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Risk Factors for Hospitalization, Mechanical Ventilation, or Death Among 10 131 US Veterans With SARS-CoV-2 Infection

Educational Objective
To understand the risk factors for hospitalization, mechanical ventilation, or death among 10,131 US Veterans with COVID-19
1 Credit CME
Key Points

Question  What are the risk factors associated with hospitalization, mechanical ventilation, and death among patients with severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection?

Findings  In this national cohort study of 88 747 veterans tested for SARS-CoV-2, hospitalization, mechanical ventilation, and mortality were significantly higher in patients with positive SARS-CoV-2 test results than among those with negative test results. Significant risk factors for mortality included older age, high regional coronavirus disease 2019 burden, higher Charlson Comorbidity Index score, fever, dyspnea, and abnormal results in many routine laboratory tests; however, obesity, Black race, Hispanic ethnicity, chronic obstructive pulmonary disease, hypertension, and smoking were not associated with mortality.

Meaning  In this study, most deaths from SARS-CoV-2 occurred in patients with age of 50 years or older, male sex, and greater comorbidity burden.


Importance  Identifying independent risk factors for adverse outcomes in patients infected with severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) can support prognostication, resource utilization, and treatment.

Objective  To identify excess risk and risk factors associated with hospitalization, mechanical ventilation, and mortality in patients with SARS-CoV-2 infection.

Design, Setting, and Participants  This longitudinal cohort study included 88 747 patients tested for SARS-CoV-2 nucleic acid by polymerase chain reaction between Feburary 28 and May 14, 2020, and followed up through June 22, 2020, in the Department of Veterans Affairs (VA) national health care system, including 10 131 patients (11.4%) who tested positive.

Exposures  Sociodemographic characteristics, comorbid conditions, symptoms, and laboratory test results.

Main Outcomes and Measures  Risk of hospitalization, mechanical ventilation, and death were estimated in time-to-event analyses using Cox proportional hazards models.

Results  The 10 131 veterans with SARS-CoV-2 were predominantly male (9221 [91.0%]), with diverse race/ethnicity (5022 [49.6%] White, 4215 [41.6%] Black, and 944 [9.3%] Hispanic) and a mean (SD) age of 63.6 (16.2) years. Compared with patients who tested negative for SARS-CoV-2, those who tested positive had higher rates of 30-day hospitalization (30.4% vs 29.3%; adjusted hazard ratio [aHR], 1.13; 95% CI, 1.08-1.13), mechanical ventilation (6.7% vs 1.7%; aHR, 4.15; 95% CI, 3.74-4.61), and death (10.8% vs 2.4%; aHR, 4.44; 95% CI, 4.07-4.83). Among patients who tested positive for SARS-CoV-2, characteristics significantly associated with mortality included older age (eg, ≥80 years vs <50 years: aHR, 60.80; 95% CI, 29.67-124.61), high regional COVID-19 disease burden (eg, ≥700 vs <130 deaths per 1 million residents: aHR, 1.21; 95% CI, 1.02-1.45), higher Charlson comorbidity index score (eg, ≥5 vs 0: aHR, 1.93; 95% CI, 1.54-2.42), fever (aHR, 1.51; 95% CI, 1.32-1.72), dyspnea (aHR, 1.78; 95% CI, 1.53-2.07), and abnormalities in the certain blood tests, which exhibited dose-response associations with mortality, including aspartate aminotransferase (>89 U/L vs ≤25 U/L: aHR, 1.86; 95% CI, 1.35-2.57), creatinine (>3.80 mg/dL vs 0.98 mg/dL: aHR, 3.79; 95% CI, 2.62-5.48), and neutrophil to lymphocyte ratio (>12.70 vs ≤2.71: aHR, 2.88; 95% CI, 2.12-3.91). With the exception of geographic region, the same covariates were independently associated with mechanical ventilation along with Black race (aHR, 1.52; 95% CI, 1.25-1.85), male sex (aHR, 2.07; 95% CI, 1.30-3.32), diabetes (aHR, 1.40; 95% CI, 1.18-1.67), and hypertension (aHR, 1.30; 95% CI, 1.03-1.64). Notable characteristics that were not significantly associated with mortality in adjusted analyses included obesity (body mass index ≥35 vs 18.5-24.9: aHR, 0.97; 95% CI, 0.77-1.21), Black race (aHR, 1.04; 95% CI, 0.88-1.21), Hispanic ethnicity (aHR, 1.03; 95% CI, 0.79-1.35), chronic obstructive pulmonary disease (aHR, 1.02; 95% CI, 0.88-1.19), hypertension (aHR, 0.95; 95% CI, 0.81-1.12), and smoking (eg, current vs never: aHR, 0.87; 95% CI, 0.67-1.13). Most deaths in this cohort occurred in patients with age of 50 years or older (63.4%), male sex (12.3%), and Charlson Comorbidity Index score of at least 1 (11.1%).

Conclusions and Relevance  In this national cohort of VA patients, most SARS-CoV-2 deaths were associated with older age, male sex, and comorbidity burden. Many factors previously reported to be associated with mortality in smaller studies were not confirmed, such as obesity, Black race, Hispanic ethnicity, chronic obstructive pulmonary disease, hypertension, and smoking.

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Article Information

Accepted for Publication: August 18, 2020.

Published: September 23, 2020. doi:10.1001/jamanetworkopen.2020.22310

Open Access: This is an open access article distributed under the terms of the CC-BY License. © 2020 Ioannou GN et al. JAMA Network Open.

Corresponding Author: George N. Ioannou, BMBCh, MS, Division of Gastroenterology, Veterans Affairs Puget Sound Healthcare System, 1660 S Columbian Way, Seattle, WA 98108 (georgei@medicine.washington.edu).

Author Contributions: Dr Ioannou had full access to all of the data in the study and takes responsibility for the integrity of the data and the accuracy of the data analysis.

Concept and design: Ioannou, Locke, Green, Berry, O'Hare, Shah, Crothers, Fan.

Acquisition, analysis, or interpretation of data: Ioannou, Locke, Green, Berry, Eastment, Dominitz, Fan.

Drafting of the manuscript: Ioannou, O'Hare.

Critical revision of the manuscript for important intellectual content: All authors.

Statistical analysis: Ioannou, Berry, Eastment.

Obtained funding: Ioannou, Shah.

Administrative, technical, or material support: Locke, Green, Shah.

Supervision: Ioannou, Shah.

Conflict of Interest Disclosures: Dr O’Hare reported receiving grants from the Veterans Affairs Health Services Research and Development, the National Institute of Diabetes and Digestive and Kidney Diseases, the US Centers for Disease Control and Prevention; receiving operations project support from the VA National Center for Ethics in Health Care; and receiving personal fees from UpToDate; Kaiser Permanente Southern California; University of California, San Francisco; University of Pennsylvania; University of Alabama; the Denevir Foundation; Hammersmith Hospital; Dialysis Clinics, Inc; Fresenius Medical Care; Chugai Pharmaceutical Co; the Japanese Society of Dialysis Therapy; and the New York Society of Nephrology outside the submitted work. Dr Fan reported receiving grants from the Department of Veterans Affairs, the Firland Foundation, and the Patient-Centered Outcomes Research Institute outside the submitted work. No other disclosures were reported.

Funding/Support: This study was supported using data from the Veterans Affairs COVID-19 Shared Data Resource. The study was supported in part by the US Department of Veterans Affairs, Office of Research and Development (CSR&D grant, COVID19-8900-11) to Dr Ioannou.

Role of the Funder/Sponsor: The funder had no role in the design and conduct of the study; collection, management, analysis, and interpretation of the data; preparation, review, or approval of the manuscript; and decision to submit the manuscript for publication.

Disclaimer: The contents do not represent the views of the US Department of Veterans Affairs or the US government.

Additional Contributions: We acknowledge the VA Informatics and Computing Infrastructure (VINCI) group, who worked tirelessly to create the COVID-19 Shared Data Resource.

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