• Written By: Damien M Luviano, MD; Kristin Smoot
    Comprehensive Ophthalmology

    Review of: A Randomized Trial of Hydroxychloroquine as Postexposure Prophylaxis for Covid-19

    Boulware D, Pullen M, Bangdiwala A, et al. New England Journal of Medicine, August 6, 2020

    The authors investigated whether hydroxychloroquine can serve as postexposure prophylaxis after interaction with confirmed COVID-19 cases.

    Study design

    Adults in the United States and Canada who had moderate- to high-risk household or occupational exposure to confirmed COVID-19 cases were enrolled in a randomized, double-masked, placebo-controlled trial to test the efficacy of hydroxychloroquine as postexposure prophylaxis within 4 days of exposure. The authors defined exposure as interaction with individuals with confirmed COVID-19 infection at a distance less than 6 feet for greater than 10 minutes without a face mask or eye shield (“high-risk”) or with a face mask but no eye shield (“moderate-risk”). The primary outcome was the incidence of laboratory-confirmed SARS-CoV-2 infection or illness compatible with SARS-CoV-2 within 14 days of initial exposure.


    In the cohort of 821 patients, the authors found no significant difference in the incidence of COVID-19 infection between the hydroxychloroquine group and the placebo group. While no serious adverse reactions were observed in the hydroxychloroquine group, the treatment group experienced a significantly greater proportion of side effects compared to placebo (40.1% vs. 16.8%).


    This study was conducted in a relatively young population cohort (median age 40 years old), which could affect predictive power of this study, particularly given that severe infections associated with increased hospitalizations and higher mortality is more prevalent in older patients. Furthermore, access to diagnostic testing greatly limited this study. The U.S. clinical case definition of probable COVID-19 infection was used to assess incidence in the majority of patients included in this study.

    Clinical significance

    This study suggests that hydroxychloroquine postexposure prophylaxis is not useful for preventing the new incidence of COVID-19 infection, particularly in a relatively young patient group. Since hydroxychloroquine was associated with a greater incidence of side effects without clinical benefit, this study suggests a lack of clinical evidence and a greater harm in prescribing hydroxychloroquine as postexposure prophylaxis. Studies in more at-risk, older populations are ongoing to evaluate whether hydroxychloroquine has greater benefit in these groups.