Long-term risk of post-acute sequelae among adults following SARS-CoV-2 or influenza virus infection: a retrospective cohort study in a large, integrated healthcare system

  1. Joseph A. Lewnard
  2. Debbie E. Malden
  3. Vennis Hong
  4. Jessica Skela
  5. Leora R. Feldstein
  6. Sharon Saydah
  7. Iris Anne C. Reyes
  8. Rulin Hechter
  9. Lina S. Sy
  10. Bradley K. Ackerson
  11. Sara Y. Tartof
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Abstract

Background

The comparative risk of post-acute sequelae (PAS) associated with SARS-CoV-2 and influenza virus infection remains unclear.

Methods

We undertook a retrospective cohort study within the Kaiser Permanente Southern California healthcare system of COVID-19 and influenza cases who received acute respiratory illness (ARI) diagnoses in virtual, outpatient, or inpatient settings between 1 September, 2022 and 31 December, 2023. We monitored PAS-associated healthcare utilization across all settings through 180 days after index ARI diagnoses. We estimated adjusted hazard ratios (aHRs) comparing COVID-19 cases to influenza cases, weighting to account for cases’ probability of retention in follow-up and infection with SARS-CoV-2 or influenza virus at the index ARI episode.

Results

Analyses included 74,738 COVID-19 cases and 18,790 influenza cases, among whom 35,835 (38.3%), 26,579 (28.4%), 23,388 (25.0%), and 7,726 (8.3%) received care for their index ARI episodes in virtual, ambulatory, emergency department, and inpatient settings, respectively. Risk of PAS diagnoses in any clinical setting was similar among COVID-19 and influenza cases (aHR=1.04 [95% confidence interval: 0.99-1.09] and aHR=1.01 [0.97-1.06] 31-90 and 91-180 days after index, respectively). However, COVID-19 cases experienced higher risk of severe PAS conditions necessitating inpatient care (aHR=1.31 [1.07-1.59] and aHR=1.24 [1.03-1.49] 31-90 and 91-180 days after index, respectively). This heightened risk of severe PAS following COVID-19 was concentrated among patients who required inpatient admission at their index episode.

Conclusions

PAS outcomes occur with similar frequency among non-severe COVID-19 cases and influenza cases. However, PAS among COVID-19 cases are more likely to require hospital admission than PAS among influenza cases.

Key points

  • Non-severe acute respiratory illnesses involving SARS-CoV-2 and influenza virus are associated with similar risk of post-acute sequelae (PAS).

  • Severe COVID-19 cases experience greater risk of PAS than severe influenza cases.

  • PAS following COVID-19 are more likely to necessitate hospital admission.

Article activity feed

  1. Version published to 10.1101/2025.05.30.25328674v1 on medRxiv