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

Hwanhee Hong, Anne Friedland, Mengyi Hu, Kevin J. Anstrom, Susan Halabi, John E. McKinnon, Ravi Amaravadi, Jorge Rojas-Serrano, Benjamin S. Abella, Angélica Margarita Portillo-Vázquez, Christopher W. Woods, Adrian F. Hernandez, David R. Boulware, Susanna Naggie, Radha Rajasingham

Research output: Contribution to journalArticlepeer-review


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.

Original languageEnglish (US)
Article numbere065305
JournalBMJ open
Issue number6
StatePublished - Jun 16 2023

Bibliographical note

Funding Information:
This study is funded by the Patient Centered Outcomes Research Institute (PCORI; contract number COVID-19-2020-001).

Publisher Copyright:
© Author(s) (or their employer(s)) 2023. Re-use permitted under CC BY-NC. No commercial re-use. See rights and permissions. Published by BMJ.


  • COVID-19
  • epidemiology
  • statistics & research methods

PubMed: MeSH publication types

  • Systematic Review
  • Meta-Analysis
  • Journal Article
  • Research Support, Non-U.S. Gov't


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