[Skip to Content]
[Skip to Content Landing]

Association of Primary and Booster Vaccination and Prior Infection With SARS-CoV-2 Infection and Severe COVID-19 Outcomes

Educational Objective
To identify the key insights or developments described in this article
1 Credit CME
Key Points

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.

Abstract

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.

Sign in to take quiz and track your certificates

Buy This Activity

JN Learning™ is the home for CME and MOC from the JAMA Network. Search by specialty or US state and earn AMA PRA Category 1 Credit(s)™ from articles, audio, Clinical Challenges and more. Learn more about CME/MOC

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.

Article Information

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 (lin@bios.unc.edu).

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.

References
1.
Lin  D-Y , Gu  Y , Wheeler  B ,  et al.  Effectiveness of Covid-19 vaccines over a 9-month period in North Carolina.   N Engl J Med. 2022;386(10):933-941. doi:10.1056/NEJMoa2117128PubMedGoogle ScholarCrossref
2.
US Dept of Health and Human Services. COVID-19 Pandemic Response, Laboratory Data Reporting: CARES Act Section 18115. Updated January 8, 2021. Accessed January 11, 2022. https://www.hhs.gov/sites/default/files/covid-19-laboratory-data-reporting-guidance.pdf
3.
Andersen  PK , Gill  RD .  Cox’s regression model for counting processes: a large sample study.   Ann Stat. 1982;10(4):1100-1120. doi:10.1214/aos/1176345976Google ScholarCrossref
4.
Cox  DR .  Regression models and life-tables.   J R Stat Soc B. 1972;34(2):187-202.Google Scholar
5.
Fintzi  J , Follmann  D .  Assessing vaccine durability in randomized trials following placebo crossover.   Stat Med. 2021;40(27):5983-6007. doi:10.1002/sim.9001PubMedGoogle ScholarCrossref
6.
Andrews  N , Stowe  J , Kirsebom  F ,  et al.  Covid-19 vaccine effectiveness against the omicron (B.1.1.529) variant.   N Engl J Med. 2022;386(16):1532-1546. doi:10.1056/NEJMoa2119451PubMedGoogle ScholarCrossref
7.
Abu-Raddad  LJ , Chemaitelly  H , Ayoub  HH ,  et al.  Effect of mRNA vaccine boosters against SARS-CoV-2 omicron infection in Qatar.   N Engl J Med. 2022;386(19):1804-1816. doi:10.1056/NEJMoa2200797PubMedGoogle ScholarCrossref
8.
Mayr  FB , Talisa  VB , Shaikh  O , Yende  S , Butt  AA .  Effectiveness of homologous or heterologous Covid-19 boosters in veterans.   N Engl J Med. 2022;386(14):1375-1377. doi:10.1056/NEJMc2200415PubMedGoogle ScholarCrossref
9.
Accorsi  EK , Britton  A , Fleming-Dutra  KE ,  et al.  Association between 3 doses of mRNA COVID-19 vaccine and symptomatic infection caused by the SARS-CoV-2 Omicron and Delta variants.   JAMA. 2022;327(7):639-651. doi:10.1001/jama.2022.0470PubMedGoogle ScholarCrossref
10.
Goldberg  Y , Mandel  M , Bar-On  YM ,  et al.  Protection and waning of natural and hybrid immunity to SARS-CoV-2.   N Engl J Med. 2022;386(23):2201-2212. doi:10.1056/NEJMoa2118946PubMedGoogle ScholarCrossref
11.
Hall  V , Foulkes  S , Insalata  F ,  et al; SIREN Study Group.  Protection against SARS-CoV-2 after Covid-19 vaccination and previous infection.   N Engl J Med. 2022;386(13):1207-1220. doi:10.1056/NEJMoa2118691PubMedGoogle ScholarCrossref
12.
Altarawneh  HN , Chemaitelly  H , Hasan  MR ,  et al.  Protection against the omicron variant from previous SARS-CoV-2 infection.   N Engl J Med. 2022;386(13):1288-1290. doi:10.1056/NEJMc2200133PubMedGoogle ScholarCrossref
13.
Chemaitelly  H , Ayoub  HH , Coyle  P ,  et al.  Protection of omicron sub-lineage infection against reinfection with another Omicron sub-lineage.   Nat Commun. 2022;13(1):4675. doi:10.1038/s41467-022-32363-4PubMedGoogle ScholarCrossref
Close
Want full access to the AMA Ed Hub?
After you sign up for AMA Membership, make sure you sign in or create a Physician account with the AMA in order to access all learning activities on the AMA Ed Hub
Buy this activity
Close
Want full access to the AMA Ed Hub?
After you sign up for AMA Membership, make sure you sign in or create a Physician account with the AMA in order to access all learning activities on the AMA Ed Hub
Buy this activity
Close
With a personal account, you can:
  • Access free activities and track your credits
  • Personalize content alerts
  • Customize your interests
  • Fully personalize your learning experience
Education Center Collection Sign In Modal Right
Close

Name Your Search

Save Search
With a personal account, you can:
  • Access free activities and track your credits
  • Personalize content alerts
  • Customize your interests
  • Fully personalize your learning experience
Close
Close

Lookup An Activity

or

My Saved Searches

You currently have no searches saved.

Close

My Saved Courses

You currently have no courses saved.

Close