Introduction : We aimed to compare the severity of the Delta variant and the Omicron sub-lineages BA.1, BA.2 and BA.4/5 in patients hospitalized directly because of COVID-19 at the largest university hospital in Switzerland.

Methods : We conducted a retrospective monocentre cohort study including patients recorded in the COVID-19 Hospital Based Surveillance system hospitalized because of a Delta or different Omicron sub-lineages infection from July 1, 2021 to September 28, 2022. Multinomial regression models with propensity score weighting to balance for confounding were used to assess the clinical severity of each variant. Additional time-to-event analyses were performed using Kaplan-Meier methodology.

Results : The minimum number of eligible patients before variable imputation amounted to 1,475 (320, 340, 164 and 299 infected by Delta, Omicron BA.1, BA.2 and BA.4/5 respectively). Over time, the hospitalized populations became older and more frequently vaccinated (p < 0.001). No statistical significance was observed in the clinical severity among the three Omicron sub-lineages. In comparison to being infected with Delta, being infected with all tested Omicron lineages was associated with a decreased probability of severe or critical disease. The odds ratios for severe or critical disease, respectively, were as follows: (OR 0.33 (95 % CI 0.13; 0.83, p = 0.005) and 0.27 (95 % CI 0.10; 0.75, p < 0.001) for Omicron BA.1); (0.37 (95 % CI 0.14; 0.97, p = 0.020) and 0.23 (95 % CI 0.08; 0.70, p < 0.001) for Omicron BA.2); and (0.33 (95 % CI 0.13; 0.83, p = 0.005) and 0.12 (95 % CI 0.03; 0.41, p < 0.001) for Omicron BA.4/5).

Discussion : Our study confirmed the decreased severity of Omicron in hospitalized patients and highlights the burden of COVID-19 for older adults who require hospitalization even when presenting with mild disease, mainly because of a decompensation of an underlying disease.