Treatment with Hydroxychloroquine, Azithromycin, and Combination in Patients Hospitalized with COVID-19

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  • Samia Arshad
  • Paul Kilgore
  • Zohra S. Chaudhry
  • ...
  • Henry Ford COVID-19 Task Force
Journal International Journal of Infectious Diseases
Date July 1, 2020

Retrospective cohort study of 2,541 hospitalized COVID-19 patients in Michigan showed a 66% and 71% hazard ratio reduction for hydroxychloroquine alone and hydroxychloroquine with azithromycin, respectively, compared to standard therapy.

This was one of the largest single hospital system studies in the US to show a significant mortality benefit for hydroxychloroquine in COVID-19 patients.

The study has been challenged based on the usual limitations of retrospective studies as well as a potential difference in treatment goals between the standard therapy and treatment groups. Considering that the standard therapy group had significantly fewer events of intubation or admission to ICU, researchers suspect that a percentage of standard therapy patients may have been palliative with a treatment goal of comfort as opposed to recovery.

Major Issues

The standard therapy group had low rates of ventilation and admission to ICU compared to the hydroxychloroquine treatment groups. Interestingly, despite 108 deaths in the standard therapy group, only 34 and 62 patients received mechanical ventilation or admission to the ICU, respectively. This is surprising as deteriorating patients are often admitted to the ICU or ventilated prior to death. On the other hand, both hydroxychloroquine alone and hydroxychloroquine with azithromycin treatment groups had greater occurrences of ventilation and admission to ICU than the number of deaths. Researchers point to this finding as evidence that patients receiving standard therapy were more likely to be treated with palliative intent where advanced procedures (e.g. ventilation) or novel therapeutics (e.g. hydroxychloroquine) were not utilized.

If a greater percent of standard therapy patients were indeed palliative compared to the other treatment groups, this would be a significant confounding variable that is not addressed in the study.

A significantly greater number of patients treated with hydroxychloroquine also received steroid therapy compared to the standard therapy group (p<0.001). One of the outcomes of the RECOVERY study was the significant mortality benefit to steroid treatment in hospitalized COVID-19 patients. However, it is important to note that the RECOVERY trial only showed a 35% and 20% benefit in patients who were either ventilated or on respiratory support at the time of randomization. There was no benefit in patients who did not require respiratory support. It is unlikely that steroids could account for the entire mortality difference between the hydroxychloroquine and standard therapy groups, however, it may demonstrate a greater benefit for hydroxychloroquine than actually exists.

Minor Issues

No minor issues identified.


This study was one of the first to show a mortality benefit for hydroxychloroquine in a relatively large cohort of US COVID-19 patients.

Article Revisions

None at this time.