Abstract
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.
| Original language | English (US) |
|---|---|
| Article number | 102962 |
| Journal | EClinicalMedicine |
| Volume | 79 |
| DOIs | |
| State | Published - Jan 2025 |
Funding
National Institutes of Health.This work was supported in part by National Institutes of Health (OT2HL161847-01, 1R01LM012607, 1R01AI130460, 1R01AG073435, 1R56AG074604, 1R01LM013519, 1R01LM014344, 1R56AG069880, 1R01AG077820, 1U01TR003709, 1R21AI167418, 1R21EY034179). This work was supported partially through Patient-Centered Outcomes Research Institute (PCORI) Project Program Awards (ME-2019C3-18315 and ME-2018C3-14899). All statements in this report, including its findings and conclusions, are solely those of the authors and do not necessarily represent the views of the Patient-Centered Outcomes Research Institute (PCORI), its Board of Governors, or Methodology Committee. This content is solely the responsibility of the authors and does not necessarily represent the official views of the RECOVER Initiative, the NIH, or other funders. Reference NIH Involvement:, This study is part of the NIH Researching COVID to Enhance Recovery (RECOVER) Initiative, which seeks to understand, treat, and prevent the post-acute sequelae of SARS-CoV-2 infection (PASC). For more information on RECOVER, visit https://recovercovid.org/. Representative Acknowledgement:, We would like to thank the National Community Engagement Group (NCEG), all patients, caregivers, and community representatives, and all the participants enrolled in the RECOVER Initiative. We also would like to thank Drs. Margot I. Gage Witvliet and Megan L. Fitzgerald for their helpful discussions. This work was supported in part by National Institutes of Health (OT2HL161847-01, 1R01LM012607, 1R01AI130460, 1R01AG073435, 1R56AG074604, 1R01LM013519, 1R01LM014344, 1R56AG069880, 1R01AG077820, 1U01TR003709, 1R21AI167418, 1R21EY034179). This work was supported partially through Patient-Centered Outcomes Research Institute (PCORI) Project Program Awards (ME-2019C3-18315 and ME-2018C3-14899). All statements in this report, including its findings and conclusions, are solely those of the authors and do not necessarily represent the views of the Patient-Centered Outcomes Research Institute (PCORI), its Board of Governors, or Methodology Committee.
Keywords
- Causal mediation analysis
- Long COVID
- Pediatric research
- Real-world effectiveness
- Vaccination
ASJC Scopus subject areas
- General Medicine
