COVID-19: Additional evidence links hydroxychloroquine to higher survival

Hydroxychloroquine (HCQ), when used alone or in combination with azithromycin, appears to reduce the mortality associated with COVID-19, according to data published by researchers from the Henry Ford Health System in Detroit, Michigan in the US.

In a cohort of 2,541 patients (median age, 64 years; 51 percent male; 56 percent black), the overall in-hospital mortality was 18.1 percent, which the researchers said reflected a high prevalence of comorbid conditions in COVID-19 patients admitted to their institution.

When assessed by treatment, the proportion of patients who died was 13.5 percent (162 out of 1,202) with HCQ monotherapy and 20.1 percent (157 out of 783) with the combination of HCQ plus azithromycin. These numbers were lower compared with the groups of patients who received azithromycin only (33 out of 147; 22.4 percent) and who were given neither drug (108 out of 409; 26.4 percent). [Int J Infect Dis 2020;doi;10.1016/j.ijid.2020.06.099]

All were treated within 48 hours of admission, with a median total hospitalization time of 6 days. The primary cause of mortality was respiratory failure (88 percent). None of the patients had documented torsades de pointes.

In Cox regression models, predictors of death were older age (≥65 years; hazard ratio [HR], 2.6, 95 percent confidence interval [CI], 1.9–3.3), white race (HR, 1.7, 95 percent CI, 1.4–2.1), chronic kidney disease (HR, 1.7, 95 percent CI, 1.4–2.1), severe illness at initial presentation (reduced oxygen saturation level on admission; HR, 1.5, 95 percent CI, 1.1–2.1), and ventilator use during admission (HR, 2.2, 95 percent CI, 1.4–3.3).

Compared with nonreceipt of both drugs, HCQ cut the risk of death by 66 percent and the HCQ–azithromycin combo by 71 percent (p<0.001).

To date, the current evidence about the efficacy of using HCQ to treat patients with COVID-19 is conflicting. Use of the drug has been shown to lead to a faster resolution of fever, cough, and pneumonia in patients from China in a randomized controlled study. In contrast, there was no survival benefit seen in more than 2,000 patients from New York in the US in two separate cohort studies. [MedRxiv 2020;doi:10.1101/2020.03.22.20040758; N Engl J Med 2020;382:2411-2418; JAMA 2020;323:2493-2502]

“The benefits of HCQ 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,” according to the researchers.

Citing the postulated COVID-19 pathophysiology of the initial viral infection phase followed by the hyperimmune response for the potential benefit of early HCQ administration, they explained: “Later therapy in patients that have already experienced hyperimmune response or critical illness is less likely to be of benefit. Others have shown that … hospitalized patients are not diagnosed in the community and often rapidly deteriorate when hospitalized with fulminant illness.” [Baylor Univ Med Center Proc 2020;doi:10.1080/08998280.2020.1762439]

The researchers believe that the findings provide crucial data on experience with HCQ therapy and may be used as an interim guidance for COVID-19 therapeutic practice, in addition to supporting the recent National Institutes of Health guidelines, which indicate a potential role for HCQ for treating hospitalized COVID-19 patients without co-administration of azithromycin. [https://covid19treatmentguidelines.nih.gov/therapeutic-options-under-investigation/]

“However, our results should be interpreted with some caution and should not be applied to patients treated outside of hospital settings. [They] also require further confirmation in prospective, randomized controlled trials that rigorously evaluate the safety and efficacy of HCQ therapy for COVID-19 in hospitalized patients,” the researchers added.

In late March, the US Food and Drug Administration issued an emergency use authorization (EUA) for HCQ in the treatment of COVID-19 patients. The agency revoked this EUA in June, citing concerns about efficacy and risks related to the use of the drug. [https://www.fda.gov/media/136534/download; https://www.fda.gov/news-events/press-announcements/coronavirus-covid-19-update-fda-revokes-emergency-use-authorization-chloroquine-and]