Serious hospital events following symptomatic infection with Sars-CoV-2 Omicron and Delta variants: an exposed-unexposed cohort study in December 2021 from the COVID-19 surveillance databases in France

Background: A rapid increase in incidence of the SARS-CoV-2 Omicron variant in France in December 2021, while the Delta variant was prevailing since July 2021. Aim: To determine whether the risk of occurrence of a serious hospital event in adults following symptomatic SARS-CoV-2 infection differs for Omicron versus Delta. Methods: A retrospective cohort study from 06/12/2021 to 07/01/2022. The outcome was a serious hospital event (admission to intensive care unit OR admission to critical care unit OR death). Omicron and Delta symptomatic cases were matched on the week of virological diagnosis and on age. Risk was adjusted for age, sex, vaccination status, presence of comorbidity and region of residence using Cox proportional-hazards model. Results: 149,064 cases were included of which 497 had a serious hospital event (447 in the Delta arm, 50 in the Omicron arm). The risk of serious event was lower among Omicron versus Delta cases (adjusted Hazard Ratio, aHR=0.13 CI95 0.09-0.18 in 18 to 79 yo, aHR=0.30 CI95 0.17-0.54 in 80+ yo). The risk increased sharply with age and was lower in vaccinated compared to unvaccinated, without interaction between variant and vaccination status (aHR=0.15 CI95 0.11-0.19 for 18-79 yo with primary vaccination versus unvaccinated), was higher in cases with comorbidities (aHR = 3.70 CI95 2.66-5.13 fort 18-79 yo with very-high-risk comorbidity versus no comorbidity) and in males. Conclusion: This study confirms the lower severity of Omicron. The vaccine protection is essential in the elderly as they have a high risk of severe hospital events following infection with Omicron, even if much this risk is lower than with Delta.