Abstract
OBJECTIVE: This study reports the vaccine effectiveness (VE) of COVID-19 vaccine regimens in the United States, based on the National COVID Cohort Collaborative (N3C) database. METHODS: Data from 10.4 million adults, enrolled in the N3C from 11 December 2020 to 30 June 2022, were analyzed. VE against infection and death outcomes were evaluated across 13 vaccine regimens in recipient cohorts during the Pre-Delta, Delta, and Omicron periods. VE was estimated as (1-odds ratio) × 100% by multivariate logistic regression, using the unvaccinated cohort as reference. RESULTS: Natural immunity showed a highly protective effect (70.33%) against re-infection, but the mortality risk among the unvaccinated population was increased after re-infection; vaccination following infection reduced the risk of re-infection and death. mRNA-1273 full vaccination plus mRNA-1273 booster showed the highest anti-infection effectiveness (47.59%) (95% CI, 46.72-48.45) in the overall cohort. In the type 2 diabetes cohort, VE against infection was highest with BNT162b2 full vaccination plus mRNA-1273 booster (61.19%) (95% CI, 53.73-67.75). VE against death was also highest with BNT162b2 full vaccination plus mRNA-1273 booster (89.56%) (95% CI, 85.75-92.61). During the Pre-Delta period, all vaccination regimens showed an anti-infection effect; during the Delta period, only boosters, mixed vaccines, and Ad26.COV2.S vaccination exhibited an anti-infection effect; during the Omicron period, none of the vaccine regimens demonstrated an anti-infection effect. Irrespective of the variant period, even a single dose of mRNA vaccine offered protection against death, thus demonstrating survival benefit, even in the presence of infection or re-infection. Similar patterns were observed in patients with type 2 diabetes. CONCLUSIONS: Although the anti-infection effect declined as SARS-CoV-2 variants evolved, all COVID-19 mRNA vaccines had sustained effectiveness against death. Vaccination was crucial for preventing re-infection and reducing the risk of death following SARS-CoV-2 infection.