Predictors of Critical Illness During Different COVID-19 Pandemic Periods Compared With Seasonal Influenza

Since the onset of the COVID-19-pandemic, emerging virus variants, increasing population immunity, and evolving treatment strategies have substantially altered disease severity. This study aimed to identify predictors of critical illness due to COVID-19 over time and compare them with those of seasonal influenza in Sweden.

We conducted a retrospective, population-based cohort study using nationwide registry data. All individuals hospitalized for COVID-19 between 2020 and 2022 were categorized into five groups, based on pandemic waves and dominating virus variants. A sixth group included all patients hospitalized for influenza between 2018 and 2022. Patients were followed from hospitalization until ICU admission, in-hospital death, discharge, or end of study. Incidence rates were calculated and Cox regression identified predictors of ICU admission and in-hospital mortality, adjusting for age, sex, socioeconomic factors, comorbidities, and severe acute respiratory syndrome corona virus 2-vaccination. Data on influenza vaccinations were not available from the registers.

We included 92,428 COVID-19 hospitalizations and 21,355 influenza hospitalizations. Hospitalization rates were lowest during the delta-dominant period, while ICU admission rates were lowest during the Omicron-dominant period. The Omicron period most closely resembled influenza inpatient demographics, hospital stay duration, ICU admissions, and in-hospital mortality. Age distributions varied across pandemic periods, with the Omicron period showing an age profile similar to influenza (≈ 50% ≥ 75 yr). Adjusted hazard ratios for ICU-admission were strongest in unvaccinated patients, males, and individuals of 45-74 years for COVID-19, and in individuals of 45-64 years or with chronic lung diseases for influenza. Common predictors of in-hospital mortality included age older than 45 years (with a sharp increase after 74), male sex, and chronic comorbidities, and for COVID-19 also unvaccinated status.

Although COVID-19 consistently resulted in higher hospitalization rates than influenza, demographic and clinical patterns converged during the later pandemic stages. Advanced age was the strongest predictor of severe illness in both infections, with lack of vaccination additionally associated with severe COVID-19.