Comparative risk of post-acute sequelae among adults following SARS-CoV-2 or influenza virus infection, 2025, Tartof et al

rvallee

Senior Member (Voting Rights)
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

Background​

Post-acute sequelae (PAS) of SARS-CoV-2 infection are well documented. However, it remains unclear whether such long-term health effects are unique to COVID-19, or also occur following other viral respiratory infections.

Methods and findings​

We undertook a retrospective cohort study of 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, spanning virtual (n = 35,835; 38.3%), ambulatory (n = 26,579; 28.4%), emergency department (n = 23,388; 25.0%) and inpatient (n = 7,726; 8.3%) facilities. We compared 180-day risk of PAS-related healthcare utilization among COVID-19 cases and influenza via adjusted hazard ratios (aHRs) weighted to account for cases’ index infection type and follow-up retention. Adjustment models addressed patients’ demographic characteristics, comorbidity profiles, prior healthcare utilization patterns, and index episode severity. Risk of PAS diagnoses in any clinical setting was only modestly higher among COVID-19 cases in comparison to influenza cases within 31−90 days after cases’ initial illness (aHR = 1.04 [95% confidence interval: 0.99, 1.09]; risk difference = 0.6 [–0.1, 1.2] cases per 100 person-months). This difference was attenuated by 91−180 days (aHR = 1.01 [0.97, 1.06]; risk difference = 0.4 [–0.1, 0.9] cases per 100 person-months). However, 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). This excess risk of severe PAS was concentrated among COVID-19 cases hospitalized during acute-phase illness, and was attenuated among cases who received antiviral treatment, who had up-to-date vaccination status prior to infection, or who did not require inpatient admission for acute-phase illness. As a limitation, analyses included only PAS resulting in healthcare utilization; patient-reported symptoms and quality-of-life measures were not captured.

Conclusions​

In this large, real-world cohort, individuals with non-severe acute respiratory illness caused by SARS-CoV-2 experienced only modestly greater risk of 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. Our findings challenge assumptions about the uniqueness of post-acute COVID-19 morbidity and suggest the long-term burden of influenza may be underrecognized.

Author summary​

Why was this study done?​

  • It is known that people may suffer medical complications long after COVID-19, which are called post-acute sequelae (PAS).
  • Similar sequelae are also known to happen after people are infected with influenza or other respiratory viruses.
  • It is unclear whether PAS are a unique or more prominent feature of COVID-19 in comparison to influenza.

What did the researchers find?​

  • Risk of PAS was only modestly higher (4%) after COVID-19 in comparison to influenza.
  • By 91−180 days after infection, risk of PAS was similar for COVID-19 and influenza cases.
  • Differences in PAS risk were driven by the fact that people with severe COVID-19 tended to have greater risk of severe PAS afterwards.

What do these findings mean?​

  • PAS risk is similar among most COVID-19 and influenza cases, although people hospitalized for COVID-19 may be at particular risk.
  • While PAS is well understood to occur after COVID-19, the burden of PAS associated with influenza may have been historically overlooked.
  • As a key limitation of the study, outcomes encompass only PAS necessitating healthcare utilization. Patient-reported symptoms and quality-of-life measures are also important outcomes when measuring PAS.
 
A number of similar studies have been published in recent years, arguing the opposite conclusion, that Long Covid can be ignored because it's no worse than other infections illnesses, as long as one ignores that COVID is much more contagious.
Aside from influenza, PAS are also known to occur in association with numerous other respiratory viruses [69], including other sarbecoviruses [70], respiratory syncytial virus [71], enteroviruses [72], and Epstein–Barr virus [73]. Improved understanding of this post-acute burden can collectively inform the value of interventions aiming to prevent or mitigate the severity of respiratory virus infections.
Well, there is a huge decades-long record of millions of people saying so, begging the medical profession to do something about it. So far the answer has always been a simple: no, hell no, and always no.
 
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