• Dan-Yu Lin, Yu Gu, Yangjianchen Xu, Bradford Wheeler, Hayley Young, Shadia Khan Sunny, Zack Moore, and Donglin Zeng.
• Gillings School of Global Public Health, University of North Carolina at Chapel Hill, Chapel Hill.
• JAMA. 2022 Oct 11; 328 (14): 141514261415-1426.

ImportanceData about the association of COVID-19 vaccination and prior SARS-CoV-2 infection with risk of SARS-CoV-2 infection and severe COVID-19 outcomes may guide prevention strategies.ObjectiveTo estimate the time-varying association of primary and booster COVID-19 vaccination and prior SARS-CoV-2 infection with subsequent SARS-CoV-2 infection, hospitalization, and death.Design, Setting, And ParticipantsCohort study of 10.6 million residents in North Carolina from March 2, 2020, through June 3, 2022.ExposuresCOVID-19 primary vaccine series and boosters and prior SARS-CoV-2 infection.Main Outcomes And MeasuresRate ratio (RR) of SARS-CoV-2 infection and hazard ratio (HR) of COVID-19-related hospitalization and death.ResultsThe median age among the 10.6 million participants was 39 years; 51.3% were female, 71.5% were White, and 9.9% were Hispanic. As of June 3, 2022, 67% of participants had been vaccinated. There were 2 771 364 SARS-CoV-2 infections, with a hospitalization rate of 6.3% and mortality rate of 1.4%. The adjusted RR of the primary vaccine series compared with being unvaccinated against infection became 0.53 (95% CI, 0.52-0.53) for BNT162b2, 0.52 (95% CI, 0.51-0.53) for mRNA-1273, and 0.51 (95% CI, 0.50-0.53) for Ad26.COV2.S 10 months after the first dose, but the adjusted HR for hospitalization remained at 0.29 (95% CI, 0.24-0.35) for BNT162b2, 0.27 (95% CI, 0.23-0.32) for mRNA-1273, and 0.35 (95% CI, 0.29-0.42) for Ad26.COV2.S and the adjusted HR of death remained at 0.23 (95% CI, 0.17-0.29) for BNT162b2, 0.15 (95% CI, 0.11-0.20) for mRNA-1273, and 0.24 (95% CI, 0.19-0.31) for Ad26.COV2.S. For the BNT162b2 primary series, boosting in December 2021 with BNT162b2 had the adjusted RR relative to primary series of 0.39 (95% CI, 0.38-0.40) and boosting with mRNA-1273 had the adjusted RR of 0.32 (95% CI, 0.30-0.34) against infection after 1 month and boosting with BNT162b2 had the adjusted RR of 0.84 (95% CI, 0.82-0.86) and boosting with mRNA-1273 had the adjusted RR of 0.60 (95% CI, 0.57-0.62) after 3 months. Among all participants, the adjusted RR of Omicron infection compared with no prior infection was estimated at 0.23 (95% CI, 0.22-0.24) against infection, and the adjusted HRs were 0.10 (95% CI, 0.07-0.14) against hospitalization and 0.11 (95% CI, 0.08-0.15) against death after 4 months.Conclusions And RelevanceReceipt of primary COVID-19 vaccine series compared with being unvaccinated, receipt of boosters compared with primary vaccination, and prior infection compared with no prior infection were all significantly associated with lower risk of SARS-CoV-2 infection (including Omicron) and resulting hospitalization and death. The associated protection waned over time, especially against infection.

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