Pfizer-BioNTech Vaccine Cuts Long COVID Risk by Up to 20x in Children

A study by researchers at the University of Pennsylvania's Perelman School of Medicine found that the Pfizer-BioNTech COVID-19 vaccine protects children and adolescents from Long COVID by preventing initial infections. Analyzing nearly 400,000 pediatric records, the study, published in The Lancet eClinicalMedicine, compared vaccinated versus unvaccinated children and adolescents during the Delta and Omicron waves. The results showed that unvaccinated children were up to 20 times more likely to develop Long COVID than those vaccinated.¹

Delta Variant (July-November 2021)²

• The vaccine was 95.4% effective in preventing Long COVID in adolescents aged 12-20. Vaccinated adolescents had .11 cases of Long COVID per 10,000 person-weeks, compared to 3.54 cases in the unvaccinated group, a 32-fold difference.

Omicron Variant (January-November 2022)²

• For children aged 5-11, the vaccine was 60.2% effective, reducing the incidence from 1.07 in unvaccinated children to .33 in vaccinated children.
• For adolescents aged 12-20, the vaccine was 75.1% effective, reducing the incidence from 1.43 in unvaccinated adolescents to .24 in vaccinated adolescents.

According to the investigators, “This is the first study of the impact of COVID-19 vaccines on Long COVID outcomes that offers insights into both the overall vaccine effectiveness and effects through distinct mediating pathways.”²

Causal mediation analysis showed that the vaccine's primary benefit was preventing initial SARS-CoV-2 infections. Once infected, vaccinated children and adolescents had similar Long COVID risks as unvaccinated peers, indicating the vaccine’s role in infection prevention rather than reducing post-acute sequelae of SARS-CoV-2 (PASC).²

The study included 112,590 adolescents aged 12-20 during the Delta phase (88,811 vaccinated) and 188,894 children aged 5-11, and 84,735 adolescents aged 12-20 during the Omicron phase (101,277 children and 37,724 adolescents vaccinated).²

The study has several limitations, including potential bias from undocumented infections, reduced generalizability due to late vaccinations in adolescents, limited follow-up time for some cohorts, incomplete vaccine records for individuals outside network sites, and challenges in identifying Long COVID in children using EHR data. Additionally, an updated analysis is needed to assess the findings in the context of current variants.²

In another recent study evaluating children and adolescents with SARS-CoV-2 infection, it was found that these individuals were more likely to develop myocarditis, heart failure, arrhythmias, and chest pain, regardless of prior cardiovascular history or congenital heart disease (CHD). This study, also part of the RECOVER initiative, highlighted that increased cardiovascular risks were consistent across various demographics, including age, sex, race/ethnicity, and COVID-19 severity. Even healthy children without previous heart conditions showed an elevated risk for post-acute cardiovascular outcomes after contracting COVID-19.³

In conclusion, this study shows that the Pfizer-BioNTech COVID-19 vaccine helps protect children and adolescents from Long COVID by preventing initial infections. Unvaccinated children and adolescents were up to 20 times more likely to develop Long COVID compared to vaccinated individuals.

References

1. University of Pennsylvania School of Medicine. COVID vaccine protected kids from long COVID. EurekAlert! News release. April 21, 2025. Accessed April 21, 2025. https://www.eurekalert.org/news-releases/1081173

2. Wu Q, Zhang B, Tong J, et al. Real-world effectiveness and causal mediation study of BNT162b2 on long COVID risks in children and adolescents. EClinicalMedicine. 2025;79:102962. doi:10.1016/j.eclinm.2024.102962

3. Zhang, B., Thacker, D., Zhou, T. et al. Cardiovascular post-acute sequelae of SARS-CoV-2 in children and adolescents: cohort study using electronic health records. Nat Commun 16, 3445 (2025). https://doi.org/10.1038/s41467-025-56284-0