Population-based comparison of post-acute sequelae of COVID-19 and health-related quality of life across pandemic periods: Omicron era versus early pandemic

Abstract

Abstract Post-COVID-19 syndrome (PCS) may vary across pandemic phases. We compared the prevalence of post-acute COVID-19 symptom clusters following SARS-CoV-2 infection in the early pandemic and during the Omicron era using a population-based approach. The EPILOC study enrolled individuals aged 18–65 years who tested PCR-positive for SARS-CoV-2 during the early pandemic, between October 2020 and April 2021, in defined geographic regions within Baden-Württemberg. EPILOC-Omicron used an identical design for individuals infected between June and July 2022. Participants completed a standardised questionnaire assessing sociodemographics, lifestyle, symptoms, and health-related quality of life (SF-12). PCS was defined as ≤ 80% recovery of general health or work capacity plus at least one new moderate-to-strong symptom, both compared to before index infection. Generalised linear models adjusted for age, sex, and education were used to estimate relative risks (RRs). We analysed data from 11,710 EPILOC (24% response) and 12,560 EPILOC-Omicron participants (17% response). Participants were similar in age and sex distribution. Vaccination before infection differed markedly (< 3 vs. > 92%). PCS prevalence was 29.6% in EPILOC and 14.5% in EPILOC-Omicron. Predictors of PCS were similar for both. Symptom clusters were consistently less frequent after infection during the Omicron era (e.g., fatigue RR = 0.54; neurocognitive impairment RR = 0.53; chest symptoms RR = 0.47; smell/taste disorder RR = 0.17). Health-related quality of life was similar in PCS cases of both cohorts (mean SF-12 Physical 40.3 vs. 41.0, mean SF-12 Mental 38.9 vs. 40.7). PCS was less common following SARS-CoV-2 infection in the Omicron era compared to the early pandemic period. However, affected individuals continue to experience substantial, comparable impairment in hrQoL across both pandemic periods.