| Summary: | Background: Many studies have evaluated the use of hydroxychloroquine in COVID-19. Most retrospective observational studies demonstrate a benefit of using HCQ on mortality, but not most randomized clinical trials. Methods: We analyzed raw data collected from a cohort of 30,423 patients with COVID-19 cared for at IHU Méditerranée Infection in Marseille France and extracted from the DRYAD open data platform. We performed univariate and multivariable logistic regressions with all-cause mortality within six weeks. Multivariable logistic regressions were adjusted for sex, age group (<50, 50–69, 70–89 and > 89 years), periods (or variants), and type of patient management. Results: Among 30,202 patients for whom information on treatment was available, 191/23,172 (0.82%) patients treated with HCQ-AZ died, compared to 344/7030 (4.89%) who did not receive treatment with HCQ-AZ. HCQ-AZ therapy was associated with a lower mortality than treatment without HCQ-AZ (odds ratio (OR) 0.16; 95% confidence interval (CI), 0.14–0.19). After adjustment for sex, age, period, and patient management, HCQ-AZ was associated with a significantly lower mortality rate (adjusted OR (aOR) 0.55, 95% CI 0.45–0.68). On a subsample of 21,664 patients with available variant information, results remained robust after adjustment on sex, age, patient management and variant (aOR 0.55; 95% CI 0.44–0.69). On a subsample of 16,063 patients, HCQ-AZ was still associated with a significantly lower mortality rate (aOR 0.47, 95%CI 0.29–0.75) after adjustment for sex, age, period, patient management, vaccination status and comorbidities. Conclusion: Analysis of this large online database showed that HCQ-AZ was consistently associated with the lowest mortality.
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