Clin Transl Sci. 2021 Feb 19. doi: 10.1111/cts.13001. Online ahead of print.
Many meta-analyses have been published about the efficacy of Hydroxychloroquine (HCQ) in COVID-19. Most of them included observational studies, and few have assessed HCQ as a prophylaxis or evaluated its safety profile. We searched multiple databases and preprint servers for randomized controlled trials (RCTs) that assessed HCQ for the treatment or prevention of COVID-19. We summarized the effect of HCQ on mortality, viral clearance, and other clinical outcomes. Out of 768 papers screened, 21 RCTs with a total of 14,138 patients were included. A total of 9 inpatient and 3 outpatient RCTs assessed mortality in 8,596 patients with a pooled risk difference of 0.01 [95% CI 0.00, 0.03, I2= 1%, P=0.07]. Six studies assessed viral clearance at 7 days with a pooled risk ratio (RR) of 1.11 [95% CI 0.86, 1.42, I2= 61%, P=0.44] and 5 studies at 14 days with a pooled RR of 0.96 [95% CI 0.89, 1.04, I2= 0%, P=0.34]. Several trials showed no significant effect of HCQ on other clinical outcomes and. Five prevention RCTs with 5012 patients found no effect of HCQ on the risk of acquiring COVID-19. Thirteen trials showed that HCQ was associated with increased risk of adverse events. We observed, with high level of certainty of evidence, that HCQ is not effective in reducing mortality in COVID-19 patients. Lower certainty evidence also suggests that HCQ neither improves viral clearance and other clinical outcomes, nor prevents COVID-19 infection in patients with high-risk exposure. HCQ is associated with an increased rate of adverse events.