Effectiveness of Messenger RNA-1273 Vaccine Booster Against Coronavirus Disease 2019 in Immunocompetent Adults

BACKGROUND: We conducted a prospective cohort study at Kaiser Permanente Southern California to evaluate the relative vaccine effectiveness (rVE) of a booster dose vs 2-dose primary series of messenger RNA (mRNA)-1273 in immunocompetent individuals. METHODS: Immunocompetent adults who received a booster dose of mRNA-1273 from October 2021 through December 2021 were matched 1:1 to randomly selected 2-dose mRNA-1273 recipients by age, sex, race/ethnicity, and second-dose date and followed up through January 2022. Cox proportional hazards models were used to estimate adjusted hazard ratios (aHRs) with 95% confidence intervals (CIs), comparing outcomes (severe acute respiratory syndrome coronavirus 2 [SARS-CoV-2] infection and coronavirus disease 2019 [COVID-19] hospitalization and hospital death) in the booster-dose and 2-dose groups. Adjusted rVE (%) was calculated as (1 − aHR) × 100. aHRs and rVE were also estimated by subgroup and month of follow-up. RESULTS: The study included 431 328 booster-dose vaccinated adults matched to 431 328 2-dose vaccinated adults. rVE was 61.3% (95% CI: 60.5%–62.2%) against SARS-CoV-2 infection, 89.0% (86.2%–91.2%) against COVID-19 hospitalization, and 96.0% (68.0%–99.5%) against COVID-19 hospital death. rVE against SARS-CoV-2 infection ranged from 55.6% to 66.7% across all subgroups. rVE against SARS-CoV-2 infection decreased from 67.1% (0 to <1 month of follow-up) to 30.5% (2 to <3 months). For COVID-19 hospitalization, rVE decreased from 91.2% (0 to <1 month) to 78.7% (2 to <3 months). CONCLUSIONS: Among immunocompetent adults, the mRNA-1273 booster conferred additional protection against SARS-CoV-2 infection and severe COVID-19 disease compared with the 2-dose mRNA-1273 primary series during periods of Delta and Omicron predominance.