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Risk for In-Hospital Complications Associated with COVID-19 and Influenza — Veterans Health Administration, United States, October 1, 2018–May 31, 2020

Our take —

This study compared clinical complications of SARS-CoV-2 and influenza using two well-defined cohorts of hospitalized adults from the U.S. Veterans Health Administration. Individuals hospitalized with COVID-19, who generally had fewer comorbidities, had worse clinical outcomes (ICU admission and death) and more frequent complications involving multiple organ systems (including respiratory, hematologic, neurologic, and renal complications) as compared to patients hospitalized for influenza. However, differences in clinical-ordered testing and residual confounding may account for some of the observed associations.

Study design

Retrospective cohort

Study population and setting

This study included 5,453 influenza A or B patients diagnosed from October 1, 2018 to February 1, 2020, and 3,948 COVID-19 patients diagnosed from March 1 to May 31, 2020. Patients were drawn from the nationwide U.S. Veterans Health Administration, and identified from, and data on age, sex, race/ethnicity, ICD-10-CM diagnosis codes, and medical follow-up (ICU admission, discharge, death) were extracted. The population was restricted to adults who received a laboratory-confirmed influenza or COVID-19 diagnosis during the first 14 days of hospitalization or in the 30 days preceding hospitalization. Risks of in-hospital complications were compared between influenza and COVID-19 patients.

Summary of Main Findings

Hospitalized COVID-19 patients (n=3,948, 94% male, median age 70 years) had a lower prevalence of most underlying conditions than patients hospitalized with influenza (n=5,453, 94% male, median age 69 years), but had longer hospital stays (8.6 days vs. 3 days), higher rates of ICU admission (36.5% vs. 17.6%), and higher mortality (21% vs. 3.8%). In adjusted analyses, many complications of COVID-19 were slightly more prevalent among racial and ethnic minorities (separately modeled as non-Hispanic Black or African American, Hispanic or Latino, or non-Hispanic other race vs. non-Hispanic White), including intracranial hemorrhage, cerebral ischemia/infarction, pneumonia, respiratory failure, acute respiratory distress syndrome (ARDS), acute kidney failure, dialysis, and sepsis. After adjusting for age, sex, race/ethnicity, and underlying medical conditions, hospitalized patients with COVID-19 (vs. influenza) had a statistically significant increased risk of 17 acute complications involving multiple organ systems (respiratory, cardiovascular, neurologic, renal, etc.). For example, COVID-19 patients had increased risks relative to influenza patients for ARDS (adjusted relative risk (aRR) = 19), pneumothorax (aRR=3.5), pneumonia (aRR=2), and respiratory failure (aRR=1.7), but decreased risk for asthma exacerbation, COPD exacerbation, and hypertensive crisis.

Study Strengths

This was a relatively large study. Controls were drawn from the same underlying population as cases, with the same data collection protocols and similar inclusion criteria, which helps comparability. The authors conducted sensitivity analyses comparing COVID-19 and influenza cases diagnosed during the same months (though from different years) to assess bias from seasonality.


A main concern is whether there are differences in caring for patients with COVID-19 vs. influenza that leads providers to differentially screen for complications during hospitalization. For example, it is plausible that influenza patients receive more clinician-ordered testing for respiratory complications, whereas individuals with COVID-19 are screened more often for a broader range of respiratory and non-respiratory complications, given media and medical attention to the heterogeneous clinical presentation of COVID-19. Additionally, residual confounding is possible due to factors such as geographic location, misclassification of comorbid conditions, and variations in reporting of different complications; these could lead to either under- or over- estimation of the true associations.

Value added

Although the relative severity of influenza and COVID-19 is reasonably well understood, this study provides a detailed look at differences in the frequency of specific severe complications between the two illnesses.

This review was posted on: 2 November 2020