Impact of Prophylactic Hydroxychloroquine on People at High Risk of COVID-19: A Systematic Review and Meta-Analysis

Adrian Vladimir Hernández Diaz, John Ingemi, Michael Sherman, Vinay Pasupuleti, Joshuan J. Barboza, Alejandro Piscoya, Yuani M. Roman, Charles M. White

Research output: Contribution to journalReview articlepeer-review

5 Scopus citations


There are no proven prophylactic interventions for COVID-19. We systematically reviewed the efficacy of prophylactic hydroxychloroquine for COVID-19. Studies evaluating hydroxychloroquine for prophylaxis of COVID-19 were searched in several engines until 8 December 2020. Primary outcomes included RT-PCR positivity, COVID-19 infections (positive RT-PCR or compatible COVID-19 symptoms), and all-cause mortality. Random effects meta-analyses were performed for all outcomes. Five randomized controlled trials (RCTs) (n = 5579) and one cohort (n = 106) were included. Placebo was the comparator in four RCTs, and usual care in one RCT. Compared to the controls, five RCTs showed that hydroxychloroquine prophylaxis did not reduce RT-PCR positivity (RR 1.01, 95% CI 0.88-1.16), COVID-19 infection (RR 0.98, 95% CI 0.78-1.22), or all-cause mortality (RR 0.73, 95% CI 0.27-1.99). There were no differences of effects by pre- or post-exposure prophylaxis. Prophylaxis with hydroxychloroquine increased the risk of diarrhea, abdominal pain, or vomiting (RR 4.56, 95% CI 1.58-13.19). There were no effects of hydroxychloroquine on other secondary outcomes. Quality of evidence was low to very low for all outcomes. Hydroxychloroquine was not efficacious as a prophylaxis for COVID-19 infections, defined either as RT-PCR positivity or as a composite of RT-PCR positivity or compatible symptoms. Hydroxychloroquine did not reduce all-cause mortality, clinical worsening, or adverse events.

Original languageEnglish
Article number2609
Pages (from-to)2609
JournalJournal of Clinical Medicine
Issue number12
StatePublished - 2 Jun 2021


  • COVID-19
  • Efficacy
  • Hydroxychloroquine
  • Prophylaxis
  • Safety


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