Publication date: Nov 04, 2024

Background: Understanding protection against SARS-CoV-2 infection by vaccine and hybrid immunity is important for informing public health strategies as new variants emerge. Methods: We analyzed data from three cohort studies spanning September 1, 2022-July 31, 2023, to estimate COVID-19 vaccine effectiveness (VE) against SARS-CoV-2 infection and symptomatic COVID-19 among adults with and without prior infection in the United States. Participants collected weekly nasal swabs, irrespective of symptoms, annual blood draws, and completed periodic surveys, which included vaccination status and prior infection history. Swabs were tested molecularly for SARS-CoV-2. VE was estimated using Cox proportional hazards models for the hazard ratios of infections, adjusting for covariates. VE was calculated considering prior infection and recency of vaccination. Results: Among 3,343 adults, adjusted VE of bivalent vaccine against infection was 37.2% (95% CI: 11.4-58.5%) within 7-60 days of vaccination and 17.0% (95% CI: -3.7-33.2%) within 60-179 days of vaccination compared to participants who were unvaccinated/received an original monovalent vaccine dose at least 180 days prior. Overall, adjusted VE of bivalent vaccine, in conjunction with prior infection, was 62.2% (95% CI: 44.2-74.6%) within 7-179 days of vaccination and 39.4% (95% CI: 11.7-61.3%) at least 180 days ago compared to naive participants who were unvaccinated/received a monovalent vaccine dose at least 180 days prior. Conclusions: Adults with both prior infection and recent vaccination had high protection against infection and symptomatic illness. Recent vaccination alone provided moderate protection.

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