Question
How does the association of COVID-19 vaccination and prior SARS-CoV-2 infection with subsequent SARS-CoV-2 infection and severe COVID-19 outcomes change over time?
Findings
In a cohort study of 10.6 million North Carolina residents from March 2020 to June 2022, receipt of a primary COVID-19 vaccine series compared with being unvaccinated, receipt of a booster compared with primary vaccination, and prior SARS-CoV-2 infection compared with no prior infection were all significantly associated with lower risk of SARS-CoV-2 infection and resulting hospitalization and death. The estimates for the associated protection decreased over time, especially for the outcome of infection, and varied by type of circulating variant.
Meaning
Receipt of COVID-19 vaccines and boosters, as well as prior SARS-CoV-2 infection, were associated with protection against SARS-CoV-2 infection (including Omicron) and severe COVID-19 outcomes, although the associated protection waned over time.
Importance
Data 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.
Objective
To 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 Participants
Cohort study of 10.6 million residents in North Carolina from March 2, 2020, through June 3, 2022.
Exposures
COVID-19 primary vaccine series and boosters and prior SARS-CoV-2 infection.
Main Outcomes and Measures
Rate ratio (RR) of SARS-CoV-2 infection and hazard ratio (HR) of COVID-19–related hospitalization and death.
Results
The 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 Relevance
Receipt 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.