dcyphr | A Randomized Trial of Hydroxychloroquine as Postexposure Prophylaxis for COVID-19


Whether hydroxychloroquine can prevent infection after exposure to SARS-CoV-2 is unknown. In this study, the researchers conducted a randomized, double-blind, placebo-controlled trial in the U.S. and Canada. They tested hydroxychloroquine’s ability to prevent infection after exposure to SARS-CoV-2. Participants in the study were adults who had exposure to someone with COVID-19 at a distance of less than 6 feet for more than 10 minutes with little protection. After exposure, participants received a placebo or hydroxychloroquine. The researchers assessed whether the participants developed laboratory-confirmed COVID-19 or illness that indicated COVID-19 within 14 days. The researchers found that the incidence of COVID-19 did not differ significantly between participants receiving hydroxychloroquine and participants receiving placebo. Side effects were also more common with hydroxychloroquine than placebo. In conclusion, hydroxychloroquine did not prevent COVID-19 after exposure.


The researchers wanted to understand whether hydroxychloroquine can prevent infection after exposure to the SARS-CoV-2 virus.


SARS-CoV-2 is the virus that causes COVID-19. While there are public health strategies to decrease its transmission, there is no medication that prevents SARS-CoV-2 transmission and infection.

Hydroxychloroquine has in vitro (outside of a living organism, such as a test tube) activity against SARS-CoV and SARS-CoV-2. It is thought to impair activity of the angiotensin-converting-enzyme 2 (ACE2) receptor. This prevents binding of viruses to host cells.

Clinical studies of hydroxychloroquine for COVID-19 have focused on treating hospitalized patients. However, it is also important to prevent transmission to inhibit the spread of the pandemic. Previous research suggested that hydroxyquinolone use could reduce or even eliminate the risk of transmission. In this study, the researchers hypothesize that hydroxyquinolone could be used to prevent infections after exposure to SARS-CoV-2.


The researchers conducted a randomized, double-blind, placebo-controlled trial. They randomly assigned participants to receive either hydroxychloroquine or placebo. Participants had known exposure to SARS-CoV-2.

The researchers included participants who had household or occupational exposure to a person with confirmed COVID-19 at a distance of less than 6 feet for more than 10 minutes with little protection (no face mask, or face mask but no eye shield).

Recruitment of participants was done by social media outreach and other media platforms.

Hydroxychloroquine sulfate or placebo was dispensed and delivered to participants. The dosing for hydroxychloroquine was 800mg once, then 600mg 6-8 hours later, and 600mg daily for 4 more days. Placebo tablets were similar in appearance to hydroxychloroquine tablets and were prescribed in an identical manner.

The primary outcome studied was laboratory-confirmed COVID-19 or COVID-19-related symptoms if testing was unavailable. Secondary outcomes included hospitalization for COVID-19 or death, PCR-confirmed SARS-CoV-2 infection, discontinuation of medication, and severity of symptoms. Data about side effects were also collected.

Statistics were used to calculate ideal sample size and assess the incidence of COVID-19 disease.



The researchers recruited 821 asymptomatic adult participants. 414 were assigned to the hydroxychloroquine group and 407 were assigned to the placebo group. Overall, 719 participants had high-risk exposures to SARS-CoV-2. Of these, 365 received hydroxychloroquine, and 354 received placebo.

Primary outcome

Overall, COVID-19 developed in 107 of 821 participants. The incidence of COVID-19 did not differ between those receiving hydroxychloroquine (49 out of 414) and those receiving placebo (58 of 407).

Adherence and safety

Adherence to medication in the trial participants was moderate. 75.4% of participants in the hydroxychloroquine group and 82.6% of those in the placebo group took all prescribed medication. The most common reason that participants stopped taking medication in the hydroxychloroquine group was side effects. Side effects were more common with hydroxychloroquine than placebo.

Blinding was well-maintained in the absence of side-effects. Participants who reported any side effect were likely to believe they received hydroxychloroquine.


In this study, the researchers investigated the efficacy of hydroxychloroquine in preventing symptomatic infection of SARS-CoV-2.

The researchers’ approach using internet-based self-referral and online follow-up surveys allowed recruitment across the U.S and Canada, indicating broad geographic participation and high generalizability to the general population. It also minimized risk of infection to researchers and lowered the burden of research participation. A result of this approach was that participants were generally younger and healthier than those more at-risk for severe COVID-19. 

In addition, while PCR or serologic testing for asymptomatic infection would have strengthened the study, it was not possible. Thus, more research should be done to investigate the effect of hydroxychloroquine on mild or asymptomatic infections. However, the risks associated with hydroxychloroquine may increase in more at-risk populations and could negate any benefits.

The researchers acknowledge that this trial has limitations. Reproduction of the researchers’ results in other, ongoing trials is necessary to confirm their findings.