The Efficacy and Safety of Hydroxychloroquine for COVID-19 Prophylaxis: Systematic Review and Meta-analysis (Preprint)

BACKGROUND The efficacy and safety of hydroxychloroquine (HCQ) for COVID-19 prophylaxis remains highly controversial. OBJECTIVE This study aimed to evaluate the efficacy and safety of HCQ to prevent COVID-19. METHODS Electronic searches were conducted up to December 21, 2022 in Pubmed/MEDLINE, Embase, medRxiv, the Cochrane COVID-19 Register of Controlled Trials, clinicaltrials.gov, and the WHO International Clinical Trials Registry Platform. The primary outcomes included COVID-19 transmission, and mortality. Treatment effects were reported as relative risk (RR) for dichotomous variables with 95% confidence intervals (CI). We performed either a fixed- or random-effects model to pool the results of individual studies depending on the presence of heterogeneity. RESULTS Fifteen randomized trials were included: 10 pre-exposure prophylaxis trials and 5 post-exposure prophylaxis trials. The pooled RR of COVID-19 transmission in the pre-exposure prophylaxis trials was 0.73 (95% CI 0.66-0.81) when using either a fixed-effect model. The pooled RR of COVID-19 transmission in the post-exposure prophylaxis trials was 0.93 (95% CI 0.76-1.15). The final pooled RR, including all pre- and post-exposure trials, was 0.78 (95% CI 0.74-0.86). CONCLUSIONS Available evidence suggested that prophylactic HCQ for people at risk of exposure to SARS-CoV-2 was safe and effective. Therefore, HCQ as prophylaxis (especially as pre-exposure prophylaxis) for COVID-19 is recommended. CLINICALTRIAL PROSPERO (Prospective International Register of Systematic Reviews) CRD42022357880; https://www.crd.york.ac.uk/prospero/display_record.php?RecordID=257299