Treatment with hydroxychloroquine, azithromycin, and combination in patients hospitalized with COVID-19
Samia Arshad, Paul Kilgore, Zohra S Chaudhry, Gordon Jacobsen, Dee Dee Wang, Kylie Huitsing, Indira Brar, George J Alangaden, Mayur S Ramesh, John E Mckinnon, William O’neill, Marcus Zervos, Varidhi Nauriyal, Asif Abdul Hamed, Owais Nadeem, Jennifer Swiderek, Amanda Godfrey, Jeffrey Jennings, Jayna Gardner-Gray, Adam M Ackerman, Jonathan Lezotte, Joseph Ruhala, Raef Fadel, Amit Vahia, Smitha Gudipati, Tommy Parraga, Anita Shallal, Gina Maki, Zain Tariq, Geehan Suleyman, Nicholas Yared, Erica Herc, Johnathan Williams, Odaliz Abreu Lanfranco, Pallavi Bhargava, Katherine Reyes
International Journal of Infectious Diseases, doi:10.1016/j.ijid.2020.06.099
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 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.
Conflict of interest S.H. received speakers' bureau honoraria from Bayer. I.B. received speakers' bureau honoraria from Gilead, ViiV, and Jansssen, M.Z received consultation honoraria from contrafact. All others have no conflicts of interests.
Ethical approval Approval for this study was granted by the Henry Ford Hospital Institutional Review Board (#13897).
Appendix A Henry Ford COVID-19 Task Force: Varidhi Nauriyal, MD a,b , Asif Abdul Hamed, MD b , Owais Nadeem, MD b , Jennifer Swiderek, MD b , Amanda Godfrey, MD b , Jeffrey Jennings, MD b , Jayna Gardner-Gray, MD c , Adam M. Ackerman, MD d , Jonathan Lezotte, DO d , Joseph Ruhala, DO d , Raef Fadel, DO e , Amit Vahia, MD, MPH a , Smitha Gudipati, MD a , Tommy Parraga, MD a , Anita Shallal, MD a , Gina Maki, DO a , Zain Tariq, MD a , Geehan Suleyman, MD a , Nicholas Yared, MD a , Erica Herc, MD a , Johnathan Williams, MD a , Odaliz Abreu Lanfranco, MD a , Pallavi Bhargava, MD a , Katherine Reyes, MD, MPH a , Anne Chen, MD
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