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In patients hospitalized for either COVID-19 or seasonal influenza, rates of death, negative effects on long-term health, and hospital readmissions were high, but less so for the flu patients, a comparative analysis showed.

Over 18 months of follow-up, patients hospitalized with COVID had an increased risk of death compared with those hospitalized for influenza (HR 1.51, 95% CI 1.45-1.58), translating into an excess death rate of 8.62 per 100 persons, reported Ziyad Al-Aly, MD, of the VA St. Louis Health Care System and Washington University in St. Louis, and colleagues in .

In addition, COVID was associated with a significantly increased risk of 64 of 94 prespecified health outcomes, including cardiovascular outcomes, coagulation and hematological outcomes, fatigue, gastrointestinal outcomes, kidney outcomes, mental health outcomes, metabolic outcomes, musculoskeletal outcomes, neurological outcomes, and pulmonary outcomes.

Meanwhile, seasonal influenza was associated with increased risk of six outcomes compared with COVID: angina, tachycardia, type 1 diabetes, and three of four prespecified pulmonary outcomes (cough, hypoxemia, and shortness of breath).

The cumulative rates of adverse health outcomes across all organ systems were 615.18 per 100 persons in the COVID group and 536.90 per 100 persons in the influenza group, corresponding to an excess rate of 78.72 (95% CI 66.15-91.24) per 100 persons in the COVID group.

"Five years ago, it wouldn't have occurred to me to examine the possibility of a 'long flu,'" Al-Aly said in a . "A major lesson we learned from SARS-CoV-2 is that an infection that initially was thought to only cause brief illness also can lead to chronic disease."

Al-Aly and team also found that patients who had been hospitalized for COVID were at increased risks for hospital readmission and admission to the intensive care unit (ICU) during 18-month follow-up. In the COVID cohort, there were approximately 21 more hospital admissions (95% CI 16.10-24.86) and nine more ICU admissions (95% CI 6.68-11.82) per 100 persons compared with the influenza cohort.

The numbers of disability-adjusted life-years (DALYs) across all organ systems were 287.43 per 100 persons in the COVID group and 242.66 per 100 persons in the seasonal influenza group, translating to 45.03 (95% CI 37.15-52.90) higher DALYs per 100 persons in the COVID group.

"The main 'aha' moment for me was the realization that the toll of disease and disability is larger in the post-acute phase than the acute phase of illness," Al-Aly told MedPage Today. "This is true for both COVID and the flu."

Although both COVID and influenza pose potentially serious threats to long-term health, COVID remains a much more formidable threat, Al-Aly said. "COVID is really a multi-systemic disease, whereas, relatively speaking, flu is more respiratory," he noted. "We ought to take these illnesses seriously and do our best to make sure that people are protected through vaccination. Conceptualizing these illnesses as acute events -- as we often do -- ignores the much larger toll of disease and disability that emanates from the long phase of illness."

The study authors analyzed data from the healthcare databases of the U.S. Department of Veterans Affairs, and included 81,280 patients admitted to the hospital for COVID from March 1, 2020 to June 30, 2022 and 10,985 patients admitted for influenza from Oct. 1, 2015 to Feb. 28, 2019. Mean age was 71, 94.9% were men, and 73.9% were white.

Because the study evaluated risks of post-acute sequelae in people who required hospitalization for influenza or COVID, the results of the study cannot be extrapolated to those with milder infection, Al-Aly and team wrote. Moreover, the study population was comprised predominantly of older white men and may not represent the general population admitted to the hospital for influenza or COVID.

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