Observational Study

. 2024 Feb;177(2):165-176.

doi: 10.7326/M23-1754. Epub 2024 Jan 9.

Real-World Effectiveness of BNT162b2 Against Infection and Severe Diseases in Children and Adolescents

Qiong Wu¹, Jiayi Tong¹, Bingyu Zhang², Dazheng Zhang¹, Jiajie Chen¹, Yuqing Lei¹, Yiwen Lu², Yudong Wang¹, Lu Li², Yishan Shen², Jie Xu³, L Charles Bailey⁴, Jiang Bian³, Dimitri A Christakis⁵, Megan L Fitzgerald⁶, Kathryn Hirabayashi⁴, Ravi Jhaveri⁷, Alka Khaitan⁸, Tianchen Lyu³, Suchitra Rao⁹, Hanieh Razzaghi⁴, Hayden T Schwenk¹⁰, Fei Wang¹¹, Margot I Gage Witvliet¹², Eric J Tchetgen Tchetgen¹³, Jeffrey S Morris¹³, Christopher B Forrest⁴, Yong Chen¹⁴

Affiliations

¹ The Center for Health Analytics and Synthesis of Evidence (CHASE), Department of Biostatistics, Epidemiology, and Informatics, University of Pennsylvania Perelman School of Medicine, Philadelphia, Pennsylvania (Q.W., J.T., D.Z., J.C., Y.Lei, Y.W.).
² The Center for Health Analytics and Synthesis of Evidence (CHASE), The Graduate Group in Applied Mathematics and Computational Science, School of Arts and Sciences, University of Pennsylvania, Philadelphia, Pennsylvania (B.Z., Y.Lu, L.L., Y.S.).
³ Department of Health Outcomes Biomedical Informatics, University of Florida, Gainesville, Florida (J.X., J.B., T.L.).
⁴ Applied Clinical Research Center, Children's Hospital of Philadelphia, Philadelphia, Pennsylvania (L.C.B., K.H., H.R., C.B.F.).
⁵ Center for Child Health, Behavior, and Development, Seattle Children's Research Institute, Seattle, Washington (D.A.C.).
⁶ Department of Medicine, Grossman School of Medicine, New York University, New York, New York (M.L.F.).
⁷ Division of Pediatric Infectious Diseases, Ann & Robert H. Lurie Children's Hospital of Chicago, Chicago, Illinois (R.J.).
⁸ Department of Pediatrics, Ryan White Center for Pediatric Infectious Diseases and Global Health, Indiana University School of Medicine, Indianapolis, Indiana (A.K.).
⁹ Department of Pediatrics, University of Colorado School of Medicine and Children's Hospital Colorado, Aurora, Colorado (S.R.).
¹⁰ Department of Pediatrics, Stanford School of Medicine, Stanford, California (H.T.S.).
¹¹ Department of Population Health Sciences, Weill Cornell Medicine, New York, New York (F.W.).
¹² Department of Sociology, Social Work and Criminal Justice, Lamar University, Beaumont, Texas (M.I.G.W.).
¹³ Department of Biostatistics, Epidemiology, and Informatics, University of Pennsylvania Perelman School of Medicine, Philadelphia, Pennsylvania (E.J.T.T., J.S.M.).
¹⁴ The Center for Health Analytics and Synthesis of Evidence (CHASE), Department of Biostatistics, Epidemiology, and Informatics, University of Pennsylvania Perelman School of Medicine, and The Graduate Group in Applied Mathematics and Computational Science, School of Arts and Sciences, University of Pennsylvania, Leonard Davis Institute of Health Economics, Penn Medicine Center for Evidence-based Practice (CEP), and Penn Institute for Biomedical Informatics (IBI), Philadelphia, Pennsylvania (Y.C.).

PMID: 38190711
PMCID: PMC11956830
DOI: 10.7326/M23-1754

Observational Study

Real-World Effectiveness of BNT162b2 Against Infection and Severe Diseases in Children and Adolescents

Qiong Wu et al. Ann Intern Med. 2024 Feb.

. 2024 Feb;177(2):165-176.

doi: 10.7326/M23-1754. Epub 2024 Jan 9.

Authors

Affiliations

¹ The Center for Health Analytics and Synthesis of Evidence (CHASE), Department of Biostatistics, Epidemiology, and Informatics, University of Pennsylvania Perelman School of Medicine, Philadelphia, Pennsylvania (Q.W., J.T., D.Z., J.C., Y.Lei, Y.W.).
² The Center for Health Analytics and Synthesis of Evidence (CHASE), The Graduate Group in Applied Mathematics and Computational Science, School of Arts and Sciences, University of Pennsylvania, Philadelphia, Pennsylvania (B.Z., Y.Lu, L.L., Y.S.).
³ Department of Health Outcomes Biomedical Informatics, University of Florida, Gainesville, Florida (J.X., J.B., T.L.).
⁴ Applied Clinical Research Center, Children's Hospital of Philadelphia, Philadelphia, Pennsylvania (L.C.B., K.H., H.R., C.B.F.).
⁵ Center for Child Health, Behavior, and Development, Seattle Children's Research Institute, Seattle, Washington (D.A.C.).
⁶ Department of Medicine, Grossman School of Medicine, New York University, New York, New York (M.L.F.).
⁷ Division of Pediatric Infectious Diseases, Ann & Robert H. Lurie Children's Hospital of Chicago, Chicago, Illinois (R.J.).
⁸ Department of Pediatrics, Ryan White Center for Pediatric Infectious Diseases and Global Health, Indiana University School of Medicine, Indianapolis, Indiana (A.K.).
⁹ Department of Pediatrics, University of Colorado School of Medicine and Children's Hospital Colorado, Aurora, Colorado (S.R.).
¹⁰ Department of Pediatrics, Stanford School of Medicine, Stanford, California (H.T.S.).
¹¹ Department of Population Health Sciences, Weill Cornell Medicine, New York, New York (F.W.).
¹² Department of Sociology, Social Work and Criminal Justice, Lamar University, Beaumont, Texas (M.I.G.W.).
¹³ Department of Biostatistics, Epidemiology, and Informatics, University of Pennsylvania Perelman School of Medicine, Philadelphia, Pennsylvania (E.J.T.T., J.S.M.).
¹⁴ The Center for Health Analytics and Synthesis of Evidence (CHASE), Department of Biostatistics, Epidemiology, and Informatics, University of Pennsylvania Perelman School of Medicine, and The Graduate Group in Applied Mathematics and Computational Science, School of Arts and Sciences, University of Pennsylvania, Leonard Davis Institute of Health Economics, Penn Medicine Center for Evidence-based Practice (CEP), and Penn Institute for Biomedical Informatics (IBI), Philadelphia, Pennsylvania (Y.C.).

PMID: 38190711
PMCID: PMC11956830
DOI: 10.7326/M23-1754

Abstract

Background: The efficacy of the BNT162b2 vaccine in pediatrics was assessed by randomized trials before the Omicron variant's emergence. The long-term durability of vaccine protection in this population during the Omicron period remains limited.

Objective: To assess the effectiveness of BNT162b2 in preventing infection and severe diseases with various strains of the SARS-CoV-2 virus in previously uninfected children and adolescents.

Design: Comparative effectiveness research accounting for underreported vaccination in 3 study cohorts: adolescents (12 to 20 years) during the Delta phase and children (5 to 11 years) and adolescents (12 to 20 years) during the Omicron phase.

Setting: A national collaboration of pediatric health systems (PEDSnet).

Participants: 77 392 adolescents (45 007 vaccinated) during the Delta phase and 111 539 children (50 398 vaccinated) and 56 080 adolescents (21 180 vaccinated) during the Omicron phase.

Intervention: First dose of the BNT162b2 vaccine versus no receipt of COVID-19 vaccine.

Measurements: Outcomes of interest include documented infection, COVID-19 illness severity, admission to an intensive care unit (ICU), and cardiac complications. The effectiveness was reported as (1-relative risk)*100, with confounders balanced via propensity score stratification.

Results: During the Delta period, the estimated effectiveness of the BNT162b2 vaccine was 98.4% (95% CI, 98.1% to 98.7%) against documented infection among adolescents, with no statistically significant waning after receipt of the first dose. An analysis of cardiac complications did not suggest a statistically significant difference between vaccinated and unvaccinated groups. During the Omicron period, the effectiveness against documented infection among children was estimated to be 74.3% (CI, 72.2% to 76.2%). Higher levels of effectiveness were seen against moderate or severe COVID-19 (75.5% [CI, 69.0% to 81.0%]) and ICU admission with COVID-19 (84.9% [CI, 64.8% to 93.5%]). Among adolescents, the effectiveness against documented Omicron infection was 85.5% (CI, 83.8% to 87.1%), with 84.8% (CI, 77.3% to 89.9%) against moderate or severe COVID-19, and 91.5% (CI, 69.5% to 97.6%) against ICU admission with COVID-19. The effectiveness of the BNT162b2 vaccine against the Omicron variant declined 4 months after the first dose and then stabilized. The analysis showed a lower risk for cardiac complications in the vaccinated group during the Omicron variant period.

Limitation: Observational study design and potentially undocumented infection.

Conclusion: This study suggests that BNT162b2 was effective for various COVID-19-related outcomes in children and adolescents during the Delta and Omicron periods, and there is some evidence of waning effectiveness over time.

Primary funding source: National Institutes of Health.

PubMed Disclaimer

Conflict of interest statement

Disclosures: Disclosures can be viewed at www.acponline.org/authors/icmje/ConflictOfInterestForms.do?msNum=M23-1754.

Figures

**Figure 1.**
Selection of participants for the three study cohorts evaluating the effectiveness of the BNT162b2 vaccine in preventing infection with SARS-CoV-2 in (*Study cohort 1*) adolescents aged 12-20 years during the period when the Delta variant was prevalent, (*Study cohort 2*) children aged 5 to 11 years and (*Study cohort 3*) adolescents aged 12 to 20 years during the period when the Omicron variant was prevalent.

**Figure 2.**
Stratified effectiveness of the BNT162b2 vaccine in preventing infection with SARS-CoV-2 in children and adolescents by 2-month intervals since receipt of the first dose

See this image and copyright information in PMC

Update of

Real-world Effectiveness of BNT162b2 Against Infection and Severe Diseases in Children and Adolescents.
Wu Q, Tong J, Zhang B, Zhang D, Chen J, Lei Y, Lu Y, Wang Y, Li L, Shen Y, Xu J, Bailey LC, Bian J, Christakis DA, Fitzgerald ML, Hirabayashi K, Jhaveri R, Khaitan A, Lyu T, Rao S, Razzaghi H, Schwenk HT, Wang F, Witvliet MI, Tchetgen EJT, Morris JS, Forrest CB, Chen Y. Wu Q, et al. medRxiv [Preprint]. 2023 Nov 13:2023.06.16.23291515. doi: 10.1101/2023.06.16.23291515. medRxiv. 2023. Update in: Ann Intern Med. 2024 Feb;177(2):165-176. doi: 10.7326/M23-1754. PMID: 38014095 Free PMC article. Updated. Preprint.

Cited by

COVID-19 vaccination-related tinnitus is associated with pre-vaccination metabolic disorders.
Wang W, Yellamsetty A, Edmonds RM, Barcavage SR, Bao S. Wang W, et al. Front Pharmacol. 2024 May 22;15:1374320. doi: 10.3389/fphar.2024.1374320. eCollection 2024. Front Pharmacol. 2024. PMID: 38841369 Free PMC article.
A latent transfer learning method for estimating hospital-specific post-acute healthcare demands following SARS-CoV-2 infection.
Wu Q, Pajor NM, Lu Y, Wolock CJ, Tong J, Lorman V, Johnson KB, Moore JH, Forrest CB, Asch DA, Chen Y. Wu Q, et al. Patterns (N Y). 2024 Oct 24;5(11):101079. doi: 10.1016/j.patter.2024.101079. eCollection 2024 Nov 8. Patterns (N Y). 2024. PMID: 39568467 Free PMC article.
Vaccine Effectiveness Among 5- to 17-year-old Individuals with Prior SARS-CoV-2 Infection: An EHR-Based Target Trial Emulation Study from the RECOVER Project.
Chen Y, Lei Y, Chen J, Wu Q, Zhou T, Zhang B, Becich M, Bisyuk Y, Blecker S, Chrischilles E, Christakis D, Cowell L, Cummins M, Fernandez S, Fort D, Gonzalez S, Herring S, Horne B, Horowitz C, Liu M, Kim S, Mirhaji P, Mosa A, Muszynski J, Paules C, Sato A, Schwenk H, Sengupta S, Suresh S, Taylor B, Williams D, He Y, Morris J, Jhaveri R, Forrest C. Chen Y, et al. Res Sq [Preprint]. 2025 Jul 3:rs.3.rs-6945998. doi: 10.21203/rs.3.rs-6945998/v1. Res Sq. 2025. PMID: 40630514 Free PMC article. Preprint.
Communication-Efficient Distributed Estimation of Causal Effects With High-Dimensional Data.
Wang X, Tong J, Peng S, Chen Y, Ning Y. Wang X, et al. Stat. 2024 Sep;13(3):e70006. doi: 10.1002/sta4.70006. Epub 2024 Sep 9. Stat. 2024. PMID: 40642290 Free PMC article.
Leveraging undecided cases in chart-reviewed phenotypes to enhance EHR-based association studies.
Jian X, Zhang D, Yu Z, Xu H, Bian J, Wu Y, Tong J, Chen Y. Jian X, et al. J Biomed Inform. 2025 Jun;166:104839. doi: 10.1016/j.jbi.2025.104839. Epub 2025 Apr 30. J Biomed Inform. 2025. PMID: 40316004 Free PMC article.

See all "Cited by" articles

References

1. Flaxman S, Whittaker C, Semenova E, Rashid T, Parks RM, Blenkinsop A, et al. Assessment of COVID-19 as the Underlying Cause of Death Among Children and Young People Aged 0 to 19 Years in the US. JAMA Netw Open. 2023. Jan 30;6(1):e2253590. - PMC - PubMed
1. Frenck RW, Klein NP, Kitchin N, Gurtman A, Absalon J, Lockhart S, et al. Safety, Immunogenicity, and Efficacy of the BNT162b2 Covid-19 Vaccine in Adolescents. New England Journal of Medicine. 2021. Jul 15;385(3):239–50. - PMC - PubMed
1. Walter EB, Talaat KR, Sabharwal C, Gurtman A, Lockhart S, Paulsen GC, et al. Evaluation of the BNT162b2 Covid-19 Vaccine in Children 5 to 11 Years of Age. New England Journal of Medicine. 2022. Jan 6;386(1):35–46. - PMC - PubMed
1. Chemaitelly H, AlMukdad S, Ayoub HH, Altarawneh HN, Coyle P, Tang P, et al. Covid-19 Vaccine Protection among Children and Adolescents in Qatar. New England Journal of Medicine. 2022;387(20). - PMC - PubMed
1. Cohen-Stavi CJ, Magen O, Barda N, Yaron S, Peretz A, Netzer D, et al. BNT162b2 Vaccine Effectiveness against Omicron in Children 5 to 11 Years of Age. New England Journal of Medicine. 2022. Jul 21;387(3):227–36. - PMC - PubMed

Publication types

Actions

MeSH terms

Actions
Actions
Actions
Actions
Actions
Actions
Actions
Actions
Actions

Save citation to file

Email citation

Add to Collections

Add to My Bibliography

Your saved search

Create a file for external citation management software

Your RSS Feed

Real-World Effectiveness of BNT162b2 Against Infection and Severe Diseases in Children and Adolescents

Affiliations

Real-World Effectiveness of BNT162b2 Against Infection and Severe Diseases in Children and Adolescents

Authors

Affiliations

Abstract

Conflict of interest statement

Figures

Update of

Similar articles

Cited by

References

Publication types

MeSH terms

Substances

Grants and funding

LinkOut - more resources

Full Text Sources

Medical

Miscellaneous

Abstract

Conflict of interest statement

Figures

Update of

Similar articles

Cited by

References

Publication types

MeSH terms

Substances

Related information

Grants and funding

LinkOut - more resources

Full Text Sources

Medical

Miscellaneous