Real-world effectiveness and causal mediation study of BNT162b2 on long COVID risks in children and adolescentsResearch in context
Summary: Background: The impact of pre-infection vaccination on the risk of long COVID remains unclear in the pediatric population. We aim to assess the effectiveness of BNT162b2 on long COVID risks with various strains of the SARS-CoV-2 virus in children and adolescents, using comparative effectiv...
Saved in:
| Main Authors: | , , , , , , , , , , , , , , , , , , , , , , , , , , |
|---|---|
| Format: | Article |
| Language: | English |
| Published: |
Elsevier
2025-01-01
|
| Series: | EClinicalMedicine |
| Subjects: | |
| Online Access: | http://www.sciencedirect.com/science/article/pii/S2589537024005418 |
| Tags: |
Add Tag
No Tags, Be the first to tag this record!
|
| _version_ | 1832591746087780352 |
|---|---|
| author | Qiong Wu Bingyu Zhang Jiayi Tong L. Charles Bailey H. Timothy Bunnell Jiajie Chen Elizabeth A. Chrischilles Dimitri A. Christakis Stephen M. Downs Kathryn Hirabayashi Aaron D. Mishkin Abu S.M. Mosa Nathan M. Pajor Suchitra Rao Hanieh Razzaghi Hayden T. Schwenk Marion R. Sills Huiyuan Wang Linbo Wang Yudong Wang Dazheng Zhang Ting Zhou Ravi Jhaveri Eric J. Tchetgen Tchetgen Jeffrey S. Morris Christopher B. Forrest Yong Chen |
| author_facet | Qiong Wu Bingyu Zhang Jiayi Tong L. Charles Bailey H. Timothy Bunnell Jiajie Chen Elizabeth A. Chrischilles Dimitri A. Christakis Stephen M. Downs Kathryn Hirabayashi Aaron D. Mishkin Abu S.M. Mosa Nathan M. Pajor Suchitra Rao Hanieh Razzaghi Hayden T. Schwenk Marion R. Sills Huiyuan Wang Linbo Wang Yudong Wang Dazheng Zhang Ting Zhou Ravi Jhaveri Eric J. Tchetgen Tchetgen Jeffrey S. Morris Christopher B. Forrest Yong Chen |
| author_sort | Qiong Wu |
| collection | DOAJ |
| description | Summary: Background: The impact of pre-infection vaccination on the risk of long COVID remains unclear in the pediatric population. We aim to assess the effectiveness of BNT162b2 on long COVID risks with various strains of the SARS-CoV-2 virus in children and adolescents, using comparative effectiveness methods. We further explore if such pre-infection vaccination can mitigate the risk of long COVID beyond its established protective benefits against SARS-CoV-2 infection using causal mediation analysis. Methods: We conducted real-world vaccine effectiveness study and mediation analysis using data from twenty health systems in the RECOVER PCORnet electronic health record (EHR) Program. Three independent cohorts were constructed including adolescents (12–20 years) during the Delta phase (July 1–November 30, 2021), children (5–11 years) and adolescents (12–20 years) during the Omicron phase (January 1–November 30, 2022). The intervention is first dose of the BNT162b2 vaccine in comparison with no receipt of COVID-19 vaccine. The outcomes of interest include conclusive or probable diagnosis of long COVID following a documented SARS-CoV-2 infection, and body-system-specific condition clusters of post-acute sequelae of SARS-CoV-2 infection (PASC), such as cardiac, gastrointestinal, musculoskeletal, respiratory, and syndromic categories. The effectiveness was reported as (1-relative risk)∗100 and mediating effects were reported as relative risks. Findings: 112,590 adolescents (88,811 vaccinated) were included in the cohort for the analysis against Delta variant, and 188,894 children (101,277 vaccinated), and 84,735 adolescents (37,724 vaccinated) were included for the analysis against Omicron variant. During the Delta period, the estimated effectiveness of the BNT162b2 vaccine against long COVID among adolescents was 95.4% (95% CI: 90.9%–97.7%). During the Omicron phase, the estimated effectiveness against long COVID among children was 60.2% (95% CI: 40.3%–73.5%) and 75.1% (95% CI: 50.4%–87.5%) among adolescents. The direct effect of vaccination, defined as the effect beyond their impact on SARS-CoV-2 infections, was found to be statistically non-significant in all three study cohorts, with estimated relative risk of 1.08 (95% CI: 0.75–1.55) in the Delta study among adolescents, 1.24 (95% CI: 0.92–1.66) among children and 0.91 (95% CI: 0.69–1.19) among adolescents in the Omicron studies. Meanwhile, the estimated indirect effects, which are effects through protecting SARS-CoV-2 infections, were estimated as 0.04 (95% CI: 0.03–0.05) among adolescents during Delta phase, 0.31 (95% CI: 0.23–0.42) among children and 0.21 (95% CI: 0.16–0.27) among adolescents during the Omicron period. Interpretation: Our study suggests that BNT162b2 was effective in reducing risk of long COVID outcomes in children and adolescents during the Delta and Omicron periods. The mediation analysis indicates the vaccine’s effectiveness is primarily derived from its role in reducing the risk of SARS-CoV-2 infection. Funding: National Institutes of Health. |
| format | Article |
| id | doaj-art-07113564bd944de1a14bb0a80886c1e1 |
| institution | Kabale University |
| issn | 2589-5370 |
| language | English |
| publishDate | 2025-01-01 |
| publisher | Elsevier |
| record_format | Article |
| series | EClinicalMedicine |
| spelling | doaj-art-07113564bd944de1a14bb0a80886c1e12025-01-22T05:43:09ZengElsevierEClinicalMedicine2589-53702025-01-0179102962Real-world effectiveness and causal mediation study of BNT162b2 on long COVID risks in children and adolescentsResearch in contextQiong Wu0Bingyu Zhang1Jiayi Tong2L. Charles Bailey3H. Timothy Bunnell4Jiajie Chen5Elizabeth A. Chrischilles6Dimitri A. Christakis7Stephen M. Downs8Kathryn Hirabayashi9Aaron D. Mishkin10Abu S.M. Mosa11Nathan M. Pajor12Suchitra Rao13Hanieh Razzaghi14Hayden T. Schwenk15Marion R. Sills16Huiyuan Wang17Linbo Wang18Yudong Wang19Dazheng Zhang20Ting Zhou21Ravi Jhaveri22Eric J. Tchetgen Tchetgen23Jeffrey S. Morris24Christopher B. Forrest25Yong Chen26Department of Biostatistics and Health Data Science, University of Pittsburgh, Pittsburgh, PA, USA; Department of Biostatistics, Epidemiology, and Informatics, University of Pennsylvania Perelman School of Medicine, Philadelphia, PA, USA; The Center for Health AI and Synthesis of Evidence (CHASE), University of Pennsylvania, Philadelphia, PA, USAThe Center for Health AI and Synthesis of Evidence (CHASE), University of Pennsylvania, Philadelphia, PA, USA; The Graduate Group in Applied Mathematics and Computational Science, School of Arts and Sciences, University of Pennsylvania, Philadelphia, PA, USADepartment of Biostatistics, Epidemiology, and Informatics, University of Pennsylvania Perelman School of Medicine, Philadelphia, PA, USA; The Center for Health AI and Synthesis of Evidence (CHASE), University of Pennsylvania, Philadelphia, PA, USA; Department of Biostatistics, Johns Hopkins Bloomberg School of Public Health, Baltimore, MD, USAApplied Clinical Research Center, The Children’s Hospital of Philadelphia, Philadelphia, PA, USABiomedical Research Informatics Center, Nemours Children’s Health, Nemours Children’s Hospital, Wilmington, DE, USADepartment of Biostatistics, Epidemiology, and Informatics, University of Pennsylvania Perelman School of Medicine, Philadelphia, PA, USA; The Center for Health AI and Synthesis of Evidence (CHASE), University of Pennsylvania, Philadelphia, PA, USADepartment of Epidemiology, College of Public Health, University of Iowa, Iowa City, IA, USACenter for Child Health, Behavior and Development, Seattle Children’s Research Institute, Seattle, WA, USADepartment of Pediatrics, Atrium Health Wake Forest Baptist, Winston-Salem, NC, USAApplied Clinical Research Center, The Children’s Hospital of Philadelphia, Philadelphia, PA, USASection of Infectious Diseases, Lewis Katz School of Medicine at Temple University, Philadelphia, PA, USABiomedical Informatics, Biostatistics and Medical Epidemiology, University of Missouri School of Medicine, Columbia, MO, USADivision of Pulmonary Medicine, Cincinnati Children’s Hospital Medical Center and University of Cincinnati College of Medicine, Cincinnati, OH, USADepartment of Pediatrics, University of Colorado School of Medicine and Children’s Hospital Colorado, Aurora, CO, USAApplied Clinical Research Center, The Children’s Hospital of Philadelphia, Philadelphia, PA, USADepartment of Pediatrics, Stanford School of Medicine, Stanford, CA, USADepartment of Pediatrics, University of Colorado School of Medicine and Children’s Hospital Colorado, Aurora, CO, USA; Department of Research, OCHIN, Inc., Portland, OR, USADepartment of Biostatistics, Epidemiology, and Informatics, University of Pennsylvania Perelman School of Medicine, Philadelphia, PA, USA; The Center for Health AI and Synthesis of Evidence (CHASE), University of Pennsylvania, Philadelphia, PA, USADepartment of Statistical Sciences, University of Toronto, Toronto, Ontario, CanadaDepartment of Biostatistics, Epidemiology, and Informatics, University of Pennsylvania Perelman School of Medicine, Philadelphia, PA, USA; The Center for Health AI and Synthesis of Evidence (CHASE), University of Pennsylvania, Philadelphia, PA, USADepartment of Biostatistics, Epidemiology, and Informatics, University of Pennsylvania Perelman School of Medicine, Philadelphia, PA, USA; The Center for Health AI and Synthesis of Evidence (CHASE), University of Pennsylvania, Philadelphia, PA, USADepartment of Biostatistics, Epidemiology, and Informatics, University of Pennsylvania Perelman School of Medicine, Philadelphia, PA, USA; The Center for Health AI and Synthesis of Evidence (CHASE), University of Pennsylvania, Philadelphia, PA, USADivision of Infectious Diseases, Ann & Robert H. Lurie Children’s Hospital of Chicago, Chicago, IL, USADepartment of Biostatistics, Epidemiology, and Informatics, University of Pennsylvania Perelman School of Medicine, Philadelphia, PA, USADepartment of Biostatistics, Epidemiology, and Informatics, University of Pennsylvania Perelman School of Medicine, Philadelphia, PA, USA; Corresponding author.Applied Clinical Research Center, The Children’s Hospital of Philadelphia, Philadelphia, PA, USA; Corresponding author.Department of Biostatistics, Epidemiology, and Informatics, University of Pennsylvania Perelman School of Medicine, Philadelphia, PA, USA; The Center for Health AI and Synthesis of Evidence (CHASE), University of Pennsylvania, Philadelphia, PA, USA; The Graduate Group in Applied Mathematics and Computational Science, School of Arts and Sciences, University of Pennsylvania, Philadelphia, PA, USA; Leonard Davis Institute of Health Economics, Philadelphia, PA, USA; Penn Medicine Center for Evidence-based Practice (CEP), Philadelphia, PA, USA; Penn Institute for Biomedical Informatics (IBI), Philadelphia, PA, USA; Corresponding author. Department of Biostatistics, Epidemiology, and Informatics, University of Pennsylvania Perelman School of Medicine, Philadelphia, PA, USA.Summary: Background: The impact of pre-infection vaccination on the risk of long COVID remains unclear in the pediatric population. We aim to assess the effectiveness of BNT162b2 on long COVID risks with various strains of the SARS-CoV-2 virus in children and adolescents, using comparative effectiveness methods. We further explore if such pre-infection vaccination can mitigate the risk of long COVID beyond its established protective benefits against SARS-CoV-2 infection using causal mediation analysis. Methods: We conducted real-world vaccine effectiveness study and mediation analysis using data from twenty health systems in the RECOVER PCORnet electronic health record (EHR) Program. Three independent cohorts were constructed including adolescents (12–20 years) during the Delta phase (July 1–November 30, 2021), children (5–11 years) and adolescents (12–20 years) during the Omicron phase (January 1–November 30, 2022). The intervention is first dose of the BNT162b2 vaccine in comparison with no receipt of COVID-19 vaccine. The outcomes of interest include conclusive or probable diagnosis of long COVID following a documented SARS-CoV-2 infection, and body-system-specific condition clusters of post-acute sequelae of SARS-CoV-2 infection (PASC), such as cardiac, gastrointestinal, musculoskeletal, respiratory, and syndromic categories. The effectiveness was reported as (1-relative risk)∗100 and mediating effects were reported as relative risks. Findings: 112,590 adolescents (88,811 vaccinated) were included in the cohort for the analysis against Delta variant, and 188,894 children (101,277 vaccinated), and 84,735 adolescents (37,724 vaccinated) were included for the analysis against Omicron variant. During the Delta period, the estimated effectiveness of the BNT162b2 vaccine against long COVID among adolescents was 95.4% (95% CI: 90.9%–97.7%). During the Omicron phase, the estimated effectiveness against long COVID among children was 60.2% (95% CI: 40.3%–73.5%) and 75.1% (95% CI: 50.4%–87.5%) among adolescents. The direct effect of vaccination, defined as the effect beyond their impact on SARS-CoV-2 infections, was found to be statistically non-significant in all three study cohorts, with estimated relative risk of 1.08 (95% CI: 0.75–1.55) in the Delta study among adolescents, 1.24 (95% CI: 0.92–1.66) among children and 0.91 (95% CI: 0.69–1.19) among adolescents in the Omicron studies. Meanwhile, the estimated indirect effects, which are effects through protecting SARS-CoV-2 infections, were estimated as 0.04 (95% CI: 0.03–0.05) among adolescents during Delta phase, 0.31 (95% CI: 0.23–0.42) among children and 0.21 (95% CI: 0.16–0.27) among adolescents during the Omicron period. Interpretation: Our study suggests that BNT162b2 was effective in reducing risk of long COVID outcomes in children and adolescents during the Delta and Omicron periods. The mediation analysis indicates the vaccine’s effectiveness is primarily derived from its role in reducing the risk of SARS-CoV-2 infection. Funding: National Institutes of Health.http://www.sciencedirect.com/science/article/pii/S2589537024005418Causal mediation analysisLong COVIDPediatric researchReal-world effectivenessVaccination |
| spellingShingle | Qiong Wu Bingyu Zhang Jiayi Tong L. Charles Bailey H. Timothy Bunnell Jiajie Chen Elizabeth A. Chrischilles Dimitri A. Christakis Stephen M. Downs Kathryn Hirabayashi Aaron D. Mishkin Abu S.M. Mosa Nathan M. Pajor Suchitra Rao Hanieh Razzaghi Hayden T. Schwenk Marion R. Sills Huiyuan Wang Linbo Wang Yudong Wang Dazheng Zhang Ting Zhou Ravi Jhaveri Eric J. Tchetgen Tchetgen Jeffrey S. Morris Christopher B. Forrest Yong Chen Real-world effectiveness and causal mediation study of BNT162b2 on long COVID risks in children and adolescentsResearch in context EClinicalMedicine Causal mediation analysis Long COVID Pediatric research Real-world effectiveness Vaccination |
| title | Real-world effectiveness and causal mediation study of BNT162b2 on long COVID risks in children and adolescentsResearch in context |
| title_full | Real-world effectiveness and causal mediation study of BNT162b2 on long COVID risks in children and adolescentsResearch in context |
| title_fullStr | Real-world effectiveness and causal mediation study of BNT162b2 on long COVID risks in children and adolescentsResearch in context |
| title_full_unstemmed | Real-world effectiveness and causal mediation study of BNT162b2 on long COVID risks in children and adolescentsResearch in context |
| title_short | Real-world effectiveness and causal mediation study of BNT162b2 on long COVID risks in children and adolescentsResearch in context |
| title_sort | real world effectiveness and causal mediation study of bnt162b2 on long covid risks in children and adolescentsresearch in context |
| topic | Causal mediation analysis Long COVID Pediatric research Real-world effectiveness Vaccination |
| url | http://www.sciencedirect.com/science/article/pii/S2589537024005418 |
| work_keys_str_mv | AT qiongwu realworldeffectivenessandcausalmediationstudyofbnt162b2onlongcovidrisksinchildrenandadolescentsresearchincontext AT bingyuzhang realworldeffectivenessandcausalmediationstudyofbnt162b2onlongcovidrisksinchildrenandadolescentsresearchincontext AT jiayitong realworldeffectivenessandcausalmediationstudyofbnt162b2onlongcovidrisksinchildrenandadolescentsresearchincontext AT lcharlesbailey realworldeffectivenessandcausalmediationstudyofbnt162b2onlongcovidrisksinchildrenandadolescentsresearchincontext AT htimothybunnell realworldeffectivenessandcausalmediationstudyofbnt162b2onlongcovidrisksinchildrenandadolescentsresearchincontext AT jiajiechen realworldeffectivenessandcausalmediationstudyofbnt162b2onlongcovidrisksinchildrenandadolescentsresearchincontext AT elizabethachrischilles realworldeffectivenessandcausalmediationstudyofbnt162b2onlongcovidrisksinchildrenandadolescentsresearchincontext AT dimitriachristakis realworldeffectivenessandcausalmediationstudyofbnt162b2onlongcovidrisksinchildrenandadolescentsresearchincontext AT stephenmdowns realworldeffectivenessandcausalmediationstudyofbnt162b2onlongcovidrisksinchildrenandadolescentsresearchincontext AT kathrynhirabayashi realworldeffectivenessandcausalmediationstudyofbnt162b2onlongcovidrisksinchildrenandadolescentsresearchincontext AT aarondmishkin realworldeffectivenessandcausalmediationstudyofbnt162b2onlongcovidrisksinchildrenandadolescentsresearchincontext AT abusmmosa realworldeffectivenessandcausalmediationstudyofbnt162b2onlongcovidrisksinchildrenandadolescentsresearchincontext AT nathanmpajor realworldeffectivenessandcausalmediationstudyofbnt162b2onlongcovidrisksinchildrenandadolescentsresearchincontext AT suchitrarao realworldeffectivenessandcausalmediationstudyofbnt162b2onlongcovidrisksinchildrenandadolescentsresearchincontext AT haniehrazzaghi realworldeffectivenessandcausalmediationstudyofbnt162b2onlongcovidrisksinchildrenandadolescentsresearchincontext AT haydentschwenk realworldeffectivenessandcausalmediationstudyofbnt162b2onlongcovidrisksinchildrenandadolescentsresearchincontext AT marionrsills realworldeffectivenessandcausalmediationstudyofbnt162b2onlongcovidrisksinchildrenandadolescentsresearchincontext AT huiyuanwang realworldeffectivenessandcausalmediationstudyofbnt162b2onlongcovidrisksinchildrenandadolescentsresearchincontext AT linbowang realworldeffectivenessandcausalmediationstudyofbnt162b2onlongcovidrisksinchildrenandadolescentsresearchincontext AT yudongwang realworldeffectivenessandcausalmediationstudyofbnt162b2onlongcovidrisksinchildrenandadolescentsresearchincontext AT dazhengzhang realworldeffectivenessandcausalmediationstudyofbnt162b2onlongcovidrisksinchildrenandadolescentsresearchincontext AT tingzhou realworldeffectivenessandcausalmediationstudyofbnt162b2onlongcovidrisksinchildrenandadolescentsresearchincontext AT ravijhaveri realworldeffectivenessandcausalmediationstudyofbnt162b2onlongcovidrisksinchildrenandadolescentsresearchincontext AT ericjtchetgentchetgen realworldeffectivenessandcausalmediationstudyofbnt162b2onlongcovidrisksinchildrenandadolescentsresearchincontext AT jeffreysmorris realworldeffectivenessandcausalmediationstudyofbnt162b2onlongcovidrisksinchildrenandadolescentsresearchincontext AT christopherbforrest realworldeffectivenessandcausalmediationstudyofbnt162b2onlongcovidrisksinchildrenandadolescentsresearchincontext AT yongchen realworldeffectivenessandcausalmediationstudyofbnt162b2onlongcovidrisksinchildrenandadolescentsresearchincontext |