The WHO’s Living Guideline: Hydroxychloroquine Not Effective for Preventing COVID-19

In the recent WHO guideline, the authors address this critical question: “What is the role of drugs in preventing COVID-19?”

Two organizations strongly recommend against the administration of hydroxychloroquine for the prevention of COVID-19 in people who do not have the infection, according to a recent living guideline developed by the World Health Organization (WHO) and the Magic Evidence Ecosystem Foundation (MAGIC) with support from The BMJ.

Hydroxychloroquine, an immunomodulator used for the treatment of rheumatoid arthritis and systemic lupus erythematosus, has an antiviral effect against several viruses in vitro, including SARS-CoV-2. However, the drug has not shown clinically useful antiviral effects for any viral infections.

To address the uncertainties about which drugs, if any, are effective for the prevention of COVID-19, the guideline panel conducted a living systematic review and network meta-analysis using 6 trials with 6059 participants to produce the recommendations based on the evidence surrounding the use of hydroxychloroquine. Of these studies, 3 enrolled people with known exposure to SARS-CoV-2 infection, and 3 enrolled people who did not have known exposure.

Hydroxychloroquine had little or no effect on mortality or hospital admission, and there was little or no evidence of the drug having an effect on laboratory-confirmed SARS-CoV-2 infection; however, hydroxychloroquine probably increases the risk of adverse events leading to drug discontinuation.

The panel judged that hydroxychloroquine should not be considered worthwhile in COVID-19 prevention and that resources, feasibility, acceptability, and equity for countries and health care systems were not likely to change the recommendation outcome.

Given the consistent trial results, the panel agreed that future research was not likely to uncover any additional subgroup of participants who could benefit from hydroxychloroquine for COVID-19 prevention. More than 80 trials planning to enroll 100,000 individuals are registered or ongoing to assess hydroxychloroquine and chloroquine for COVID-19 prophylaxis.

“The high certainty evidence that has emerged regarding the lack of effect of hydroxychloroquine prophylaxis suggests that funders and researchers should reconsider the initiation or continuation of these trials,” the authors wrote.

Because this is a living guideline, the panel noted that new recommendations will be added for other COVID-19-associated prophylactic drugs.

Additional information on registered and ongoing trials for COVID-19 therapeutics and prophylaxis is available from the Infectious Diseases Data Observatory (through their living systematic review of COVID-19 clinical trial registrations), the WHO, and other repositories such as the COVID-19 Open Living Evidence Synthesis to Inform Decision (COVID-NMA) initiative.


Lamontagne F, Agoritsas T, Siemieniuk R, et al. A living WHO guideline on drugs to prevent COVID-19. BMJ. Published online March 1, 2021. doi:10.1136/bmj.n526