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Treatment with hydroxychloroquine, azithromycin, and combination in patients hospitalized with COVID-19.
Int J Infect Dis. 2020 Aug; 97:396-403.IJ

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.

Authors+Show Affiliations

Infectious Diseases, Henry Ford Hospital, Detroit, MI, United States.Eugene Applebaum College of Pharmacy, Wayne State University, Detroit, MI, United States; Wayne State University School of Medicine, Detroit, MI, United States.Infectious Diseases, Henry Ford Hospital, Detroit, MI, United States.Public Health Sciences, Henry Ford Hospital, Detroit, MI, United States.Division of Cardiovascular Disease & Structural Heart, Henry Ford Hospital, Detroit, MI, United States.Infectious Diseases, Henry Ford Hospital, Detroit, MI, United States.Infectious Diseases, Henry Ford Hospital, Detroit, MI, United States.Infectious Diseases, Henry Ford Hospital, Detroit, MI, United States; Wayne State University School of Medicine, Detroit, MI, United States.Infectious Diseases, Henry Ford Hospital, Detroit, MI, United States.Infectious Diseases, Henry Ford Hospital, Detroit, MI, United States.Division of Cardiovascular Disease & Structural Heart, Henry Ford Hospital, Detroit, MI, United States.Infectious Diseases, Henry Ford Hospital, Detroit, MI, United States; Wayne State University School of Medicine, Detroit, MI, United States. Electronic address: MZervos1@hfhs.org.No affiliation info available

Pub Type(s)

Journal Article
Multicenter Study
Observational Study

Language

eng

PubMed ID

32623082

Citation

Arshad, Samia, et al. "Treatment With Hydroxychloroquine, Azithromycin, and Combination in Patients Hospitalized With COVID-19." International Journal of Infectious Diseases : IJID : Official Publication of the International Society for Infectious Diseases, vol. 97, 2020, pp. 396-403.
Arshad S, Kilgore P, Chaudhry ZS, et al. Treatment with hydroxychloroquine, azithromycin, and combination in patients hospitalized with COVID-19. Int J Infect Dis. 2020;97:396-403.
Arshad, S., Kilgore, P., Chaudhry, Z. S., Jacobsen, G., Wang, D. D., Huitsing, K., Brar, I., Alangaden, G. J., Ramesh, M. S., McKinnon, J. E., O'Neill, W., & Zervos, M. (2020). Treatment with hydroxychloroquine, azithromycin, and combination in patients hospitalized with COVID-19. International Journal of Infectious Diseases : IJID : Official Publication of the International Society for Infectious Diseases, 97, 396-403. https://doi.org/10.1016/j.ijid.2020.06.099
Arshad S, et al. Treatment With Hydroxychloroquine, Azithromycin, and Combination in Patients Hospitalized With COVID-19. Int J Infect Dis. 2020;97:396-403. PubMed PMID: 32623082.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - Treatment with hydroxychloroquine, azithromycin, and combination in patients hospitalized with COVID-19. AU - Arshad,Samia, AU - Kilgore,Paul, AU - Chaudhry,Zohra S, AU - Jacobsen,Gordon, AU - Wang,Dee Dee, AU - Huitsing,Kylie, AU - Brar,Indira, AU - Alangaden,George J, AU - Ramesh,Mayur S, AU - McKinnon,John E, AU - O'Neill,William, AU - Zervos,Marcus, AU - ,, Y1 - 2020/07/02/ PY - 2020/5/28/received PY - 2020/6/22/revised PY - 2020/6/29/accepted PY - 2020/7/6/pubmed PY - 2020/7/31/medline PY - 2020/7/6/entrez KW - COVID-19 KW - Coronavirus KW - Hydroxychloroquine KW - Mortality KW - SARS-COV-2 KW - Therapy SP - 396 EP - 403 JF - International journal of infectious diseases : IJID : official publication of the International Society for Infectious Diseases JO - Int J Infect Dis VL - 97 N2 - 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. SN - 1878-3511 UR - https://www.unboundmedicine.com/medline/citation/32623082/Treatment_with_hydroxychloroquine_azithromycin_and_combination_in_patients_hospitalized_with_COVID_19_ DB - PRIME DP - Unbound Medicine ER -