Higher in-hospital mortality in SARS-CoV-2 omicron variant infection compared to influenza infection—Insights from the CORONA Germany study

BACKGROUND: With the emergence of new subvariants, the disease severity of Severe Acute Respiratory Syndrome Coronavirus-2 has attenuated. This study aimed to compare the disease severity in patients hospitalized with omicron variant infection to those with influenza infection. METHODS: We compared data from the multicenter observational, prospective, epidemiological “CORONA Germany” (Clinical Outcome and Risk in hospitalized COVID-19 patients) study on patients infected with Severe Acute Respiratory Syndrome Coronavirus-2 to retrospective data on influenza infection cases from November 2016 to August 2022. Severe Acute Respiratory Syndrome Coronavirus-2 cases were classified as wild-type/delta variant before January 2022, or omicron variant from January 2022 onward. The primary outcome was in-hospital mortality, adjusted for age, gender, and comorbidities. RESULTS: The study included 35,806 patients from 53 hospitals in Germany, including 4,916 patients (13.7%) with influenza infection, 16,654 patients (46.5%) with wild-type/delta variant infection, and 14,236 patients (39.8%) with omicron variant infection. In-hospital mortality was highest in patients with wild-type/delta variant infection (16.8%), followed by patients with omicron variant infection (8.4%) and patients with influenza infection (4.7%). In the adjusted analysis, higher age was the strongest predictor for in-hospital mortality (age 80 years vs. age 50 years: OR 4.25, 95% CI 3.10–5.83). Both, patients with wild-type/delta variant infection (OR 3.54, 95% CI 3.02–4.15) and patients with omicron variant infection (OR 1.56, 95% CI 1.32–1.84) had a higher risk for in-hospital mortality than patients with influenza infection. CONCLUSION: After adjusting for age, gender and comorbidities, patients with wild-type/delta variant infection had the highest risk for in-hospital mortality compared to patients with influenza infection. Even for patients with omicron variant infection, the adjusted risk for in-hospital mortality was higher than for patients with influenza infection. The adjusted risk for in-hospital mortality showed a strong age dependency across all virus types and variants. TRIAL REGISTRATION NUMBER: NCT04659187.