Hydroxychloroquine use in hospitalised patients with COVID-19: An observational matched cohort study

Kalligeros et al., Journal of Global Antimicrobial Resistance, doi:10.1016/j.jgar.2020.07.018, Aug 2020
Mortality -67% improvement lower risk ← → higher risk HCQ for COVID-19  Kalligeros et al.  LATE TREATMENT Is late treatment with HCQ beneficial for COVID-19? Retrospective 108 patients in the USA Higher mortality with HCQ (not stat. sig., p=0.57) c19early.org Kalligeros et al., J. Global Antimicro.., Aug 2020 0 0.5 1 1.5 2+ RR
HCQ for COVID-19
1st treatment shown to reduce risk in March 2020, now with p < 0.00000000001 from 424 studies, used in 59 countries.
Lower risk for mortality, hospitalization, progression, recovery, cases, and viral clearance.
No treatment is 100% effective. Protocols combine treatments.
6,300+ studies for 210+ treatments. c19early.org
Meta Analysis
Small retrospective database analysis of 36 patients receiving HCQ not showing significant differences. Confounding by indication is likely.
Standard of Care (SOC) for COVID-19 in the study country, the USA, is very poor with very low average efficacy for approved treatments1. Only expensive, high-profit treatments were approved for early treatment. Low-cost treatments were excluded, reducing the probability of early treatment due to access and cost barriers, and eliminating complementary and synergistic benefits seen with many low-cost treatments.
Important missing comments or errors? Let us know.
risk of death, 67.0% higher, HR 1.67, p = 0.57, treatment 36, control 72.
Effect extraction follows pre-specified rules prioritizing more serious outcomes. Submit updates
Kalligeros et al., 5 Aug 2020, retrospective, USA, peer-reviewed, 13 authors, average treatment delay 6.0 days.
$0 $500 $1,000+ Efficacy vs. cost for COVID-19 treatment protocols c19early.org December 2025 USA Russia Sudan Angola Colombia Kenya Mozambique Vietnam Peru Philippines Spain Brazil Italy France Japan Canada China Uzbekistan Nepal Ethiopia Iran Ghana Mexico South Korea Germany Bangladesh Saudi Arabia Algeria Morocco Yemen Poland India DR Congo Madagascar Thailand Uganda Venezuela Nigeria Egypt Bolivia Taiwan Zambia Fiji Bosnia-Herzegovina Ukraine Côte d'Ivoire Bulgaria Greece Slovakia Singapore Iceland New Zealand Czechia Mongolia Israel Trinidad and Tobago Hong Kong North Macedonia Belarus Qatar Panama Serbia CAR USA favored high-profit treatments.The average efficacy of treatments was very low.High-cost protocols reduce early treatment, andforgo complementary/synergistic benefits. More effective More expensive 75% 50% 25% ≤0%
$0 $500 $1,000+ Efficacy vs. cost for COVID-19treatment protocols worldwide c19early.org December 2025 USA Russia Sudan Angola Colombia Kenya Mozambique Vietnam Peru Philippines Spain Brazil Italy France Japan Canada China Uzbekistan Nepal Ethiopia Iran Ghana Mexico South Korea Germany Bangladesh Saudi Arabia Algeria Morocco Yemen Poland India DR Congo Madagascar Thailand Uganda Venezuela Nigeria Egypt Bolivia Taiwan Zambia Fiji Ukraine Côte d'Ivoire Eritrea Bulgaria Greece Slovakia Singapore New Zealand Malawi Czechia Mongolia Israel Trinidad and Tobago North Macedonia Belarus Qatar Panama Serbia Syria USA favored high-profit treatments.The average efficacy was very low.High-cost protocols reduce early treatment,and forgo complementary/synergistic benefits. More effective More expensive 75% 50% 25% ≤0%
Hydroxychloroquine use in hospitalised patients with COVID-19: An observational matched cohort study
Markos Kalligeros, Fadi Shehadeh, Eleftheria Atalla, Evangelia K Mylona, Su Aung, Aakriti Pandita, Jerry Larkin, Martha Sanchez, Francine Touzard-Romo, Amy Brotherton, Rajeev Shah, Cheston B Cunha, Eleftherios Mylonakis
Journal of Global Antimicrobial Resistance, doi:10.1016/j.jgar.2020.07.018
To assess the efficacy and safety of hydroxychloroquine with or without azithromycin) in hospitalized adult patients with COVID-19. Methods: We utilized a hospital based prospective data registry. The primary end point was to assess the impact of hydroxychloroquine with or without azithromycin, on outcome, length of hospitalization, and time to clinical improvement. We utilized treatment effects with inverse-probability-weighting and Cox proportional hazards models. All analyses accounted for age, gender, race, severity on admission, days from symptoms onset and chronic comorbidities. Results: 36 patients received hydroxychloroquine and were age-and sex-matched to 72 patients with COVID-19 who received supportive care. Compared to supportive care, the use of HCQ did not shorten the time to clinical improvement (+0.23 days; 95% CI: À1.8-2.3 days) nor did it shorten the duration of hospital stay (+0.91 days; 95% CI: À1.1-2.9 days). Additionally, HCQ did not decrease the risk of COVID-19 in-hospital death (aHR 1.67; 95% CI: 0.29-9.36). Finally, we observed a slight QTc prolongation from a baseline of 444 AE 26 ms to 464 AE 32 ms (meanAESD) among patients receiving hydroxychloroquine with or without azithromycin. Conclusion: This study did not yield benefits from hydroxychloroquine use in patients with COVID-19 and monitoring for adverse events is warranted. Nevertheless, the treatment was safely studied under the guidance of an antimicrobial stewardship program.
Ethical approval This study received ethical approval from the Institutional Review Board (IRB) of the Rhode Island Hospital (Providence, RI, USA) [ref. #005120]. Appendix A. Supplementary data Supplementary material related to this article can be found, in the online version, at doi:https://doi.org/10.1016/j.jgar.2020.07.018.
References
Geleris, Sun, Platt, Zucker, Baldwin et al., Observational study of hydroxychloroquine in hospitalized patients with COVID-19, N Engl J Med, doi:10.1056/NEJMoa2012410
Magagnoli, Narendran, Pereira, Cummings, Hardin et al., Outcomes of hydroxychloroquine usage in United States veterans hospitalized with COVID-19, medRxiv, doi:10.1101/2020.04.16.20065920
Mahevas, Tran, Roumier, Chabrol, Paule et al., No evidence of clinical efficacy of hydroxychloroquine in patients hospitalized for COVID-19 infection with oxygen requirement: results of a study using routinely collected data to emulate a target trial, medRxiv, doi:10.1101/2020.04.10.20060699
Wang, Cao, Zhang, Yang, Liu et al., Remdesivir and chloroquine effectively inhibit the recently emerged novel coronavirus (2019-nCoV) in vitro, Cell Res, doi:10.1038/s41422-020-0282-0
Yao, Ye, Zhang, Cui, Huang et al., 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), Clin Infect Dis, doi:10.1093/cid/ciaa237
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Late treatment
is less effective
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