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Introduction: There is accumulating evidence that Post-COVID-19 Syndrome (PCS) is more prevalent in individuals who were infected with early variants of SARS-CoV-2 compared to later ones. We aimed to compare the prevalence of post-acute COVID-19 symptom clusters following Omicron versus wild-type infection using a population-based approach.

Methods: EPILOC is a population-based study conducted in Baden-Württemberg, including subjects aged 18 to 65 years who tested PCR-positive for SARS-CoV-2 (mainly wild-type) between 1 Oct. 2020 and 1 Apr. 2021. EPILOC-Omicron applied an identical study design covering the same target region and included subjects with confirmed SARS-CoV-2 infection (PCR or POC-AGT-positive) between 15 June 2022 and 15 July 2022. Subjects from both cohorts completed a standardised questionnaire, which was largely identical, covering sociodemographic characteristics, lifestyle factors, health-related quality of life (as measured by the SF-12), and the presence of specific symptoms. PCS was defined as “general health or working capacity recovered to a level of no more than 80% (compared to pre-COVID-19), and any new symptom (not present before infection) of moderate to strong intensity”. Generalised linear models were used to derive relative risks with 95% confidence intervals adjusted for age-class-sex combinations and education.

Results: Data of 11,710 EPILOC (24% response) and 12,560 EPILOC-Omicron participants (17% response) could be analysed; mean age (44.1 vs. 45.9 years) and sex (58.8% vs. 62.4% female) were similar in both cohorts. Mean time since infection was 8.5 months for EPILOC and 14.7 months for EPILOC-Omicron. Less than 2% of EPILOC had been vaccinated before infection vs. more than 92% of EPILOC-Omicron. Overall, 29.6% of EPILOC and 14.5% of EPILOC-Omicron fulfilled the EPILOC PCS case definition. Predictors of PCS were the same for both cohorts (i.e. older age, female sex, lower education, smoking, obesity, treatment of the acute infection, and pre-existing medical conditions). However, all symptom clusters were less prevalent after Omicron vs. wild-type infection, e.g., fatigue 12.3% vs. 23.1%, RR=0.54 (95%-CI 0.51 to 0.57); neurocognitive impairment 8.1% vs. 15.3%, RR=0.53 (95%-CI 0.50 to 0.58); chest symptoms 6.4% vs. 14.2%, RR=0.47 (95%-CI 0.43 to 0.51); smell or taste disorder 2.0% vs 11.8%, RR=0.17 (95%-CI 0.15 to 0.20). Health-related quality of life was similarly in PCS cases of both cohorts (median SF-12Physical 40.3 vs. 41.0, median SF-12Mental 38.9 vs. 40.7).

Conclusion: Although PCS is less prevalent after infection with the Omicron variant, affected individuals continue to experience substantial and comparably impaired health-related quality of life, regardless of the variant.

The author declares that he has no competing interests.

The author declares that a positive ethics committee vote has been obtained.