Effectiveness of Messenger RNA–based Vaccines During the Emergence of the Severe Acute Respiratory Syndrome Coronavirus 2 Omicron Variant

Background We evaluated effectiveness of mRNA-based vaccines following emergence of SARS-CoV-2 Omicron variant. Methods Recipients of a third dose of BNT162b2 or mRNA-1273 ≥ 180 days after the primary series were matched to primary series recipients and unvaccinated persons. Participants were followed from December 1, 2021 to March 12, 2022. Outcomes were documented SARS-CoV-2 infection, COVID-19 hospitalization, and COVID-19 death. Effectiveness was calculated from 100-day risks estimated with the Kaplan-Meier estimator. Results BNT162b2 and mRNA-1273 groups respectively included 221,267 and 187,507 third dose recipients matched to equal numbers of primary series recipients and unvaccinated persons. Compared to no vaccination, effectiveness of a third dose of BNT162b2 was 47.8% (95% confidence interval [CI]: 45.2-50.3), 81.8% (95% CI 79.2-84.2), and 89.6% (95% CI 85.0-93.6) against documented infection, hospitalization, and death, respectively. Effectiveness of a third dose of BNT162b2 compared to the primary series was 30.1% (95% CI 26.2-33.7), 61.4% (95% CI 55.0-67.1), and 78.8% (95% CI 67.9-87.5) against documented infection, hospitalization, and death, respectively. Effectiveness of a third dose of mRNA-1273 compared to no vaccination was 61.9% (95% CI 59.4-64.4), 87.9% (95% CI 85.3-90.2), and 91.4% (95% CI 86.4-95.6) against documented infection, hospitalization, and death, respectively. Effectiveness of a third dose of mRNA-1273 compared to the primary series was 37.1% (95% CI 32.2-41.7), 63.5% (95% CI 53.7-71.6), and 75.0% (95% CI 55.4-88.0) against documented infection, hospitalization, and death, respectively. Conclusions BNT162b2 and mRNA-1273 were effective against COVID-19 following emergence of Omicron variant. A third dose provided additional protection over the primary series.