Treatment with hydroxychloroquine, azithromycin, and combination in patients hospitalized with COVID-19

Document Type

Article

Publication Date

8-1-2020

Publication Title

International journal of infectious diseases

Abstract

SIGNIFICANCE: The United States is in an acceleration phase of the COVID-19 pandemic. Currently there is no known effective therapy or vaccine for treatment of SARS-CoV-2, highlighting urgency around identifying effective therapies.

OBJECTIVE: The purpose of this study was to evaluate the role of hydroxychloroquine therapy alone and in combination with azithromycin in hospitalized patients positive for COVID-19.

DESIGN: Multi-center retrospective observational study.

SETTING: The Henry Ford Health System (HFHS) in Southeast Michigan: large six hospital integrated health system; the largest of hospitals is an 802-bed quaternary academic teaching hospital in urban Detroit, Michigan.

PARTICIPANTS: Consecutive patients hospitalized with a COVID-related admission in the health system from March 10, 2020 to May 2, 2020 were included. 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 48h unless expired within 24h.

EXPOSURE: Receipt of hydroxychloroquine alone, hydroxychloroquine in combination with azithromycin, azithromycin alone, or neither.

MAIN OUTCOME: The primary outcome was in-hospital mortality.

RESULTS: Of 2,541 patients, with a median total hospitalization time of 6 days (IQR: 4-10 days), median age was 64 years (IQR:53-76 years), 51% male, 56% African American, with median time to follow-up of 28.5 days (IQR:3-53). Overall in-hospital mortality was 18.1% (95% CI:16.6%-19.7%); by treatment: hydroxychloroquine+azithromycin, 157/783 (20.1% [95% CI: 17.3%-23.0%]), hydroxychloroquine alone, 162/1202 (13.5% [95% CI: 11.6%-15.5%]), azithromycin alone, 33/147 (22.4% [95% CI: 16.0%-30.1%]), and neither drug, 108/409 (26.4% [95% CI: 22.2%-31.0%]). Primary cause of mortality was respiratory failure (88%); no patient had documented torsades de pointes. From Cox regression modeling, predictors of mortality were age>65 years (HR:2.6 [95% CI:1.9-3.3]), white race (HR:1.7 [95% CI:1.4-2.1]), CKD (HR:1.7 [95%CI:1.4-2.1]), reduced O2 saturation level on admission (HR:1.5 [95%CI:1.1-2.1]), and ventilator use during admission (HR: 2.2 [95%CI:1.4-3.3]). Hydroxychloroquine provided a 66% hazard ratio reduction, and hydroxychloroquine+azithromycin 71% compared to neither treatment (p<0.001).

CONCLUSIONS AND RELEVANCE: In this multi-hospital assessment, when controlling for COVID-19 risk factors, treatment with hydroxychloroquine alone and in combination with azithromycin was associated with reduction in COVID-19 associated mortality. Prospective trials are needed to examine this impact.

Medical Subject Headings

Aged; Azithromycin; Betacoronavirus; Coronavirus Infections; Drug Therapy, Combination; Female; Hospital Mortality; Hospitalization; Humans; Hydroxychloroquine; Inpatients; Male; Middle Aged; Pandemics; Pneumonia, Viral; Retrospective Studies; Risk Factors

PubMed ID

32623082

ePublication

ePub ahead of print

Volume

97

First Page

396

Last Page

403

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