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?
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.
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.
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.
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.
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.
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.
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CME Disclosure Statement: Unless noted, all individuals in control of content reported no relevant financial relationships. If applicable, all relevant financial relationships have been mitigated.
Corresponding Author: Dan-Yu Lin, PhD, Department of Biostatistics, 3101E McGavran-Greenberg Hall, University of North Carolina at Chapel Hill, Chapel Hill, NC 27599-7420 (firstname.lastname@example.org).
Accepted for Publication: September 13, 2022.
Published Online: September 26, 2022. doi:10.1001/jama.2022.17876
Author Contributions: Dr Lin had full access to all the data in the study and takes responsibility for the integrity of the data and the accuracy of the data analysis.
Concept and design: Lin
Acquisition, analysis, or interpretation of data: All authors.
Drafting of the manuscript: Lin.
Critical revision of the manuscript for important intellectual content: All authors.
Statistical analysis: Gu, Xu.
Obtained funding: Lin, Zeng.
Supervision: Lin, Zeng.
Conflict of Interest Disclosures: None reported.
Funding/Support: This research was supported by the Dennis Gillings Distinguished Professorship (Dr Lin) and the National Institutes of Health R01 grants (Dr Lin, Ms Gu, Mr Xu, and Dr Zeng).
Role of the Funder/Sponsor: The funders had no role in the design and conduct of the study; collection, management, analysis, and interpretation of the data; preparation, review, or approval of the manuscript; and decision to submit the manuscript for publication.
Additional Contributions: The authors thank the individuals involved in the COVID-19 response at the state and local health departments in North Carolina for generating the surveillance data. They would also like to thank Aaron Fleischauer, MD, from North Carolina Department of Health and Human Services for facilitating this study and providing constructive comments while receiving no compensation for his role in the study.
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