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Hospitalization for COVID-19 was associated with higher long-term risks of mortality, adverse health outcomes, and significant cumulative excess disability-adjusted life-years (DALYs) than hospitalization for seasonal influenza, according to a new study.

“Although rates of death and adverse health outcomes following hospital admission for either seasonal influenza or COVID-19 are high, this comparative analysis shows that hospital admission for COVID-19 was associated with higher long-term risks of death and adverse health outcomes in nearly every organ system (except for the pulmonary system) and significant cumulative excess DALYs than hospital admission for seasonal influenza,” wrote researchers in The Lancet Infectious Diseases.

Although previous comparative analyses of individuals hospitalized for COVID-19 compared to seasonal influenza have examined the risk of death, hospital admission, and health outcomes up to 6 months after infection, “the comparative risks and burdens of death and health-care resource utilization beyond 6 months after infection are largely unknown,” wrote first author Yan Xie, PhD, of the VA Saint Louis Health Care System in Saint Louis, Missouri, and colleagues.

Investigators conducted the current cohort study to compare both acute and long-term risks and burdens associated with hospitalization for COVID-19 vs seasonal influenza. They used the health-care databases of the US Department of Veterans Affairs to analyze data from 92 265 hospitalized patients (mean age, 70.7 years; 74.2% White; 95.0% men). A total of 81 280 patients (mean age, 70.8 years) were hospitalized with COVID-19 infection between March 2020 and June 2022 and 10 985 patients (mean age, 70.5 years) were hospitalized for seasonal influenza between October 2015 and February 2019.

During 18 months of follow-up, the researchers evaluated and compared between the 2 groups the risk and burden of death, a prespecified set of 94 adverse health outcomes across 10 organ systems, overall burden across organ systems, hospital readmission, and admission to intensive care.

Inverse probability weighting was used to balance baseline characteristics between the 2 arms, according to the study.

FINDINGS

Results showed that over the 18 months of follow-up, the mortality rate was consistently higher among participants in the COVID-19 group. At 540 days, for example, the cumulative mortality rate per 100 persons was 28.46 (95% CI, 28.14-28.78) for participants in the COVID-19 group and 19.84 (95% CI, 19.07-20.59) for those in the influenza arm. Also, the excess death rate in the COVID-19 group vs the seasonal influenza group was 8.62 (95% CI, 7.55-9.44) per 100 persons.

In addition to the risk of mortality being higher among participants in the COVID-19 group for the duration of the study, researchers noted it was most apparent in the acute phase of infection (0-30 days following hospitalization; hazard ratio [HR] 2.51, 95% CI 2.28-2.78).

When investigators examined the comparative risks of 94 prespecified health outcomes across 10 organ systems, they found that patients in the COVID-19 group were more likely to experience 64 (68.1%) of the outcomes, including cardiovascular, hematologic, gastrointestinal, mental health, metabolic, musculoskeletal, neurologic, and kidney outcomes.

Compared to COVID-19, seasonal influenza was associated with an increased risk of 6 (6.4%) of the 94 health outcomes, including angina, tachycardia, type 1 diabetes, cough, hypoxemia, and shortness of breath.

In analyses of comparative risks by organ system, results showed that patients in the COVID-19 group were more likely to experience adverse outcomes in all organ systems except for the pulmonary system. The cumulative rate of adverse outcomes across all organ systems was 615.18 (95% CI, 605.17-624.88) per 100 persons for the COVID-19 arm and 536.90 (95% CI, 627.38-544.90) per 100 persons for the influenza group, corresponding to an excess rate of 78.72 (95% CI 66.15-91.24) per 100 persons for the COVID-19 group.

The total number of DALYs associated with adverse outcomes across all organ systems was higher among patients in the COVID-19 cohort (287.43 per 100 persons; 95% CI, 281.10-293.59) compared with those in the influenza cohort (242.66 per 100 persons; 95% CI, 236.75-247.67), according to the study.

“Decomposition analyses showed that in both COVID-19 and seasonal influenza, there was a higher burden of health loss in the post-acute than the acute phase; and comparatively, except for the pulmonary system, COVID-19 had a higher burden of health loss across all other organ systems than seasonal influenza in both the acute and post-acute phase,” added Xie and colleagues.

Compared to participants in the influenza group, those in the COVID-19 arm also had an increased risk of hospital readmission (HR, 1.11; 95% CI, 1.08-1.13) and a higher risk of admission to the intensive care unit (HR, 1.27; 95% CI, 1.19-1.36).

“The findings were consistent in analyses comparatively evaluating risks in seasonal influenza versus COVID-19 by individuals' respective vaccination status and in those admitted to hospital during the pre-delta, delta, and omicron eras,” added Xie et al.

They concluded: “Altogether, these findings emphasize the need to reduce the risk of infection and hospital admission due to SARS-CoV-2 and seasonal influenza and the need for post-acute care strategies to reduce the burden of health loss in populations.”

Source: Xie Y, Choi T, Al-Aly Z. Long-term outcomes following hospital admission for COVID-19 versus seasonal influenza: a cohort study. Lancet Infect Dis. Published online December 14, 2023. doi:10.1016/S1473-3099(23)00684-9