Clinical Outcomes in Patients Hospitalized for COVID-19 in the Periods of Non-Omicron and Omicron Variant Dominance

Background Omicron is known for its higher transmissibility and milder respiratory symptoms than those of other SARS-CoV-2 variants. How comorbidities contribute to mortality outcomes in Omicron-related COVID-19 remains unclear. This study compared clinical features and outcomes between Omicron and non-Omicron variants and identified risk factors for in-hospital mortality. Methods This retrospective cohort study was conducted from April 2020 to September 2022. Patients with COVID-19 infection were divided into Omicron and non-Omicron groups. Demographic data, laboratory results, and treatment information were collected and analyzed. Clinical outcomes for different variants were analyzed. Results The Omicron group had a greater burden of comorbidities but exhibited lower COVID-19 disease severity and fewer complications than did the non-Omicron group. Overall mortality was relatively high in the Omicron group, primarily due to non-COVID-related causes. In multivariate analysis, a Charlson comorbidity index score of ≥3 (odds ratio [OR] = 4.60, 95% confidence interval [CI] = 1.94–10.91, p < 0.001), severe or critical COVID-19 (OR = 1.60, 95% CI = 1.24–2.07, p < 0.001), a high white blood cell count (OR = 1.00, 95% CI = 1.00–1.00, p = 0.021), and a high C-reactive protein level (OR = 1.01, 95% CI = 1.00–1.01, p = 0.003) emerged as positive predictors of COVID-19-related mortality. Conclusion Severe or critical COVID-19 and a Charlson comorbidity index score of ≥3 were independently associated with high in-hospital mortality. Intensive monitoring and early intervention should be prioritized for high-risk groups to improve clinical outcomes.