Hydroxychloroquine and Azithromycin use in COVID-19 :Final chapter is not written yet
Over the last few months several studies has shown conflicting efficacy and safety of Hydroxychloroquine (HCQ) alone or in association with azithromycin or Doxycycline. Most recent data now published in International Journal of Infectious Diseases showing mortality benefit of HCQ alone or in association with Azithromycin in the treatment of COVID-19. In this observational study from the Henry Ford Health System in Detroit, investigators examined the in-hospital mortality of 2,541 consecutive hospitalized COVID-19 patients in four treatment categories: hydroxychloroquine (HCQ) plus azithromycin (AZM), either drug alone, or neither drug. They excluded patients who died in the first 24 hours after admission and another 10% of patients for whom final outcome data were unavailable (e.g., still hospitalized, left against medical advice, or transferred to another facility). The median time to follow-up was 28.5 days. Overall in-hospital mortality was 18.1% (95% CI, 16.6% to 19.7%). Mortality for patients taking HCQ+AZM was 20.1% (95% CI, 17.3% to 23.0%); for HCQ alone, 13.5% (95% CI, 11.6% to 15.5%); for AZM alone, 22.4% (95% CI, 16.0% to 30.1%); and neither drug, 26.4% (95% CI, 22.2% to 31.0%). In the Cox regression analysis that adjusted for age, gender, comorbid conditions, and disease severity, the hazard ratio for mortality was reduced 66% (p < 0.001) compared with the group receiving neither HCQ nor AZM. The authors report wide variations in the use of corticosteroids among the different treatment groups: 36% in those treated with neither medication, 39% of those receiving AZM alone, 74% of those treated with both, and 79% of those receiving HCQ alone. This is an observational study. These kinds of studies can find associations but are fairly weak in determining a causal link between an exposure and an outcome. In this study, the findings are inconsistent with other observational studies and with data we have from the few randomized trials that exist. Additionally, they found no effect of steroids in the outcome, which is at odds with other studies (e.g., see Research Brief from June 30 on the effects of dexamethasone from the RECOVERY Collaborative Group), at least in those with severe COVID. Observational studies are subject to all kinds of bias and are subject to alternative explanations for the findings. For example, about 25% of the patients had missing measures of disease severity and were excluded from the regression model. The co-treatment with steroids is likely to reflect differences in disease severity. Observational studies are also unable to account for the “hidden” factors involved in how physicians decide the treatments they choose based on other patient characteristics. Finally, the regression analysis took into account only factors the authors chose and could not address residual confounding. In a randomized trial, the known and unknown factors associated with the outcome of interest are evenly distributed between the intervention groups. Source: Arshad S, Kilgore P, Chaudhry ZS, et al.; Henry Ford COVID-19 Task Force. Treatment with hydroxychloroquine, azithromycin, and combination in patients hospitalized with COVID-19 [published online July 1, 2020]. Int J Infect Dis. https://www.ijidonline.com/article/S1201-9712(20)30534-8/fulltext(www.ijidonline.com))