• Rob Orman

15. Covid-19: Is There a Case for Hydroxychloroquine?

The short answer is not at the moment, but that hasn't stopped the debate (and surprising culture war) from raging about this drug. A recent opinion piece in Newsweek with the damning title The Key to Defeating COVID-19 Already Exists. We Need to Start Using It written by Yale epidemiology professor Harvey A. Risch, MD, PhD, suggests that we are missing the boat by not widely using hydroxychloroquine (HCQ) and tens of thousands of patients are dying because of it. In addition, he poses that the evidence is clear and the FDA, NIH and others are in effect denying the proof of drug efficacy. What is the data to support these claims?

Dr. Risch wrote an article outlining his argument in the May 27 American Journal of Epidemiology. He cites multiple publications as showing clear evidence of HCQ benefit including:

  • A small French study showing reduction in viral carriage in COVID patients and a shorter carrying duration with HCQ treatment compared to untreated patients. Also, azithromycin added to HCQ was even better for virus elimination.

  • A French case series of over 1000 patients given hydroxychloroquine and azithromycin finding that a low percentage of patients had worsening of disease. There was no comparison group. It was, as is the case in a case series, "We gave it to these people and they did pretty well."

  • An open letter by family practice doctor Vladimir (Zev) Zelenko M.D to "All the physicians of the world" that can be found on this Google Doc. The letter says a combination of HCQ+azithromycin+zinc benefitted outpatients.

  • A Brazilian telemedicine study of patients with COVID symptoms finding a decreased need for hospitalization in those give HCQ compared to not.

  • There's more but that's the jist of it.

Does any of this prove efficacy of HCQ? I'd argue it doesn't, but what it does is give an exciting signal that it might be a fantastic treatment. What we need is higher quality methodology to see if the signal is true or just seductive background noise. And here we go with some higher quality studies from the past few months (and weeks):

  • NEJM June 2020: Post exposure prophylaxis does not prevent COVID infection.

  • NEJM July 2020: HCQ alone or with azithromycin did not improve clinical status at 15 days in mild to moderate COVID infection.

  • Annals Internal Medicine July 2020: Non hospitalized adults with early COVID infection. Change in symptom severity over 14 days did not differ between the HCQ and placebo groups. No significant difference in hospitalizations.

  • RECOVERY Trial: Yet to be published, press release reports no mortality benefit for HCQ in hospitalized patients.

My take home: There was initially signal of great benefit for HCQ in COVID-19 infection. With higher quality studies, however, there has not been a demonstration of benefit for a wide variety of patient types.


  1. Risch, Harvey A. "Early Outpatient Treatment of Symptomatic, High-Risk Covid-19 Patients that Should be Ramped-Up Immediately as Key to the Pandemic Crisis." American Journal of Epidemiology (2020).

  2. Gautret, Philippe, et al. "Hydroxychloroquine and azithromycin as a treatment of COVID-19: results of an open-label non-randomized clinical trial." International journal of antimicrobial agents (2020)

  3. Esper, Rodrigo Barbosa, et al. "Empirical treatment with hydroxychloroquine and azithromycin for suspected cases of COVID-19 followed-up by telemedicine." Prevent Senior Institute SP, Brazil, ed. São Paulo 25 (2020).

  4. Million, Matthieu, et al. "Full-length title: Early treatment of COVID-19 patients with hydroxychloroquine and azithromycin: A retrospective analysis of 1061 cases in Marseille, France." Travel medicine and infectious disease (2020)

  5. Boulware, David R., et al. "A randomized trial of hydroxychloroquine as postexposure prophylaxis for Covid-19." New England Journal of Medicine (2020).

  6. Cavalcanti, Alexandre B., et al. "Hydroxychloroquine with or without Azithromycin in Mild-to-Moderate Covid-19." New England Journal of Medicine (2020).

  7. Skipper, Caleb P., et al. "Hydroxychloroquine in Nonhospitalized Adults With Early COVID-19: A Randomized Trial." Annals of Internal Medicine (2020).

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