Reduced Risk of Hospitalisation Associated With Infection With SARS-CoV-2 Omicron Relative to Delta: A Danish Cohort Study

Background: Estimates of the severity of the emerging Omicron variant (lineage B.1.1.529) are critical to assess the public health impact associated with its rapid global dissemination. We estimated the risk of SARS-CoV-2-related hospitalizations after infection with Omicron compared to Delta overall and stratified by vaccination status in Denmark, a country with high mRNA vaccination coverage and an extensive free-of-charge PCR test capacity.Methods: Observational cohort study of all RT-PCR SARS-CoV-2 positive individuals in Denmark between 21 November and 19 December, 2021, the period Omicron emerged while Delta was still the dominant variant. Individuals including hospitalised cases, were identified in the national COVID-19 surveillance system database including results of a variant specific RT-PCR detecting Omicron cases (vPCR), the National Patient Registry, the National Vaccination Registry, as well as other nationwide registers. The risk ratio (RR) of admission for Omicron compared to Delta infection, overall and stratified by vaccination status, was calculated in a Poisson regression model with robust standard errors, adjusted à priori for reinfection status, sex, age, region, comorbidities, and calendar week of sampling.Findings: Among the 188,980 SARS-CoV-2 infected individuals, 38,669 (20.1%) were Omicron vPCR positive. SARS-CoV-2 related hospitalisations and Omicron cases increased during the study period. Overall, 65.8 % were vaccinated and vaccination was associated with a lower risk of hospitalisation (adjusted RR 0.25, 95%CI 0.22-0.27), compared to cases with no or one vaccination. Compared to Delta infection, Omicron was associated with an adjusted RR of hospitalisation of 0.64 (95%CI 0.56-0.75). The RR of hospitalisation was 0.57 (95%CI 0.44-0.75) among cases with no or one vaccination, 0.71 (95%CI 0.60-0.86) among two-dose vaccinated, and 0.50 (95%CI 0.32-0.76) among three-dose vaccinated.Interpretation: We found a significantly lower risk of hospitalisation with Omicron infection compared to Delta among both vaccinated and unvaccinated individuals suggesting an inherent reduced severity of Omicron. Our results can guide modelling of the impact of the rapid spread of Omicron globally and thus health care system preparedness.Funding Information: The authors received no specific funding for this work. Declaration of Interests: We declare no competing interest.Ethics Approval Statement: All analyses were based on information from the national COVID-19 surveillance system database updated and extracted on 4 January, 2022. This study was done with use of administrative register data. According to Danish law, ethics approval is not needed for such research.