More than 200,000 people have died worldwide from the novel coronavirus (COVID-19), and in New York alone, almost 20,000 people have died. Hydroxychloroquine has been considered a potential therapy due to evidence of in vitro studies showing disease suppression in other strains of coronavirus. However, there is little evidence on the efficacy or safety of these alternative uses given the short time since discovery of COVID-19. The objective of this study was to assess how frequently hydroxychloroquine and/or azithromycin are being used in COVID-19 patients and to evaluate if there was any association with mortality or adverse events with their use.
The researchers conducted a retrospective cohort study at 25 metropolitan New York hospitals. Eligible patients presented over a 2-week pre-designated period in March, were admitted for at least 24 hours, and had laboratory confirmed positive COVID-19. These patients were identified by both the State Health Information Network for New York (SHIN-NY) and the New York City Department of Health records. Once the patients were identified, a random sample was taken from each hospital and the electronic health records of these patients were obtained through each hospital. Treatment groups include hydroxychloroquine with azithromycin, hydroxychloroquine only, azithromycin only, or neither treatment. Exclusion criteria include admission period of less than 24 hours, and the chart being too incomplete for review. For all eligible patients, variables gathered included demographics, past medical history, initial vitals, labs, and chest imaging. The primary outcome of interest was in-hospital mortality. Secondary outcomes include presence of electrocardiogram abnormalities and cardiac arrest.
Of 7914 total patients that were diagnosed with COVID-19 and admitted to NY hospitals during the study period, 1438 were randomly selected and included in the analysis. Patients receiving either drug were more likely to be male, but there were no racial differences between drug administration that was observed. Patients receiving hydroxychloroquine were more likely to be obese and have diabetes. Patients receiving both hydroxychloroquine and azithromycin tended to have higher illness severity compared to those receiving neither drug. When adjusted for confounding variables, there were no significant differences in mortality between the three different treatment groups compared to no treatment, with hydroxychloroquine + azithromycin having an adjusted hazard ratio of 1.35 [95% CI, 0.76-2.40], hydroxychloroquine alone having an adjusted HR, 1.08 [95% CI, 0.63-1.85], and azithromycin alone having an adjusted HR, 0.56 [95% CI, 0.26-1.21], compared with neither drug. Regarding secondary outcomes, patients had higher odds of cardiac arrest if they were on hydroxycholorquine and azithromycin compared to neither drug (OR 2.13; [95% CI, 1.12-4.05]) as well as hydroxychloroquine alone vs azithromycin alone (OR 2.97; [95% CI, 1.56-5.64]). There was no statistical difference between the treatment arms and odds of developing abnormal ECG findings.
The authors concluded that the use of hydoxychloroquine, with or without azithromycin, in patients with COVID 19 in New York, did not lead to significant improvement in in-hospital mortality compared to neither treatment.
Comment: This study is limited by the retrospective design and selection bias, as treatments were selected by the physician at the time. While there are many novel therapies being trialed for the treatment of patients with COVID-19, it is important to remember to first, do no harm. Our understanding of COVID-19 is rapidly changing and other published studies have suggested that hydroxychloroquine is not only ineffective, but may also be harmful to patients when used to treat this condition.