Real-world effectiveness of the mRNA-1273 vaccine against COVID-19: Interim results from a prospective observational cohort study.

BACKGROUND: Phase 3 trials found mRNA-1273 was highly effective in preventing COVID-19. We conducted a prospective cohort study at Kaiser Permanente Southern California (KPSC) to determine the real-world vaccine effectiveness (VE) of mRNA-1273 in preventing COVID-19 infection and severe disease. METHODS: For this planned interim analysis, individuals aged ≥18 years receiving 2 doses of mRNA-1273 ≥24 days apart (18/12/2020-31/03/2021) were 1:1 matched to randomly selected unvaccinated individuals by age, sex, and race/ethnicity, with follow-up through 30/06/2021. Outcomes were COVID-19 infection (SARS-CoV-2 positive molecular test or COVID-19 diagnosis code) or severe disease (COVID-19 hospitalization and COVID-19 hospital death). Adjusted hazard ratios (aHR) and confidence intervals (CI) for COVID-19 outcomes comparing vaccinated and unvaccinated individuals were estimated by Cox proportional hazards models accounting for multiple comparisons. Adjusted VE was calculated as (1-aHR)x100. Whole genome sequencing was performed on SARS-CoV-2 positive specimens from the KPSC population. FINDINGS: This analysis included 352,878 recipients of 2 doses of mRNA-1273 matched to 352,878 unvaccinated individuals. VE (99·3% CI) against COVID-19 infection was 87·4% (84·8-89·6%). VE against COVID-19 hospitalization and hospital death was 95·8% (90·7-98·1%) and 97·9% (66·9-99·9%), respectively. VE was higher against symptomatic (88·3% [98·3% CI: 86·1-90·2%]) than asymptomatic COVID-19 (72·7% [53·4-84·0%]), but was generally similar across age, sex, and racial/ethnic subgroups. VE among individuals with history of COVID-19 ranged from 8·2-33·6%. The most prevalent variants were Alpha (41·6%), Epsilon (17·5%), Delta (11·5%), and Gamma (9·1%), with Delta increasing to 54·0% of variants by June 2021. INTERPRETATION: These interim results provide reassuring evidence of the VE of 2 doses of mRNA-1273 across age, sex, and racial/ethnic subgroups, and against asymptomatic and symptomatic COVID-19, and severe COVID-19 outcomes. Among individuals with history of COVID-19, mRNA-1273 vaccination may offer added protection beyond immunity acquired from prior infection. Longer follow-up is needed to fully evaluate VE of mRNA-1273 against emerging SARS-CoV-2 variants. FUNDING: Moderna Inc.