|dc.description.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
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; thelargest ofhospitals is an 802-bed quaternaryacademic teachinghospital inurban 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 48 h unless expired within 24 h.
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.
© 2020 The Author(s). Published by Elsevier Ltd on behalf of International Society for Infectious Diseases.
This is an open access article under the CC BY-NC-ND license (http://creativecommons.org/licenses/by-ncnd/4.0/).||spa