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Research Article: Safety and efficacy of hydroxychloroquine as prophylactic against COVID-19 in healthcare workers: a meta-analysis of randomised clinical trials

Date Published: 2023-06-16

Abstract:
Objective We studied the safety and efficacy of hydroxychloroquine (HCQ) as pre-exposure prophylaxis for COVID-19 in healthcare workers (HCWs), using a meta-analysis of randomised controlled trials (RCTs). Data sources PubMed and EMBASE databases were searched to identify randomised trials studying HCQ. Study selection Ten RCTs were identified (n=5079 participants). Data extraction and synthesis The Preferred Reporting Items for Systematic Reviews and Meta-Analyses guidelines were used in this systematic review and meta-analysis between HCQ and placebo using a Bayesian random-effects model. A pre-hoc statistical analysis plan was written. Main outcomes The primary efficacy outcome was PCR-confirmed SARS-CoV-2 infection and the primary safety outcome was incidence of adverse events. The secondary outcome included clinically suspected SARS-CoV-2 infection. Results Compared with placebo, HCWs randomised to HCQ had no significant difference in PCR-confirmed SARS-CoV-2 infection (OR 0.92, 95% credible interval (CI): 0.58, 1.37) or clinically suspected SARS-CoV-2 infection (OR 0.78, 95%?CI: 0.57, 1.10), but significant difference in adverse events (OR 1.35, 95%?CI: 1.03, 1.73). Conclusions and relevance Our meta-analysis of 10 RCTs investigating the safety and efficacy of HCQ as pre-exposure prophylaxis in HCWs found that compared with placebo, HCQ does not significantly reduce the risk of confirmed or clinically suspected SARS-CoV-2 infection, while HCQ significantly increases adverse events. PROSPERO registration number CRD42021285093.

Introduction:
Early during the SARS-CoV-2 pandemic, based on in vitro antiviral activity of both chloroquine and hydroxychloroquine (HCQ) against SARS-CoV-2, 1–3 clinicians considered use of HCQ for treatment and prevention of SARS-CoV-2 infection and the associated disease, COVID-19. While there are now published randomised controlled trials (RCTs) of HCQ for the treatment of COVID-19 in the inpatient and outpatient setting, 4 5 there remains a lack of adequately powered RCTs of HCQ for the pre-exposure prophylaxis (PrEP) of…

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