The respiratory syndrome coronavirus (SARS-CoV-2) has undergone genetic evolution and led to variants of concern that vary in transmissibility and clinical severity.

This retrospective cohort analysis studied 232,364 hospitalized COVID-19-positive patients in the National COVID Cohort Collaborative [April 27, 2020 and June 25, 2022]. The primary outcomes were to compare demographics and need for mechanical ventilation and 30-day mortality across variants including Alpha (B.1.1.7), Delta (B.1.617.2), and Omicron (B.1.1.529).

The severity of SARS-CoV-2 decreased in the omicron-subsequent wave with decreased utilization of mechanical ventilation and decreased 30-day mortality among patients with comorbidities like diabetes mellitus, obesity, and liver disease. Although with each subsequent wave, the sex distribution remained equal and constant, there was an increase in rates of diabetes, liver disease, and respiratory disease amongst patients hospitalized with COVID-19 over the COVID waves despite the decreasing 30-day mortality and mechanical ventilation.

Despite changes in demographics over time, more recent COVID waves were associated with decreasing severity and mortality. These observations will help guide specific and effective resource allocation and patient care.