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COVID-19

COVID-19 Long-Term Health Effects May Be Underrecognized

Strategic Insights

— 2 min read

A new study published in PLOS Medicine has revealed that individuals with non-severe acute respiratory illness caused by SARS-CoV-2 experienced only modestly greater risk of post-acute sequelae (PAS) in comparison to those whose illness was caused by influenza. However, COVID-19 cases hospitalized for their initial illness experienced greater risk of severe PAS necessitating inpatient care, and this difference persisted through 180 days of follow-up.

Key Takeaways:

  • The study analyzed 74,738 COVID-19 cases and 18,790 influenza cases within the Kaiser Permanente Southern California healthcare system diagnosed between 1 September, 2022 and 31 December, 2023.
  • Cases received care for index infections across a spectrum of clinical settings, with 35,835 (38.3%) receiving virtual care, 26,579 (28.4%) ambulatory care, 23,388 (25.0%) emergency department care, and 7,726 (8.3%) inpatient care.
  • The risk of PAS diagnoses in any clinical setting was only modestly higher among COVID-19 cases compared to influenza cases within 31-90 days after initial illness (1.04 [95% confidence interval: 0.99, 1.09]; risk difference = 0.6 [-0.1, 1.2] cases per 100 person-months).
  • COVID-19 cases faced higher risk of severe PAS conditions requiring hospitalization (aHR = 1.31 [1.07, 1.59] and 1.24 [1.03, 1.49] within 31-90 and 91-180 days, respectively).
  • The excess risk of severe PAS was concentrated among COVID-19 cases hospitalized during acute-phase illness, and was attenuated among cases receiving antiviral treatment, having up-to-date vaccination status prior to infection, or not requiring inpatient admission for acute-phase illness.
  • The study concluded that the long-term burden of influenza may be underrecognized and challenged assumptions about the uniqueness of post-acute COVID-19 morbidity.

Statistics:

  • 74,738 COVID-19 cases and 18,790 influenza cases were analyzed in the study.
  • 35,835 (38.3%) COVID-19 cases received virtual care, 26,579 (28.4%) ambulatory care, 23,388 (25.0%) emergency department care, and 7,726 (8.3%) inpatient care.
  • The risk difference between COVID-19 and influenza cases was 0.6 [-0.1, 1.2] cases per 100 person-months within 31-90 days.
  • The risk difference between COVID-19 and influenza cases was 0.4 [-0.1, 0.9] cases per 100 person-months within 91-180 days.
  • COVID-19 cases faced 1.31 [1.07, 1.59] and 1.24 [1.03, 1.49] times higher risk of severe PAS conditions requiring hospitalization within 31-90 and 91-180 days, respectively.

Sources:

  • NewsRx. Findings from Debbie E. Malden and Co-Authors in the Area of COVID-19 Reported (Comparative risk of post-acute sequelae among adults following SARS-CoV-2 or influenza virus infection: A retrospective cohort study among United States adults). Clinical Trials Week. October 20, 2025; p 34.
  • Comparative risk of post-acute sequelae among adults following SARS-CoV-2 or influenza virus infection: A retrospective cohort study among United States adults. PLOS Medicine, 2025;22(10).
  • Public Library Science. PLOS Medicine. www.plosmedicine.org
  • Debbie E. Malden, Kaiser Permanente Southern California Dept. of Research & Evaluation, Pasadena, California, United States.

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