According to a large-scale retrospective analysis published in the International Journal of Infectious Diseases, treatment with hydroxychloroquine alone and in combination with  azithromycin was associated with a significant reduction in mortality among patients hospitalized with COVID-19 in a strictly monitored protocol-driven in-hospital setting.

“The benefits of hydroxychloroquine in our cohort as compared to previous studies may be related to its use early in the disease course with standardized, and safe dosing, inclusion criteria, comorbidities, or larger cohort,” Samia Arshad, Henry Ford Hospital, Detroit, Michigan, and colleagues wrote.

The study included patients with a COVID-related admission in the Henry Ford Health System from March 10, 2020 to May 2, 2020. Only the first admission was included for patients with multiple admissions. All patients evaluated were 18 years of age and older and were treated as inpatients for at least 48 hours unless they expired within 24 hours.

The primary objective of the study was to assess treatment with hydroxychloroquine versus hydroxychloroquine plus azithromycin, azithromycin alone, and other treatments for COVID-19. The primary outcome was in-hospital mortality.

In this study, hydroxychloroquine was dosed as 400 mg twice daily for 2 doses on day 1, followed by 200 mg twice daily on days 2-5. Meanwhile, azithromycin was dosed as 500 mg once daily on day 1 followed by 250 mg once daily for the next 4 days. The authors noted that the combination of hydroxychloroquine + azithromycin was reserved for selected patients with severe COVID-19 and with minimal cardiac risk factors. An electrocardiogram (ECK) based algorithm was utilized for hydroxychloroquine use. “QTc>500 ms was considered an elevated cardiac risk and consequently hydroxychloroquine was reserved for patients with severe disease with telemetry monitoring and serial QTc checks,” the authors wrote.

Overall, 2,541 patients, with a median age of 64 years (interquartile range [IQR]: 53-76 years) were included in the analysis. Slightly over half were male and majority of patients (52%, n = 1,250) had BMI ≥ 30. The median time to follow-up was 28.5 days (IQR 3-53).

Results showed that overall in-hospital mortality was 18.1% (95% CI:16.6%-19.7%) . By treatment, 13.5% (95% CI: 11.6%-15.5%) of those given hydroxychloroquine alone died, compared with 20.1% (95% CI: 17.3%-23.0%) for hydroxychloroquine plus azithromycin, 22.4% (95% CI: 16.0%-30.1%) for azithromycin alone and 26.4% (95% CI: 22.2%-31.0%) for those not treated with either drug.

The primary cause of death was respiratory failure, which occurred in 88% of cases. Compared to the group receiving neither hydroxychloroquine nor azithromycin, the authors said hydroxychloroquine provided a 66% decrease in mortality hazard ratio, while hydroxychloroquine plus azithromycin reduced the hazard ratio by 71% (p < 0.001).

The authors noted that the vast majority of patients received hydroxychloroquine soon after admission, with 82% given the drug within 24 hours of admission, and 91% within 48 hours.

In addition, a review of mortality data demonstrated no major cardiac arrhythmias; specifically, no torsades de pointes that has been observed with hydroxychloroquine treatment. The authors explained that this may be due to the fact that the patient population “received aggressive early medical intervention, and were less prone to development of myocarditis, and cardiac inflammation commonly seen in later stages of COVID-19 disease” and that “inpatient telemetry with established electrolyte protocols were stringently applied” to the patient population. They added that monitoring for cardiac dysrhythmias was effective in controlling for adverse events.

“Findings of this observational study provide crucial data on experience with hydroxychloroquine therapy, providing necessary interim guidance for COVID-19 therapeutic practice,” the authors concluded. “However, our results should be interpreted with some caution and should not be applied to patients treated outside of hospital settings,” the authors cautioned. They added that the results require further confirmation in prospective, randomized controlled trials that rigorously evaluate the safety, and efficacy of hydroxychloroquine therapy for COVID-19 in hospitalized patients.