Article Text

Original research
Safety and efficacy of hydroxychloroquine as prophylactic against COVID-19 in healthcare workers: a meta-analysis of randomised clinical trials
  1. Hwanhee Hong1,2,
  2. Anne Friedland3,
  3. Mengyi Hu1,
  4. Kevin J Anstrom4,
  5. Susan Halabi2,5,
  6. John E McKinnon6,
  7. Ravi Amaravadi7,
  8. Jorge Rojas-Serrano8,
  9. Benjamin S Abella7,
  10. Angélica Margarita Portillo-Vázquez9,
  11. Christopher W Woods2,
  12. Adrian F Hernandez2,
  13. David R Boulware10,
  14. Susanna Naggie2,
  15. Radha Rajasingham10
  1. 1Department of Biostatistics and Bioinformatics, Duke University, Durham, North Carolina, USA
  2. 2Duke Clinical Research Institute, Durham, North Carolina, USA
  3. 3Department of Infectious Disease, UNC School of Medicine, Chapel Hill, North Carolina, USA
  4. 4Collaborative Studies Coordinating Center, University of North Carolina System, Chapel Hill, North Carolina, USA
  5. 5Department of Biostatistics and Bioinformatics, Duke University School of Medicine, Durham, North Carolina, USA
  6. 6Division of Infectious Diseases, Henry Ford Hospital, Detroit, Michigan, USA
  7. 7Division of Hematology Oncology, University of Pennsylvania, Philadelphia, Pennsylvania, USA
  8. 8Interstitial Lung Disease and Rheumatology Units, Instituto Nacional de Enfermedades Respiratorias, Mexico City, Mexico
  9. 9Otolaryngology Department, Instituto Nacional de Enfermedades Respiratorias, Mexico City, Mexico
  10. 10Division of Infectious Diseases & International Medicine, University of Minnesota Twin Cities, Minneapolis, Minnesota, USA
  1. Correspondence to Dr Hwanhee Hong; hwanhee.hong{at}


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.

  • COVID-19
  • statistics & research methods
  • epidemiology

Data availability statement

All data relevant to the study are included in the article or uploaded as supplemental information.

This is an open access article distributed in accordance with the Creative Commons Attribution Non Commercial (CC BY-NC 4.0) license, which permits others to distribute, remix, adapt, build upon this work non-commercially, and license their derivative works on different terms, provided the original work is properly cited, appropriate credit is given, any changes made indicated, and the use is non-commercial. See:

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Data availability statement

All data relevant to the study are included in the article or uploaded as supplemental information.

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  • Contributors HH, SN, RR and KJA designed the study. HH is the guarantor. HH, AF and MH collected and analysed the data. HH, SN and RR wrote the manuscript. SH and KJA provided statistical review, while AF, JEM, RA, JR-S, BSA, AMP-V, CWW, AFH and DRB provided clinical review. All authors approved and decided to submit the paper for publication.

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

  • Disclaimer The funder had no role in the design, conduct, analysis or reporting of this study.

  • Competing interests All authors except BSA reported no financial relationship with commercial interest. BSA has received NIH funds for COVID-19-related research and holds equity in VOC Health, a start-up company that is developing novel COVID-19 testing.

  • Patient and public involvement Patients and/or the public were not involved in the design, or conduct, or reporting, or dissemination plans of this research.

  • Provenance and peer review Not commissioned; externally peer reviewed.

  • Supplemental material This content has been supplied by the author(s). It has not been vetted by BMJ Publishing Group Limited (BMJ) and may not have been peer-reviewed. Any opinions or recommendations discussed are solely those of the author(s) and are not endorsed by BMJ. BMJ disclaims all liability and responsibility arising from any reliance placed on the content. Where the content includes any translated material, BMJ does not warrant the accuracy and reliability of the translations (including but not limited to local regulations, clinical guidelines, terminology, drug names and drug dosages), and is not responsible for any error and/or omissions arising from translation and adaptation or otherwise.