Disease severity of unvaccinated SARS-CoV-2 positive adults less than 65 years old without comorbidity, in the Omicron period and pre-Omicron periods

Background The reduced severity and burden of COVID-19 in 2022 can largely be attributable to vaccination and a shift to Omicron predominance. However, millions of individuals remain unvaccinated. In the present study, we aimed to study disease severity in unvaccinated individuals without risk factors during the Omicron period, compared to pre-Omicron periods. Methods This register-based study included all unvaccinated individuals in Sweden aged 18-64 years without comorbidity or care dependency who were SARS-CoV-2 positive between week 45 of 2020 and week 5 of 2022. Variant of concern (VOC) periods were periods with certain VOCs identified in ≥92% of sequenced cases nationwide. Outcomes were hospitalization with a main discharge code of COVID-19; severe illness, defined as high-flow nasal oxygen treatment or intensive care unit admission; and death with COVID-19 as the underlying cause of death on the death certificate. Results Among 788,895 individuals in the overall SARS-CoV-2 positive cohort, both hospitalization and death increased stepwise from the pre-VOC period to the Alpha and Delta periods, and decreased in the Omicron period. Among 15,179 patients hospitalized for COVID-19, the proportions with severe illness and death increased to the Delta period, but in the Omicron period, these outcomes returned to the level of the pre-VOC period. Conclusion In the Omicron period, compared to pre-Omicron periods, unvaccinated SARS-CoV-2 positive adults <65 years old without comorbidity had reduced proportions of hospitalization and death overall, but similar proportion of severe illness among patients hospitalized for COVID-19. These results support continuous efforts to prevent hospitalizations for COVID-19. ### Competing Interest Statement The authors have declared no competing interest. ### Funding Statement This study was funded by Swedens National Board of Health and Welfare ### Author Declarations I confirm all relevant ethical guidelines have been followed, and any necessary IRB and/or ethics committee approvals have been obtained. Yes The details of the IRB/oversight body that provided approval or exemption for the research described are given below: The study was approved by the Swedish Ethics Review Authority, Uppsala (Dnr 2020-04278). I confirm that all necessary patient/participant consent has been obtained and the appropriate institutional forms have been archived, and that any patient/participant/sample identifiers included were not known to anyone (e.g., hospital staff, patients or participants themselves) outside the research group so cannot be used to identify individuals. Yes I understand that all clinical trials and any other prospective interventional studies must be registered with an ICMJE-approved registry, such as ClinicalTrials.gov. I confirm that any such study reported in the manuscript has been registered and the trial registration ID is provided (note: if posting a prospective study registered retrospectively, please provide a statement in the trial ID field explaining why the study was not registered in advance). Yes I have followed all appropriate research reporting guidelines and uploaded the relevant EQUATOR Network research reporting checklist(s) and other pertinent material as supplementary files, if applicable. Yes The data underlying this article cannot be shared publicly due to regulations under Swedish law. According to the Swedish Ethics Review Act, the General Data Protection Regulation, and the Public Access to Information and Secrecy Act, patient data can only be made available, after legal review, to researchers who meet the criteria for access to this type of confidential data. Requests regarding data in this report may be made to the corresponding author.