In coronavirus disease-2019 (COVID-19) patients, prophylactic hydroxychloroquine was found to have no clinical benefit and displayed an elevated risk of adverse events in comparison with placebo or no prophylaxis.

A systematic review and meta-analysis were performed to explore the efficacy and safety of hydroxychloroquine as prophylaxis for COVID-19.

Databases like clinicaltrials.gov, EMBASE, the Cochrane COVID-19 Register of Controlled Trials, MEDLINE, Epistemonikos COVID-19,  and the World Health Organization International Clinical Trials Registry Platform were searched for randomized controlled trials (RCTs). The pooled relative risks (RRs) were estimated for dichotomous outcomes with corresponding 95% confidence intervals (CIs) utilizing a random-effect model. Four RCTs (n = 4921) fulfilling the eligibility criteria were identified.

Compared to placebo, hydroxychloroquine use did not minimize the risks of developing coronavirus infection (RR 0.82, moderate certainty), mortality (RR 3.26, low certainty), or hospitalization (RR 0.72, moderate certainty). Furthermore, hydroxychloroquine usage elevated the risk of adverse events (RR 2.76, moderate certainty).

Although pharmacologic prophylaxis is an attractive preventive strategy against severe acute respiratory syndrome coronavirus-2 (SARS CoV-2), hydroxychloroquine failed to show clinical benefit and demonstrated a higher risk of adverse events compared to placebo or no prophylaxis.