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SARS-CoV-2 infection was associated with more severe disease outcomes than influenza or respiratory syncytial virus (RSV) during the 2022-2023 respiratory illness season, while differences were less striking during the 2023-2024 season, according to a retrospective cohort study of veterans.

The 30-day risk of death during the 2022-2023 season was 1.0% for COVID-19 compared with 0.7% for both influenza and RSV, and 0.9% for COVID versus 0.7% for both flu and RSV during the 2023-2024 season, reported Kristina L. Bajema, MD, of the Veterans Affairs Portland Health Care System in Oregon, and colleagues.

The 30-day risks of hospitalization were 17.5%, 15.9%, and 14.4% for COVID, influenza, and RSV, respectively, during the 2022-2023 season, and 16.2%, 16.3%, and 14.3%, respectively, during the 2023-2024 season, they noted in JAMA Internal Medicine.

Meanwhile, risk of 30-day intensive care unit (ICU) admission during the 2022-2023 season was similar when comparing influenza and RSV (risk difference -0.3%) and higher when comparing COVID with either influenza or RSV (risk difference 2.2% and 1.9%, respectively). For the 2023-2024 season, risk patterns were similar.

Of note, mortality risk at 180 days was higher for COVID during both seasons. During the 2022-2023 season, there was an increase in estimated risk difference to 1.1% at 180 days between COVID and both flu and RSV. During the 2023-2024 season, the mortality risk difference increased to 0.8% between COVID and influenza, and to 0.6% between COVID and RSV, at 180 days.

Veterans were more likely to die from COVID if unvaccinated than to die from flu if unvaccinated, but mortality rates were similar when they were vaccinated against the illness they had.

“Vaccination remains an important strategy for minimizing the impact of [respiratory viral illnesses] and particularly Omicron variants,” Bajema and team concluded.

William Schaffner, MD, of Vanderbilt University Medical Center in Nashville, Tennessee, told MedPage Today that the study “demonstrates that COVID continues to be a serious infection in this population, causing more serious illnesses and deaths than infections caused by influenza and RSV.”

“Importantly, it also showed that vaccination reduced the risks of serious, life-threatening disease,” he added. “It is a timely reminder that vaccination against all these respiratory viruses — COVID, influenza, and RSV — can prevent illness and save lives.”

For this study, Bajema and colleagues used national Veterans Health Administration electronic health record data for non-hospitalized veterans who underwent same-day testing for SARS-CoV-2, influenza, and RSV, and were diagnosed with a single infection between August 2022 and March 2023, or between August 2023 and March 2024. Median age was 66, and 87% were men.

Updated COVID vaccination was defined as receipt of the bivalent vaccine from Sept. 1, 2022 through 7 days prior to the index date during the 2022-2023 season and receipt of the monovalent XBB.1.5 vaccine from Sept. 12, 2023 through 7 days prior to the index date during the 2023-2024 season. For influenza, vaccination was defined as receipt of any same-season influenza vaccine from August 1 through 14 days prior to the index date. Vaccination for RSV was rare, and was not included in the vaccinated subgroup analysis.

Among the 68,581 veterans with a respiratory illness in the 2022-2023 season, 9.1% had RSV, 24.7% had flu, and 66.2% had COVID. Among 72,939 veterans with an illness in the 2023-2024 season, 13.4% had RSV, 26.4% had flu, and 60.3% had COVID.

Starting on the first day of a positive test, the researchers tracked all-cause 30-day hospitalization, ICU admission, and death at 30, 90, and 180 days.

Most veterans were diagnosed in the emergency department or urgent care, ranging from 68% to 76% depending on the virus and season. Those diagnosed with COVID or RSV tended to have higher comorbidity scores and Care Assessment Need Scores than those diagnosed with flu.