COVID-19 Associated with Higher Long-Term Mortality Than Flu or RSV: New Data

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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 new 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-19 versus 0.7% for both influenza and RSV during the 2023-2024 season, reported first author Kristina L. Bajema, MD, of the Veterans Affairs Portland Health Care System in Oregon, and colleagues in JAMA Internal Medicine.

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.

Meanwhile, the 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-19 with either influenza or RSV (risk difference 2.2% and 1.9%, respectively). For the 2023-2024 season, risk patterns were similar, according to the study.

Of note, the mortality risk at 180 days was higher for COVID-19 during both seasons. During the 2022-2023 season, there was an increase in estimated risk difference to 1.1% at 180 days between COVID-19 and both influenza and RSV. During the 2023-2024 season, the mortality risk difference increased to 0.8% between COVID-19 and influenza, and to 0.6% between COVID-19 and RSV, at 180 days.

Veterans were more likely to die from COVID-19 if unvaccinated than to die from influenza 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.

For this study, Bajema and colleagues used the 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 years, and 87% were men.

According the study, updated COVID-19 vaccination was defined as receipt of the bivalent vaccine from September 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 September 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 influenza, and 66.2% had COVID-19. Among 72 939 veterans with an illness in the 2023-2024 season, 13.4% had RSV, 26.4% had influenza, and 60.3% had COVID-19.

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-19, or RSV tended to have higher comorbidity scores and Care Assessment Need Scores than those diagnosed with influenza.

Investigators acknowledged several limitations inherent to the study. Because the analysis was based on VHA data, the findings may not be fully generalizable to the broader US population, given that most veterans are older and predominantly men. Additionally, although the researchers used inverse probability weighting to balance baseline characteristics, residual confounding remains possible. Differential testing practices and the exclusion of veterans with recent prior infections may also have affected the results.

Reference: Bajema KL, Bui DP, Yan L, et al. Severity and long-term mortality of COVID-19, influenza, and respiratory syncytial virus. JAMA Intern Med. Published online January 27, 2025. doi:10.1001/jamainternmed.2024.7452