Background

The Omicron SARS-CoV-2 variant is rapidly spreading in the US since December 2021 and is more contagious than earlier variants. Currently, data on the severity of the disease caused by the Omicron variant compared with the Delta variant is limited. Here we compared 3-day risks of emergency department (ED) visit, hospitalization, intensive care unit (ICU) admission, and mechanical ventilation in patients who were first infected during a time period when the Omicron variant was emerging to those in patients who were first infected when the Delta variant was predominant.

Method

This is a retrospective cohort study of electronic health record (EHR) data of 577,938 first-time SARS-CoV-2 infected patients from a multicenter, nationwide database in the US during 9/1/2021–12/24/2021, including 14,054 who had their first infection during the 12/15/2021–12/24/2021 period when the Omicron variant emerged (“Emergent Omicron cohort”) and 563,884 who had their first infection during the 9/1/2021–12/15/2021 period when the Delta variant was predominant (“Delta cohort”). After propensity-score matching the cohorts, the 3-day risks of four outcomes (ED visit, hospitalization, ICU admission, and mechanical ventilation) were compared. Risk ratios, and 95% confidence intervals (CI) were calculated.

Results

Of 14,054 patients in the Emergent Omicron cohort (average age, 36.4±24.3 years), 27.7% were pediatric patients (< 18 years old), 55.4% female, 1.8% Asian, 17.1% Black, 4.8% Hispanic, and 57.3% White. The Emergent Omicron cohort differed significantly from the Delta cohort in demographics, comorbidities, and socio-economic determinants of health. After propensity-score matching for demographics, socio-economic determinants of health, comorbidities, medications and vaccination status, the 3-day risks in the Emergent Omicron cohort outcomes were consistently less than half those in the Delta cohort: ED visit: 4.55% vs. 15.22%(risk ratio or RR: 0.30, 95% CI: 0.28–0.33); hospitalization: 1.75% vs. 3.95%(RR: 0.44, 95% CI: 0.38–0.52]); ICU admission: 0.26% vs. 0.78%(RR: 0.33, 95% CI: 0.23–0.48); mechanical ventilation: 0.07% vs. 0.43%(RR: 0.16, 95% CI: 0.08–0.32). In children under 5 years old, the overall risks of ED visits and hospitalization in the Emergent Omicron cohort were 3.89% and 0.96% respectively, significantly lower than 21.01% and 2.65% in the matched Delta cohort (RR for ED visit: 0.19, 95% CI: 0.14–0.25; RR for hospitalization: 0.36, 95% CI: 0.19–0.68). Similar trends were observed for other pediatric age groups (5–11, 12–17 years), adults (18–64 years) and older adults (≥ 65 years).

Conclusions

First time SARS-CoV-2 infections occurring at a time when the Omicron variant was rapidly spreading were associated with significantly less severe outcomes than first-time infections when the Delta variant predominated.