Protection From COVID-19 mRNA Vaccination and Prior SARS-CoV-2 Infection Against COVID-19–Associated Encounters in Adults During Delta and Omicron Predominance

Background. Data assessing protection conferred from COVID-19 mRNA vaccination and/or prior SARS-CoV-2 infection during Delta and Omicron predominance periods in the United States are limited. Methods. This cohort study included persons ≥18 years who had ≥1 health care encounter across 4 health systems and had been tested for SARS-CoV-2 before 26 August 2021. COVID-19 mRNA vaccination and prior SARS-CoV-2 infection defined the exposure. Cox regression estimated hazard ratios (HRs) for the Delta and Omicron periods; protection was calculated as (1−HR)×100%. Results. Compared to unvaccinated and previously uninfected persons, during Delta predominance, protection against COVID-19–associated hospitalizations was high for those 2- or 3-dose vaccinated and previously infected, 3-dose vaccinated alone, and prior infection alone (range, 91%–97%, with overlapping 95% confidence intervals [CIs]); during Omicron predominance, estimates were lower (range, 77%–90%). Protection against COVID-19–associated emergency department/urgent care (ED/UC) encounters during Delta predominance was high for those exposure groups (range, 86%–93%); during Omicron predominance, protection remained high for those 3-dose vaccinated with or without a prior infection (76%; 95% CI = 67%–83% and 71%; 95% CI = 67%–73%, respectively). Conclusions. COVID-19 mRNA vaccination and/or prior SARS-CoV-2 infection provided protection against COVID-19–associated hospitalizations and ED/UC encounters regardless of variant. Staying up-to-date with COVID-19 vaccination still provides protection against severe COVID-19 disease, regardless of prior infection.