Prior observation has shown differences in COVID-19 hospitalization risk between SARS-CoV-2 variants, but limited information describes hospitalization outcomes.
Inpatients with COVID-19 at five hospitals in the eastern United States were included if they had hypoxia, tachypnea, tachycardia, or fever, and SARS-CoV-2 variant data, determined from whole genome sequencing or local surveillance inference. Analyses were stratified by history of SARS-CoV-2 vaccination or infection. The average effect of SARS-CoV-2 variant on 28-day risk of severe disease, defined by advanced respiratory support needs, or death was evaluated using models weighted on propensity scores derived from baseline clinical features.
Severe disease or death within 28 days occurred for 977 (29%) of 3,369 unvaccinated patients and 269 (22%) of 1,230 patients with history of vaccination or prior SARS-CoV-2 infection. Among unvaccinated patients, the relative risk of severe disease or death for Delta variant compared to ancestral lineages was 1.30 (95% confidence interval [CI] 1.11-1.49). Compared to Delta, this risk for Omicron patients was 0.72 (95% CI 0.59-0.88) and compared to ancestral lineages was 0.94 (95% CI 0.78-1.1). Among Omicron and Delta infections, patients with history of vaccination or prior SARS-CoV-2 infection had half the risk of severe disease or death (adjusted hazard ratio 0.40, 95% CI 0.30-0.54), but no significant outcome difference by variant.
Although risk of severe disease or death for unvaccinated inpatients with Omicron was lower than Delta, it was similar to ancestral lineages. Severe outcomes were less common in vaccinated inpatients, with no difference between Delta and Omicron infections.

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