Brief communication: A meta-analysis of randomized trials of hydroxychloroquine for the prevention of COVID-19

Garcia-Albeniz, X.; Del Amo, J.; Polo, R.; Morales Asencio, J. M.; Hernan, M. A.

Background: There is disagreement about whether hydroxychloroquine (HCQ) is effective as prophylaxis for COVID-19. We conducted a meta-analysis of randomized trials that study the effectiveness of HCQ to prevent COVID-19. Methods and Findings: A search of PubMed, Embase, medRxiv, and clinicaltrials.gov found three completed randomized trials: one pre-exposure prophylaxis trial and two post-exposure prophylaxis trials. We obtained or calculated the risk ratio of COVID-19 diagnosis for assignment to HCQ versus no HCQ (either placebo or usual care) for each trial, and then pooled the risk ratio estimates. The risk ratio estimated for each of the individual trials were 0.74 (95% CI 0.50-1.10), 0.83 (95% CI: 0.58-1.18), and 0.69 (95% CI: 0.35-1.37). The pooled risk ratio estimate was 0.78 (95% CI: 0.61-0.99). All three trials found a similar rate of adverse effects in the HCQ and no HCQ groups. Discussion: The available evidence indicates that HCQ reduces the risk of COVID-19 by about 20%. Yet the findings from the randomized trials were widely interpreted as evidence of lack of effectiveness of HCQ, simply because they were not statistically significant when taking them individually. Completion of the ongoing prophylaxis trials is needed to generate more precise estimates of the effectiveness of HCQ to prevent COVID-19.