Objective
This retrospective cohort study aims to assess the incidence and associated factors of in-hospital mortality and respiratory failure among patients with COVID-19 during the Omicron and Delta epidemics.

Methods
We reviewed medical records from a regional hospital in southern Thailand among COVID-19 patients during the Delta wave (August 2021 to December 2021) and the Omicron wave (February 2022 to June 2022). A computer-generated random sampling approach was employed to select patients for analysis. Logistic regression identified factors associated with respiratory failure, while Cox Proportional Hazard models were used for in-hospital mortality associations.

Findings
Among 5,729 hospitalized COVID-19 patients (Delta: 1,229; Omicron: 4,500), 1164 cases were randomly sampled (Delta: 295; Omicron: 869). Patients during the Delta wave were older (median: 52.0, interquartile range(IQR): 31.5-70.0) compared to Omicron (median: 37.0 IQR: 8.0-65.0), with lower completed two doses of vaccination rates (Delta: 18.3%; Omicron: 51.5%). Delta exhibited higher rates of respiratory failure (46.8% vs. Omicron: 22.3%) and in-hospital mortality (12.5% vs. Omicron: 6.9%). Increased age (adjusted odds ratio (aOR) 1.04, 95%CI:1.03-1.04), severity at admission (aOR 12.48, 95%CI:7.21-22.22), and delayed admission (aOR 1.07, 95%CI:1.02-1.12) increased respiratory failure risk, while received two-dose vaccination reduced this risk (aOR 0.36, 95%CI:0.24-0.53). Similarly, older age (adjusted hazard ratio(aHR) 1.05, 95%CI: 1.03-1.06), severity at admission (aHR 7.20, 95%CI:4.09-12.60), and delayed admission (aHR 1.05, 95%CI:1.00-1.11) were associated with higher in-hospital mortality, with two-dose vaccinations decreasing this risk (aHR 0.45, 95%CI:0.27-0.75).

Conclusion
Delta exhibited higher in-hospital mortality and respiratory failure rates compared to Omicron. Identified high-risk groups emphasize the critical need for timely care for vulnerable patients. The significance of timely access to care and vaccination coverage in reducing respiratory failure and mortality due to COVID-19 highlights the necessity for tailored interventions to mitigate the impact of emerging variants.