Treatment Response to Hydroxychloroquine and Antibiotics for mild to moderate COVID-19: a retrospective cohort study from South Korea

An et al., medRxiv, doi:10.1101/2020.07.04.20146548, Jul 2020

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HCQ for COVID-19

1st treatment shown to reduce risk in March 2020, now with p < 0.00000000001 from 423 studies, used in 59 countries.

Lower risk for mortality, hospitalization, progression, recovery, cases, and viral clearance.

No treatment is 100% effective. Protocols combine treatments.

5,500+ studies for 121 treatments. c19hcq.org

Retrospective of hospitalized patients with 31 HCQ patients and 195 standard treatment patients, not showing a significant difference in terms of viral clearance or recovery. There was no mortality in either group.

"It is notable that HQ plus antibiotics group had worse baseline clinical profiles (i.e. higher percentage of moderate severity patients, more patients with fever >=37.5C, higher average body temperature) and prognostic indicators such as age, LDH, lymphocyte count, and CRP".

We note that propensity score matching removed almost all of the male patients in the control group (40% -> 5%) but increased the percentage of male patients in the treatment group. This provides a large advantage to the control group because there is a very large difference in severity and mortality based on gender1.

In terms of viral RNA clearance we note that other research has found that "active viral replication drops quickly after the first week, and viable virus was not found after the second week of illness despite the persistence of PCR detection of RNA”2.

Viral load measured by PCR may not accurately reflect infectious virus measured by viral culture. Porter et al. show that viral load early in infection was correlated with infectious virus, but viral load late in infection could be high even with low or undetectable infectious virus. Assessing viral load later in infection may underestimate reductions in infectious virus with treatment.

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time to viral clearance, 3.0% lower, HR 0.97, p = 0.92, treatment 31, control 195.

Effect extraction follows pre-specified rules prioritizing more serious outcomes. Submit updates

1. ncbi.nlm.nih.gov, www.ncbi.nlm.nih.gov/pmc/articles/PMC7247289/.www.ncbi.nlm.nih.gov/pmc/articles/PMC7247289/.

2. ams.edu.sg, www.ams.edu.sg/view-pdf.aspx?file=media%5c5556_fi_331.pdf&ofile=Period+of+Infectivity+Position+Statement+(final)+23-5-20+(logos).pdf.www.ams.edu.sg/view-pdf.aspx?file=media%5c5556_fi_331.pdf&ofile=Period+of+Infectivity+Position+Statement+(final)+23-5-20+(logos).pdf.

3. Porter et al., The ratio between SARS-CoV-2 RNA viral load and culturable viral titer differs depending on stage of infection, medRxiv, doi:10.1101/2023.07.06.23292300.medrxiv.org, doi.org.

An et al., 7 Jul 2020, retrospective, South Korea, preprint, 12 authors.

This Paper HCQ All

Treatment Response to Hydroxychloroquine and Antibiotics for mild to moderate COVID-19: a retrospective cohort study from South Korea

Min Ho An, MD Min Seo Kim, MD Yu-Kyung Park, MD, PhD Bong-Ok Kim, MD Seok Ho Kang, PhD Won Jun Kim, MD Sung Kyu Park, MD, PhD Hea-Woon Park, MD Wonjong Yang, MD Joonyoung Jang, MD, KMD Soon-Woo Jang, DSS, PhD Tae-Ho Hwang

doi:10.1101/2020.07.04.20146548

Objectives: To assess the efficacy of hydroxychloroquine on mild-moderate COVID-19 patients in South Korea. Methods: A retrospective cohort study of the 358 laboratory-confirmed SARS-CoV-2 (COVID-19) patients was conducted. 226 patients met inclusion criteria for analysis. Propensity score matching (PSM) and Cox regression method were utilized to control and adjust for confounding factors. Mild to moderate COVID-19 patients were managed with hydroxychloroquine (HQ) plus antibiotics (n = 31) or conservative treatment (n = 195). Results: Kaplan-Meier curves drawn using propensity score-matched data revealed no differences between the length of time to viral clearance and duration of hospital stay between the two treatment arms (p=0.18, p=0.088). Multivariable Cox regression analysis similarly showed that time to viral clearance(Hazard ratio (HR) 0.97, [95%-confidence interval (CI): 0.57-1.67]) and symptom duration(HR 1.05, [95%-CI: 0.62-1.78]) were not different between groups. No severe adverse event or death was observed in either group. Conclusions: HQ with antibiotics was not associated with better clinical outcomes in terms of time to viral clearance, length of hospital stay, and duration of symptoms compared to conservative treatment alone. Large prospective randomized trials are necessary for definitive conclusions.

References

Boulware, Pullen, Bangdiwala, Pastick, Lofgren et al., A Randomized Trial of Hydroxychloroquine as Postexposure Prophylaxis for Covid-19, The New England journal of medicine

Campbell, Marrie, Anstey, Dickinson, Ackroyd-Stolarz, The contribution of blood cultures to the clinical management of adult patients admitted to the hospital with community-acquired pneumonia: a prospective observational study, Chest

Chen, Hu, Zhang, Jiang, Han et al., Efficacy of hydroxychloroquine in patients with COVID-19: results of a randomized clinical trial, medRxiv

Fantini, Chahinian, Yahi, Synergistic antiviral effect of hydroxychloroquine and azithromycin in combination against SARS-CoV-2: What molecular dynamics studies of virus-host interactions reveal, Int J Antimicrob Agents, doi:10.1016/j.ijantimicag.2020.106020

Galvis, Spinelli, Tello, Sossa, Higuera et al., Hydroxychloroquine as Prophylaxis for Coronavirus SARS-CoV-2 Infection: Review of the Ongoing Clinical Trials, Archivos de bronconeumologia

Gautret, Lagier, Parola, Hoang, Meddeb et al., Hydroxychloroquine and azithromycin as a treatment of COVID-19: results of an open-label non-randomized clinical trial, International Journal of Antimicrobial Agents, doi:10.1016/j.ijantimicag.2020.105949

Geleris, Sun, Platt, Zucker, Baldwin et al., Observational Study of Hydroxychloroquine in Hospitalized Patients with Covid-19, New England Journal of Medicine

Jefferson, Dalton, Escobar, Allison, Transportation delay and the microbiological quality of clinical specimens, Am J Clin Pathol

Kim, An, Kim, Hwang, Comparative efficacy and safety of pharmacological interventions for the treatment of COVID-19: A systematic review and network meta-analysis of confounder-adjusted 20212 hospitalized patients, medRxiv

Kim, Huh, Heo, Joo, Kim et al., Interim Guidelines on Antiviral Therapy for COVID-19, Infect Chemother

Kim, Sung, Kim, Kim, Clinical Relevance of Positive NOW™ Legionella Urinary Antigen Test in a Tertiary-Care Hospital in Korea, Korean J Lab Med

Liu, Cao, Xu, Wang, Zhang et al., Hydroxychloroquine, a less toxic derivative of chloroquine, is effective in inhibiting SARS-CoV-2 infection in vitro, Cell Discovery

Mahévas, Tran, Roumier, Chabrol, Paule et al., Clinical efficacy of hydroxychloroquine in patients with covid-19 pneumonia who require oxygen: observational comparative study using routine care data, BMJ

Mercuro, Yen, Shim, Maher, Mccoy et al., Risk of QT Interval Prolongation Associated With Use of Hydroxychloroquine With or Without Concomitant Azithromycin Among Hospitalized Patients Testing Positive for Coronavirus Disease, JAMA Cardiol

Pirracchio, Resche-Rigon, Chevret, Evaluation of the Propensity score methods for estimating marginal odds ratios in case of small sample size, BMC Medical Research Methodology

Rismanbaf, Potential Treatments for COVID-19; a Narrative Literature Review, Arch Acad Emerg Med

Rosenberg, Dufort, Udo, Wilberschied, Kumar et al., Association of Treatment With Hydroxychloroquine or Azithromycin With In-Hospital Mortality in Patients With COVID-19, JAMA

Roson, Fernandez-Sabe, Carratala, Verdaguer, Dorca et al., Contribution of a urinary antigen assay (Binax NOW) to the early diagnosis of pneumococcal pneumonia, Clin Infect Dis

Saleh, Gabriels, Chang, Kim, Mansoor et al., The Effect of Chloroquine, Hydroxychloroquine and Azithromycin on the Corrected QT Interval in Patients with SARS-CoV-2 Infection, Circulation: Arrhythmia and Electrophysiology, doi:10.1161/CIRCEP.120.008662

Tang, Cao, Han, Wang, Chen et al., Hydroxychloroquine in patients with mainly mild to moderate coronavirus disease 2019: open label, randomised controlled trial, BMJ

Van Der Eerden, Vlaspolder, De Graaff, Groot, Jansen et al., Value of intensive diagnostic microbiological investigation in low-and high-risk patients with community-acquired pneumonia, Eur J Clin Microbiol Infect Dis

Wang, Cao, Zhang, Yang, Liu et al., Remdesivir and chloroquine effectively inhibit the recently emerged novel coronavirus (2019-nCoV) in vitro, Cell Research

Wu, Mcgoogan, Characteristics of and important lessons from the coronavirus disease

Yao, Ye, Zhang, Cui, Huang et al., Vitro Antiviral Activity and Projection of Optimized Dosing Design of Hydroxychloroquine for the Treatment of Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2), Clinical Infectious Diseases

Yusuf, Sharma, Luqmani, Downes, Hydroxychloroquine retinopathy, Eye (Lond)

Zhao, Zhang, Li, Ma, Gu et al., Incidence, clinical characteristics and prognostic factor of patients with COVID-19: a systematic review and meta-analysis, medRxiv

DOI record: { "DOI": "10.1101/2020.07.04.20146548", "URL": "http://dx.doi.org/10.1101/2020.07.04.20146548", "abstract": "AbstractObjectivesTo assess the efficacy of hydroxychloroquine on mild-moderate COVID-19 patients in South Korea.MethodsA retrospective cohort study of the 358 laboratory-confirmed SARS-CoV-2 (COVID-19) patients was conducted. 226 patients met inclusion criteria for analysis. Propensity score matching (PSM) and Cox regression method were utilized to control and adjust for confounding factors. Mild to moderate COVID-19 patients were managed with hydroxychloroquine (HQ) plus antibiotics (n = 31) or conservative treatment (n = 195).ResultsKaplan-Meier curves drawn using propensity score-matched data revealed no differences between the length of time to viral clearance and duration of hospital stay between the two treatment arms (p=0.18, p=0.088). Multivariable Cox regression analysis similarly showed that time to viral clearance(Hazard ratio (HR) 0.97, [95%-confidence interval (CI): 0.57-1.67]) and symptom duration(HR 1.05, [95%-CI: 0.62-1.78]) were not different between groups. No severe adverse event or death was observed in either group.ConclusionsHQ with antibiotics was not associated with better clinical outcomes in terms of time to viral clearance, length of hospital stay, and duration of symptoms compared to conservative treatment alone. 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Late treatment
is less effective

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