The Omicron variant of SARS CoV-2 is associated with milder symptoms and lower hospitalization and mortality rates than Delta variants,
although the impact of Omicron on immunocompromised patients, especially Solid Organ Transplant (SOT) recipients, is still unclear. This study compares the hospitalization rate and outcomes between immunocompromised, immunocompetent, and SOT patients during the Delta and Omicron periods. We included adult patients who tested positive for SARS-CoV-2 on PCR or nasopharyngeal antigen test between June 26, 2021 to September 8, 2022, at our institution. 12,401 COVID-19 patients were included, of which 11,055 were immunocompetent, and 1,346 were immuno-compromised (375 SOT recipients). Throughout the Delta and Omicron outbreaks, immunocompromised patients exhibited higher comorbidities and 30-day hospitalizations, but rates of mechanical ventilation and ICU-level care were like immunocompetent patients. During the Omicron wave, immunocompromised patients had higher unadjusted relative risk estimates (RR=2.37, 95% CI 1.96-2.87, p< 0.05) than Delta (RR=1.58, 95% CI 1.24-2.01, p< 0.05) with higher adjusted relative risk for hospitalization in Omicron (RR=1.50, 95% CI 1.10-2.03, p=0.01). Analyses show increased hospitalization risk in immunocompromised during the Omicron wave compared to the Delta wave with no significant difference in hospitalization outcomes. The relative risk of hospitalization for SOT patients was higher in both waves.