Background
Respiratory viral infections have significant global health impacts. We compared 30-day intensive care unit (ICU) admission and all-cause mortality risks in patients with severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) Delta and Omicron variants versus influenza A and B (A/B).

Methods
Data from two retrospective inpatient cohorts in Copenhagen were analyzed. Cohorts included hospitalized influenza A/B patients (2017–2018) and SARS-CoV-2 Delta/Omicron patients (2021–2022), aged ≥18 years, admitted within 14 days of a positive real-time polymerase chain reaction test result. Cumulative ICU admission and mortality rates were estimated using the Aalen–Johansen estimator. Cox regression models calculated hazard ratios (HRs) for ICU admission and mortality.

Results
The study encompassed 1459 inpatients (Delta: 49%; Omicron: 26%; influenza A: 6.4%; and influenza B: 18%). Cumulative incidence of ICU admission was 11%, 4.0%, 7.5%, and 4.1%, for Delta, Omicron, influenza A, and B, respectively. For ICU admission, adjusted HRs (aHRs) were 3.1 (p < .001) and 1.5 (p = .34) for Delta and Omicron versus influenza B, and 1.5 (p = .36) and 0.71 (p = .48) versus influenza A. For mortality, aHRs were 3.8 (p < .001) and 3.4 (p < .001) for Delta and Omicron versus influenza B, and 2.1 (p = .04) and 1.9 (p = .11) versus influenza A.

Conclusion
Delta but not Omicron inpatients had an increased risk for ICU admission compared to influenza B; however, both variants were associated with higher risks of mortality than influenza B. Only Delta inpatients had a higher risk of mortality than influenza A inpatients.