 11
2020
Shabrawishi et al., medRxix, doi:10.1101/2020.05.08.20095679 (Preprint) Negative nasopharyngeal SARS-CoV-2 PCR conversion in response to different therapeutic interventions
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 ..
May 11
2020
Rosenberg et al., JAMA, May 11, 2020, doi:10.1001/jama.2020.8630 Association of Treatment With Hydroxychloroquine or Azithromycin With In-Hospital Mortality in Patients With COVID-19 in New York State
35% higher mortality [p=0.31]. Restrospective 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 recei..
May 10
2020
Alberici et al., Kidney Int., 98:1, 20-26, July 1, 2020, doi:10.1016/j.kint.2020.04.030 (date from earlier preprint) 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
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 8
2020
Grassin-Delyle et al., Clinical Infectious Diseases, doi:10.1093/cid/ciaa546 (Ex Vivo) Chloroquine Inhibits the Release of Inflammatory Cytokines by Human Lung Explants
On human lung parenchymal explants, CQ concentration clinically achievable in the lung (100µM) inhibited the lipopolysaccharide-induced release of TNF-ɑ (by 76%), IL-6 (by 68%), CCL2 (by 72%), and CCL3 (by 67%). In addition to antiviral a..
May 8
2020
Carlucci et al., J. Med. Microbiol., Sep 15, 2020, doi: 10.1099/jmm.0.001250 (date from earlier preprint) Zinc sulfate in combination with a zinc ionophore may improve outcomes in hospitalized COVID-19 patients
Retrospective 932 patients showing that the addition of zinc to HCQ+AZ reduced mortality / transfer to hospice, ICU admission, and the need for ventilation.
May 7
2020
Konig et al., Annals of the Rheumatic Diseases, doi:10.1136/annrheumdis-2020-217690 (Letter) Baseline use of hydroxychloroquine in systemic lupus erythematosus does not preclude SARS-CoV-2 infection and severe COVID-19
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 use..
May 7
2020
Derendorf, H., Int. J. Antimicrobial Agents, 7 May 2020, doi:10.1016/j.ijantimicag.2020.106007 (Theory) Excessive lysosomal ion-trapping of hydroxychloroquine and azithromycin
Discusses pharmacokinetic properties of HCQ+AZ as a potential underlying mechanism of the observed antiviral effects.
May 7
2020
Geleris et al., NEJM, May 7, 2020, doi:10.1056/NEJMoa2012410 Observational Study of Hydroxychloroquine in Hospitalized Patients with Covid-19
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 1..
May 7
2020
Sermo (News) Sermo reports: COVID-19 treatment trends over 6 weeks and 33,700 interviews: Usage, efficacy and safety perceptions of most-used therapies
HCQ used by 55% of physicians worldwide for COVID. Survey of 6,150 physicians.
May 6
2020
Maisonnasse et al., Nature, 2020, doi:10.1038/s41586-020-2558-4 (date from earlier preprint) Hydroxychloroquine use against SARS-CoV-2 infection in non-human primates
Monkey study which reports no effect of HCQ or HCQ+AZ. However, there are several signs of effectiveness despite the very small sample sizes and 100% recovery of all treated and control monkeys. 58% reduction in lung lesions: the final da..
May 5
2020
Membrillo de Novales et al., Preprints 2020, 2020050057, doi:10.20944/preprints202005.0057.v1 (Preprint) Early Hydroxychloroquine Is Associated with an Increase of Survival in COVID-19 Patients: An Observational 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 5
2020
Million et al., Travel Med Infect Dis., 2020 May 5, doi:10.1016/j.tmaid.2020.101738 Early Treatment of COVID-19 Patients With Hydroxychloroquine and Azithromycin: A Retrospective Analysis of 1061 Cases in Marseille, France
Retrospective 1061 patients. HCQ+AZ safe and results in a low fatality rate.
May 5
2020
Gendelman et al., Autoimmunity Reviews, 19:7, July 2020, doi:10.1016/j.autrev.2020.102566 Continuous Hydroxychloroquine or Colchicine Therapy Does Not Prevent Infection With SARS-CoV-2: Insights From a Large Healthcare Database Analysis
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 res..
May 5
2020
Mitchell et al., SSRN, doi:10.2139/ssrn.3586954 (Preprint) Markedly Lower Rates of Coronavirus Infection and Fatality in Malaria-Endemic Regions – A Clue As to Treatment?
99% lower mortality [p=0.0001]. Analysis of COVID-19 amongst 2.4B people shows a wide counterintuitive disparity between well-developed and less-developed countries, with more affluent countries about one hundred times more likely to be infected and die due to COVID-19...
May 2
2020
Mallat et al., Medicine (Baltimore), doi:10.1097/MD.0000000000023720 (date from earlier preprint) Hydroxychloroquine is associated with slower viral clearance in clinical COVID-19 patients with mild to moderate disease: A retrospective 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..
May 1
2020
Mercuro et al., JAMA Cardiol., May 1, 2020, doi:10.1001/jamacardio.2020.1834 Risk of QT Interval Prolongation Associated With Use of Hydroxychloroquine With or Without Concomitant Azithromycin Among Hospitalized Patients Testing Positive for Coronavirus Disease 2019 (COVID-19)
Study of 90 hospitalized patients given HCQ, 53 also receiving AZ, 53% hypertension, 29% diabetes mellitus, baseline median QTc 473ms for HCQ, and 442ms for HCQ+AZ. Median change for HCQ+AZ ΔQTc of 23ms vs. 5.5ms for HCQ. Other factors su..
May 1
2020
Bessière et al., JAMA Cardiol., May 1, 2020, doi:10.1001/jamacardio.2020.1787 Assessment of QT Intervals in a Case Series of Patients With Coronavirus Disease 2019 (COVID-19) Infection Treated With Hydroxychloroquine Alone or in Combination With Azithromycin in an Intensive Care Unit
Study of 40 very serious condition ICU patients, 75% required invasive mechanical ventilation, 63% received vasoactive drugs, 50% received other treatments favoring QT prolongation. HCQ with or w/o AZ was given to 45% and 55% respectively..
May 2
2020
Seydi (News) Coronavirus: a study in Senegal confirms the effectiveness of hydroxychloroquine
Preliminary results of Senegal trial with 181 patients showing faster recovery with HCQ, and even faster recovery with HCQ+AZ.
Apr 30
2020
Meo et al., Eur. Rev. Med. Pharmacol. Sci. 2020, 24 (8), 4539-4547, doi:10.26355/eurrev_202004_21038 Efficacy of chloroquine and hydroxychloroquine in the treatment of COVID-19
Analysis of COVID-19 and malaria, finding that COVID-19 is highly pandemic in countries where malaria is least pandemic, and vice versa, suggesting that CQ/HCQ (widely used for malaria) are protective for COVID-19. This paper also include..
Apr 27
2020
Sánchez-Álvarez et al., Nefrología, doi:10.1016/j.nefroe.2020.04.002 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)
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 resul..
Apr 29
2020
Saleh et al., Circulation: Arrhythmia and Electrophysiology, doi:10.1161/CIRCEP.120.008662 The Effect of Chloroquine, Hydroxychloroquine and Azithromycin on the Corrected QT Interval in Patients with SARS-CoV-2 Infection
201 hospitalized patients. No serious side effects of HCQ. No instances of Torsade de pointes, or arrhythmogenic death were reported. They report that although use of these medications resulted in QT prolongation, clinicians seldom need t..
Apr 27
2020
Klimke et al., Med. Hypotheses, doi:10.1016/j.mehy.2020.109783 Hydroxychloroquine as an aerosol might markedly reduce and even prevent severe clinical symptoms after SARS-CoV-2 infection
Proposal to use HCQ as an aerosol in order to reach sufficient therapeutic levels at the alveolar epithelial cells. Authors suggest this will reduce adverse drug reactions compared with oral application, and the increase in tolerability e..
Apr 26
2020
Auld et al., Critical Care Medicine, doi:10.1097/ccm.0000000000004457 ICU and ventilator mortality among critically ill adults with COVID-19
3% higher mortality [p=1]. Retrospective 217 critically ill patients, 114 receiving HCQ, showing no significant difference in mortality.
Apr 25
2020
Andreani et al., Microbial Pathogenesis, doi:/10.1016/j.micpath.2020.104228 (In Vitro) In vitro testing of combined hydroxychloroquine and azithromycin on SARS-CoV-2 shows synergistic effect
In Vitro study showing that HCQ and AZ have a synergistic effect on SARS-CoV-2 at concentrations compatible with that obtained in human lung.
Apr 24
2020
Ashraf et al., medRxiv doi:10.1101/2020.04.20.20072421.t (Preprint) COVID-19 in Iran, a comprehensive investigation from exposure to treatment outcomes
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 21
2020
Izoulet M., SSRN, doi:10.2139/ssrn.3575899 (Preprint) Countries which Primarily Use Antimalarial Drugs As COVID-19 Treatment See Slower Dynamic of Daily Deaths
85% lower mortality [p=0.001]. Compares the dynamics of daily deaths in the 10 days following the 3rd death in countries using and not using [H]CQ, showing dramatically lower death in [H]CQ countries. This paper does not attempt to account for population age and other ..
Apr 21
2020
Magagnoli et al., Med (2020), doi:10.1016/j.medj.2020.06.001 (date from earlier preprint) Outcomes of hydroxychloroquine usage in United States veterans hospitalized with Covid-19
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 ..
Apr 17
2020
Lee at al., Int. J. Antimicrob. Agents, 2020, Apr 17, doi:10.1016/j.ijantimicag.2020.105988 Can Post-Exposure Prophylaxis for COVID-19 Be Considered as an Outbreak Response Strategy in Long-Term Care Hospitals?
Post exposure prophylaxis of 211 high-risk people after major exposure event in a long term care hospital, showing no positive cases after 14 days.
Apr 16
2020
Borba et al., JAMA Network Open, doi:10.1001/jamanetworkopen.2020.8857 Chloroquine diphosphate in two different dosages as adjunctive therapy of hospitalized patients with severe respiratory syndrome in the context of coronavirus (SARS-CoV-2) infection: Preliminary safety results of a randomized, double-blinded, phase IIb clinical trial (CloroCovid-19 Study)
Comparison of typical CQ dosage with high dosage CQ (600mg CQ twice daily for 10 days), showing higher mortality with high dosage, OR 2.8 [0.9 - 8.5] when controlled by age in multivariate analysis. Increased incidence of prolonged QT and..
Apr 15
2020
Esper et al., Prevent Senior Institute, São Paulo, Brazil (Preprint) Empirical treatment with hydroxychloroquine and azithromycin for suspected cases of COVID-19 followed-up by telemedicine
64% lower hospitalization [p=0.02]. 636 patients. HCQ+AZ reduced hospitalization 79% when used within 7 days (65% overall). Non-randomized.
Apr 15
2020
Brufsky, A., J. Medical Virology, doi:10.1002/jmv.25887 (Theory) Hyperglycemia, hydroxychloroquine, and the COVID‐19 pandemic
Theory on the effectiveness of HCQ. HCQ has been shown to block the polarization of macrophages to an M1 inflammatory subtype and is predicted to interfere with glycosylation of a number of proteins involved in the humoral immune response..
Apr 14
2020
Tang et al., BMJ 2020, 369, doi:10.1136/bmj.m1849 Hydroxychloroquine in patients with mainly mild to moderate coronavirus disease 2019: open label, randomised controlled trial
21% improved viral clearance [p=0.51]. 150 patients very late stage RCT showing no significant difference. Treatment very late, average 16.6 days after symptom onset. Data favorable to HCQ was deleted in the second version, see analysis [mediterranee-infection.com]. "[HC..
Apr 13
2020
Gao et al., Biosci Trends, May 21, 2020, 14:2, 156-158, doi:10.5582/bst.2020.03072, Epub Apr 13, 2020 (Review) Update on Use of Chloroquine/Hydroxychloroquine to Treat Coronavirus Disease 2019 (COVID-19)
Increasing evidence from completed clinical studies shows CQ and HCQ effective (HCQ more effective).
Apr 12
2020
Barbosa et al., Preprint (Preprint) Clinical outcomes of hydroxychloroquine in hospitalized patients with COVID-19: a quasi-randomized comparative 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 11
2020
Gautret et al., Travel Medicine and Infectious Disease, doi:10.1016/j.tmaid.2020.101663 Clinical and microbiological effect of a combination of hydroxychloroquine and azithromycin in 80 COVID-19 patients with at least a six-day follow up: A pilot observational study
Pilot study suggesting improvement with HCQ+AZ and recommending further study. 80 patients with relatively mild cases, no control group, and no attempt to analyze confounding factors.
Apr 10
2020
Lover, medRxiv, doi:10.1101/2020.03.22.20040949 (Preprint) (meta analysis) Quantifying treatment effects of hydroxychloroquine and azithromycin for COVID-19: a secondary analysis of an open label non-randomized clinical trial (Gautret et al, 2020)
Secondary analysis of Gautret et al. showing "modest to no impact of HCQ treatment, with more significant effects from [HCQ+AZ]".
Apr 3
2020
Fantini et al., Int J Antimicrob Agents, 55:5, doi:10.1016/j.ijantimicag.2020.105960 (Theory) Structural and molecular modelling studies reveal a new mechanism of action of chloroquine and hydroxychloroquine against SARS-CoV-2 infection
In Silico analysis confirming the antiviral properties of CQ, showing a new mechanism of action of CQ, and showing that HCQ is more potent than CQ.
Apr 1
2020
Huang et al., Journal of Molecular Cell Biology, Volume 12, Issue 4, April 2020, 322–325, doi:10.1093/jmcb/mjaa014 Treating COVID-19 with Chloroquine
92% improved recovery [p=0.02] and 83% lower pneumonia [p=0.22]. 22 patients. All CQ patients discharged by day 14 versus 50% of lopinavir/ritonavir patients. Symptom onset was very different - 2.5 days for CQ vs. 6.5 days for lopinavir/ritonavir.
Mar 31
2020
Chen et al., medRxiv doi:10.1101/2020.03.22.20040758 (Preprint) Efficacy of hydroxychloroquine in patients with COVID-19: results of a randomized clinical trial
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..
Mar 31
2020
Clementi et al., Front. Microbiol., 10 July 2020, doi:10.3389/fmicb.2020.01704 (date from earlier preprint) (In Vitro) Combined Prophylactic and Therapeutic Use Maximizes Hydroxychloroquine Anti-SARS-CoV-2 Effects in vitro
In Vitro study showing greater inhibition for combined pre and post-exposure treatment for Vero E6 and Caco-2 cells.
Mar 28
2020
Molina et al., Médecine et Maladies Infectieuses, 50:4, June 2020, 10.1016/j.medmal.2020.03.006 (date from earlier preprint) (Letter) No evidence of rapid antiviral clearance or clinical benefit with the combination of hydroxychloroquine and azithromycin in patients with severe COVID-19 infection
Report on 11 patients treated with HCQ with no control group. Authors suggest there is no evidence of benefit for HCQ based on PCR+ results for 8/10 patients at day 5-6. Binary PCR evaluation with an unknown Ct. Binary PCR does not distin..
Mar 26
2020
Zhong Nanshan (钟南山) (Preprint) Efficacy and safety of chloroquine for treatment of COVID-19. An open-label, multi-center, non-randomized trial
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 24
2020
Pagliano et al., Clin. Infect. Dis., 2020 Mar 24, doi:10.1093/cid/ciaa320 (Theory) Is Hydroxychloroquine a Possible Post-Exposure Prophylaxis Drug to Limit the Transmission to Health Care Workers Exposed to COVID19?
CQ and HCQ inhibit replication at early stages of infection, no similar effect reported for other drugs which are only able to interfere after cell infection. Large volume of existing data on safety. (8/23: we corrected the classification..
Mar 23
2020
Hu et al., Nature Nanotechnology, 15, 247–249, 2020, doi:10.1038/s41565-020-0674-9 (Theory) Insights from nanomedicine into chloroquine efficacy against COVID-19
CQ is known in nanomedicine research for the investigation of nanoparticle uptake in cells, and may have potential for the treatment of COVID-19.
Mar 21
2020
ICMR, Indian Council of Medical Research (Advisory) Advisory on the use of hydroxy-chloroquine as prophylaxis for SARS-CoV-2 infection
Recommends HCQ for prophylaxis in asymptomatic healthcare workers as found effective in-vitro and in-vivo.
Mar 20
2020
Hu et al., Shanghai Combined Task Force on COVID-19 (News) Shanghai Experience of COVID-19 Management
Clinical studies of HCQ with 184 cases and 21 hospitals show HCQ is effective.
Mar 18
2020
Liu et al., Cell Discovery 6, 16 (2020), doi:10.1038/s41421-020-0156-0 (In Vitro) Hydroxychloroquine, a less toxic derivative of chloroquine, is effective in inhibiting SARS-CoV-2 infection in vitro
In Vitro study showing that HCQ is effective in vitro and less toxic than CQ. In addition to direct antiviral activity, HCQ is a safe and successful anti-inflammatory agent that has been used extensively in autoimmune diseases and can sig..
Mar 17
2020
Gautret et al., Int. J. of Antimicrobial Agents, doi:10.1016/j.ijantimicag.2020.105949 (date from earlier preprint) Hydroxychloroquine and azithromycin as a treatment of COVID-19: results of an open-label non-randomized clinical trial
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]. De..
Mar 17
2020
Sahraei et al., Int. J. Antimicrobial Agents, April 2020, 55:4, doi:10.1016/j.ijantimicag.2020.105945 (Review) Aminoquinolines against coronavirus disease 2019 (COVID-19): chloroquine or hydroxychloroquine
Discussion of mechanisms of action, CQ vs. HCQ, early studies, safety.
Mar 13
2020
Todaro and Rigano (Review) (Preprint) An Effective Treatment for Coronavirus (COVID-19)
Discussion of existing research, treatment guidelines, and mechanisms of action for CQ and HCQ, recommending use.
Mar 12
2020
Devaux et al., International Journal of Antimicrobial Agents, doi:10.1016/j.ijantimicag.2020.105938 (Theory) New insights on the antiviral effects of chloroquine against coronavirus: what to expect for COVID-19?
Discusses mechanisms of CQ interference with the SARS-CoV-2 replication cycle.
Mar 10
2020
Cortegiani et al., J. Crit. Care, June 2020, 57:279-283, doi:10.1016/j.jcrc.2020.03.005, Epub Mar 10, 2020 (meta analysis) A Systematic Review on the Efficacy and Safety of Chloroquine for the Treatment of COVID-19
Review of six articles and 23 ongoing clinical trials in China recommending research and clinical use adhering to MEURI.
Mar 9
2020
Yao et al., Clin. Infect. Dis., 2020 Mar 9, doi:10.1093/cid/ciaa237 (In Vitro) In Vitro Antiviral Activity and Projection of Optimized Dosing Design of Hydroxychloroquine for the Treatment of Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2)
In Vitro study showing that HCQ is more potent than CQ in vitro for inhibiting SARS-CoV-2. Simulates HCQ concentration in lung fluid and provides dosing recommendations. See also [academic.oup.com, sciencedirect.com].
Mar 6
2020
Chen et al., J. Zhejiang University (Med Sci), doi:10.3785/j.issn.1008-9292.2020.03.03 A pilot study of hydroxychloroquine in treatment of patients with common coronavirus disease-19 (COVID-19)
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 a..
Mar 4
2020
Colson et al., Int J. Antimicrob Agents, doi: 10.1016/j.ijantimicag.2020.105932. Epub 2020 Mar 4. (Review) Chloroquine and Hydroxychloroquine as Available Weapons to Fight COVID-19
Recommending CQ and HCQ for COVID-19 based on 20 clinical studies in China and a strong rationale for use.
Feb 20
2020
Jiang et al., Chin. J. Tuberc. Respir. Dis., 2020, 43, doi:10.3760/cma.j.issn.1001-0939.2020.0019 Expert Consensus on Chloroquine Phosphate for the Treatment of Novel Coronavirus Pneumonia
Early trials in China show CQ results in shorter hospital stays and improved patient outcomes.
Feb 19
2020
Gao et al., BioScience Trends, 2020, doi:10.5582/bst.2020.01047 Breakthrough: Chloroquine phosphate has shown apparent efficacy in treatment of COVID-19 associated pneumonia in clinical studies
Results from 15 clinical trials in China showing CQ is effective.
Feb 17
2020
Sun, Y., deputy head of the China National Center for Biotechnology Development (News) Antimalarial drug confirmed effective on COVID-19
HCQ under clinical trials in >10 hospitals in China and has shown fairly good efficacy.
Feb 11
2020
Xia et al., ChiCTR2000029741 (Preprint) Efficacy of Chloroquine and Lopinavir/ Ritonavir in mild/general novel coronavirus (CoVID-19) infections: a prospective, open-label, multicenter randomized controlled clinical 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 co..
Feb 4
2020
Wang et al., Cell Res. 30, 269–271, doi:L10.1038/s41422-020-0282-0 (In Vitro) Remdesivir and chloroquine effectively inhibit the recently emerged novel coronavirus (2019-nCoV) in vitro
In Vitro study showing that Remdesivir and CQ potently blocked SARS-CoV-2 infection.
2017
Chhonker et al., Journal of Chromatography B, Analytical Technologies in the Biomedical and Life Sciences, 22 Nov 2017, 1072:320-327 doi:10.1016/j.jchromb.2017.11.026 Simultaneous quantitation of hydroxychloroquine and its metabolites in mouse blood and tissues using LC-ESI-MS/MS: An application for pharmacokinetic studies
Presents a method for quantification of HCQ in mouse blood and tissues. They show a lung concentration significantly higher than other organs, and about 30 times the blood concentration.
2014
Browning, D., Pharmacology of Chloroquine and Hydroxychloroquine, 2014, 35-63, doi:10.1007/978-1-4939-0597-3_2 Pharmacology of Chloroquine and Hydroxychloroquine
Review of the pharmacology of CQ and HCQ. Some notable points: - HCQ and CQ are equipotent but CQ is more toxic, the therapeutic ratio is higher for HCQ. - Concentrations in different tissues can vary >10x, in particular the concentration..
2014
de Wilde et al., Antimicrobial Agents and Chemotherapy, Jul 2014, 58:8, 4875-4884, doi:10.1128/AAC.03011-14 (In Vitro) Screening of an FDA-Approved Compound Library Identifies Four Small-Molecule Inhibitors of Middle East Respiratory Syndrome Coronavirus Replication in Cell Culture
CQ inhibits SARS-CoV, MERS-CoV, and HCoV-229E-GFP replication in the low-micromolar range.
2012
Yan et al., Cell Research, 23, 300–302, doi:10.1038/cr.2012.165 Anti-malaria drug chloroquine is highly effective in treating avian influenza A H5N1 virus infection in an animal model
CQ, a known autophagy inhibitor that is in clinical use, can efficiently ameliorate acute lung injury and dramatically improve the survival rate in mice infected with live avian influenza A H5N1 virus.
2009
Keyaerts et al., Antimicrob. Agents Chemother, August 2009, 53(8), doi:0.1128/AAC.01509-08 Antiviral Activity of Chloroquine against Human Coronavirus OC43 Infection in Newborn Mice
CQ inhibits HCoV-OC43 replication in HRT-18 cells. A lethal HCoV-OC43 infection in newborn C57BL/6 mice can be treated with CQ acquired transplacentally or via maternal milk. The highest survival rate (98.6%) was found when mother mice we..
2008
Kono et al., Antiviral Research, 77:2, February 2008, 150-152, 10.1016/j.antiviral.2007.10.011 (In Vitro) Inhibition of human coronavirus 229E infection in human epithelial lung cells (L132) by chloroquine: Involvement of p38 MAPK and ERK
CQ significantly decreased viral replication of HCoV-229E at concentrations lower than in clinical usage. CQ affects the activation of p38 mitogen-activated protein kinase (MAPK) and extracellular signal-regulated kinase (ERK). p38 MAPK i..
2006
Savarino et al., Lancet Infect. Dis., doi:10.1016/S1473-3099(06)70361-9 (In Vitro) New insights into the antiviral effects of chloroquine
Update to 2003 paper, not included in the study count or percentages. Hypothesis of CQ inhibiting SARS replication has been confirmed in two in-vitro studies. CQ affected an early stage of SARS replication.
2005
Vincent et al., Virol. J. 2:69, 2005, doi:10.1186/1743-422X-2-69 (In Vitro) Chloroquine is a potent inhibitor of SARS coronavirus infection and spread
In Vitro study, SARS-CoV-1, not included in the study count or percentages. CQ has strong antiviral effects on SARS CoV infection when cells treated either before or after exposure, suggesting prophylactic and treatment use. Describes thr..
2004
Keyaerts et al., Biochem. Biophys. Res. Comm., 323:1, 8 October 2004, doi:10.1016/j.bbrc.2004.08.085 (In Vitro) In vitro inhibition of severe acute respiratory syndrome coronavirus by chloroquine
In Vitro study, SARS-CoV-1, not included in the study count or percentages. IC50 of CQ for antiviral activity (8.8) is significantly lower than cytostatic activity CC50 (261.3), selectivity index of 30. IC50 for inhibition of SARS-CoV in ..
2003
Savarino et al., Lancet Infect. Dis., doi:10.1016/S1473-3099(03)00806-5 (Theory) Effects of chloroquine on viral infections: an old drug against today's diseases
Not included in the study count or percentages. Discussion/review noting that CQ exerts antiviral effects, inhibiting the replication of several viruses including members of the flaviviruses, retroviruses, and coronaviruses. Notes that CQ..
1918
Burrows, E., Medical Record, 97:6, 235, Feb 7, 1920 A confirmatory report upon the abortive action of quinine dihydrochloride
Quinine was found to be effective for the Spanish Flu in 1918.
1901
Yeo, B., 1901 A manual of medical treatment or clinical therapeutics
Quinine is refered to as "the remedy that is most deserving of confidence in the treatment of influenza".
1894
Mossé, Lancet, Nov 3, 1894 Pathogenesis and Treatment of Influenza
Lancet study showing quinine protected rabbits from influenza and recommending use for prophylaxis and treatment.
1890
Le Grelot (News) Quinine use for the Russian influenze pandemic if 1889-1890
Quinine and antipyrine, a bitherapy for defying death during the Russian influenza pandemic of 1889-1890 (around 40,000 deaths in France at the beginning of 1890).
1889
Edwin Wiley Grove (News) Laxative Bromo Quinine
Quinine was considered effective for respiratory infections as early as 1889.
For search methods, inclusion criteria, effect extraction criteria (more serious outcomes have priority), PRISMA answers, and statistical methods see methods. Meta, Theory, Safety, Review, News, and Retracted items are not included in the study count. There is a total of 537 items. Studies with preprints and journal versions are listed under the earlier preprint date.
Please send us corrections, updates, or comments. Vaccines and treatments are complementary. All practical, effective, and safe means should be used based on risk/benefit analysis. No treatment, vaccine, or intervention is 100% available and effective for all current and future variants. We do not provide medical advice. Before taking any medication, consult a qualified physician who can provide personalized advice and details of risks and benefits based on your medical history and situation. FLCCC and WCH provide treatment protocols.
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