Can hydroxychloroquine prevent COVID-19?

In the early days of the first wave of the COVID-19 pandemic, doctors in Canada and the U.S cooperated and launched a randomized, double-blind, placebo-controlled trial of hydroxychloroquine to assess its potential to prevent the development of COVID-19. Participants were adults who may have been exposed to SARS-CoV-2 via contact with an infected person at home or at work.

Overall, 821 people were enrolled and began taking the study pills (drug or placebo) within four days of potential exposure to the virus. There was no statistically significant difference in the proportions of people who developed COVID-19: 12% of people on HCQ and 14% of people who received placebo. Side effects were more common in people who received HCQ (40%) than in people on placebo (17%).

Study details

The average profile of participants upon entering the study was as follows:

  • age – 40 years
  • 50% men, 50% women
  • 67% were healthcare workers
  • co-existing health condition – 73% had none of the underlying health conditions associated with increased susceptibility to COVID-19. However, smaller proportions had higher-than-normal blood pressure (12%), asthma (8%) or diabetes (4%). (Percentages do not total 100 due to rounding.)


The proportions of people who developed COVID-19 did not differ by the drug/placebo they used.

Four infectious disease experts reviewed the symptoms of people who developed them to reach consensus as to whether or not these people had COVID-19. The trial was done in the early part of the COVID-19 epidemic and there was a shortage of tests for SARS-CoV-2. Therefore, most people were diagnosed based on their symptoms and not viral assays.

Adherence to the study regimens was self-assessed and was reported as follows:

  • HCQ – 75% of participants took all of their pills over the course the study
  • placebo – 83% of participants took all of their pills over the course of the study

The study team stated that the most common reason that participants stopped taking their pills was “side effects.” Common side effects were “nausea, loose stools and abdominal discomfort.”

Bear in mind

It is a major accomplishment to have conducted a randomized clinical trial of HCQ for the prevention of COVID-19 relatively early in the course of the pandemic.

Participants were rapidly recruited from across North America; this increases the generalizability of the study results. However, participants were relatively young and many did not have the underlying conditions usually seen in hospitalized people with COVID-19. This may reduce the applicability of the study’s findings in people at high risk of hospitalization due to COVID-19.

The study was not reliant on viral tests to diagnose SARS-CoV-2 infection; as mentioned, there was a shortage of tests at the time the study was done. However, this means that doctors cannot be certain how many people ultimately became infected with the virus. Note that a large proportion of people who become infected with SARS-CoV-2 do not have symptoms of infection or develop symptoms of COVID-19.

Commenting on the study in The New England Journal of Medicine, infectious disease specialist Myron Cohen, MD, notes that it is possible that what the trial inadvertently assessed was “prevention of symptoms or progression of COVID-19 in people who became infected, rather than prevention of SARS-CoV-2 infection.”

Due to these concerns, it is important that other randomized controlled trials of HCQ to prevent and treat SARS-CoV-2 infection continue so that definitive evidence can be found about the potential value of this drug.

—Sean R. Hosein


  1. Boulware DR, Pullen MF, Bangdiwala AS, et al. A randomized trial of hydroxychloroquine as postexposure prophylaxis for Covid-19. New England Journal of Medicine. 2020; in press.
  2. Cohen MS. Hydroxychloroquine for the prevention of Covid-19 – Searching for evidence. Editorial. New England Journal of Medicine. 2020; in press.