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Infectious Diseases

Incidence of Severe COVID-19 Illness Following Vaccination and Booster With BNT162b2, mRNA-1273, and Ad26.COV2.S Vaccines

Educational Objective
To identify the key insights or developments described in this article
1 Credit CME
JAMA
Published Online: September 26, 2022
Original Investigation
J. Daniel Kelly, MD, PhD1,2,3,4;
Samuel Leonard, MS1;
Katherine J. Hoggatt, PhD1,5;
W. John Boscardin, PhD2;
Emily N. Lum, MPH1;
Tristan A. Moss-Vazquez, BA1;
Raul Andino, PhD6;
Joseph K. Wong, MD1,5;
Amy Byers, PhD1;
Dawn M. Bravata, MD7,8,9;
Phyllis C. Tien, MD1,5;
Salomeh Keyhani, MD, MPH1,5
Author Affiliations
  • 1San Francisco VA Medical Center, San Francisco, California
  • 2Department of Epidemiology and Biostatistics, University of California, San Francisco
  • 3Institute for Global Health Sciences, University of California, San Francisco
  • 4F. I. Proctor Foundation, University of California, San Francisco
  • 5Department of Medicine, University of California, San Francisco
  • 6Department of Microbiology and Immunology, University of California, San Francisco
  • 7Department of Veterans Affairs Health Services and Development Center for Health Information and Communication and Department of Medicine, Richard L. Roudebush VA Medical Center, Indianapolis, Indiana
  • 8Department of Medicine, Indiana University School of Medicine, Indianapolis
  • 9Regenstrief Institute, Indianapolis, Indiana
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Key Points

Question  What is the incidence of severe COVID-19 illness following vaccination and booster with BNT162b2, mRNA-1273, and Ad26.COV2.S vaccines?

Findings  This retrospective cohort study included 1 610 719 participants receiving care at Veterans Health Administration facilities, followed up for 24 weeks (July 1, 2021, to May 30, 2022) after completing a COVID-19 vaccination series and booster. Overall, the incidence of hospitalization with COVID-19 pneumonia or death was 8.9 per 10 000 persons.

Meaning  In a US cohort, there was a low incidence of hospitalization with COVID-19 pneumonia or death following vaccination and booster during a period of Delta and Omicron variant predominance.

Abstract

Importance  Evidence describing the incidence of severe COVID-19 illness following vaccination and booster with BNT162b2, mRNA-1273, and Ad26.COV2.S vaccines is needed, particularly for high-risk populations.

Objective  To describe the incidence of severe COVID-19 illness among a cohort that received vaccination plus a booster vaccine dose.

Design, Setting, and Participants  Retrospective cohort study of adults receiving care at Veterans Health Administration facilities across the US who received a vaccination series plus 1 booster against SARS-CoV-2, conducted from July 1, 2021, to May 30, 2022. Patients were eligible if they had received a primary care visit in the prior 2 years and had documented receipt of all US Food and Drug Administration–authorized doses of the initial mRNA vaccine or viral vector vaccination series after December 11, 2020, and a subsequent documented booster dose between July 1, 2021, and April 29, 2022. The analytic cohort consisted of 1 610 719 participants.

Exposures  Receipt of any combination of mRNA-1273 (Moderna), BNT162b2 (Pfizer-BioNTech), and Ad26.COV2.S (Janssen/Johnson & Johnson) primary vaccination series and a booster dose.

Main Outcomes and Measures  Outcomes were breakthrough COVID-19 (symptomatic infection), hospitalization with COVID-19 pneumonia and/or death, and hospitalization with severe COVID-19 pneumonia and/or death. A subgroup analysis of nonoverlapping populations included those aged 65 years or older, those with high-risk comorbid conditions, and those with immunocompromising conditions.

Results  Of 1 610 719 participants, 1 100 280 (68.4%) were aged 65 years or older and 132 243 (8.2%) were female; 1 133 785 (70.4%) had high-risk comorbid conditions, 155 995 (9.6%) had immunocompromising conditions, and 1 467 879 (91.1%) received the same type of mRNA vaccine (initial series and booster). Over 24 weeks, 125.0 (95% CI, 123.3-126.8) per 10 000 persons had breakthrough COVID-19, 8.9 (95% CI, 8.5-9.4) per 10 000 persons were hospitalized with COVID-19 pneumonia or died, and 3.4 (95% CI, 3.1-3.7) per 10 000 persons were hospitalized with severe pneumonia or died. For high-risk populations, incidence of hospitalization with COVID-19 pneumonia or death was as follows: aged 65 years or older, 1.9 (95% CI, 1.4-2.6) per 10 000 persons; high-risk comorbid conditions, 6.7 (95% CI, 6.2-7.2) per 10 000 persons; and immunocompromising conditions, 39.6 (95% CI, 36.6-42.9) per 10 000 persons. Subgroup analyses of patients hospitalized with COVID-19 pneumonia or death by time after booster demonstrated similar incidence estimates among those aged 65 years or older and with high-risk comorbid conditions but not among those with immunocompromising conditions.

Conclusions and Relevance  In a US cohort of patients receiving care at Veterans Health Administration facilities during a period of Delta and Omicron variant predominance, there was a low incidence of hospitalization with COVID-19 pneumonia or death following vaccination and booster with any of BNT162b2, mRNA-1273, or Ad26.COV2.S vaccines.

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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.

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Infectious Diseases Vaccination Public Health Coronavirus (COVID-19)
Article Information

Corresponding Author: J. Daniel Kelly, MD, PhD, University of California, San Francisco, 550 16th St, San Francisco, CA 94143 (dan.kelly@ucsf.edu).

Accepted for Publication: September 14, 2022.

Published Online: September 26, 2022. doi:10.1001/jama.2022.17985

Author Contributions: Dr Kelly and Mr Leonard had full access to all of the data in the study and take responsibility for the integrity of the data and the accuracy of the data analysis.

Concept and design: Kelly, Leonard, Hoggatt, Andino, Wong, Keyhani.

Acquisition, analysis, or interpretation of data: Kelly, Leonard, Hoggatt, Boscardin, Lum, Moss-Vazquez, Andino, Byers, Bravata, Tien, Keyhani.

Drafting of the manuscript: Kelly, Leonard.

Critical revision of the manuscript for important intellectual content: Kelly, Hoggatt, Boscardin, Lum, Moss-Vazquez, Andino, Wong, Byers, Bravata, Tien, Keyhani.

Statistical analysis: Kelly, Leonard, Hoggatt, Boscardin, Byers, Keyhani.

Obtained funding: Kelly, Hoggatt, Bravata, Keyhani.

Administrative, technical, or material support: Kelly, Leonard, Lum, Moss-Vazquez, Andino, Wong, Bravata, Keyhani.

Supervision: Kelly, Andino, Keyhani.

Conflict of Interest Disclosures: Dr Andino reported receipt of grants from the US Centers for Disease Control and Prevention. Dr Byers reported receipt of a VA Research Career Scientist award outside the submitted work. Dr Bravata reported receipt of grants from the VA. Dr Tien reported receipt of grants from the National Institutes of Health, Merck, Gilead, and Lilly. No other disclosures were reported.

Funding/Support: This work was supported by VA Clinical Science Research and Development grant I01 CX002417 to Drs Kelly and Keyhani and National Institute of Allergy and Infectious Diseases (NIAID) grant K23 AI146268 to Dr Kelly.

Role of the Funder/Sponsor: The VA and the NIAID 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; or decision to submit the manuscript for publication.

Additional Contributions: We thank the US veterans who received vaccine booster doses and contributed data to this study. We appreciate our San Francisco–based chart review team and other VHA employees who have supported aspects of this study. We also appreciate Amy J. Markowitz, JD, University of California, San Francisco, for editorial feedback, for which she was compensated.

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