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Updated: Apr 19, 2026

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Target Trial Emulation of Vaccine Effectiveness in 5- to 17-years-olds with Prior SARS-CoV-2 Infection

Yuqing Lei1,2, Jiajie Chen1,2, Qiong Wu1,2,3

  • 1Department of Biostatistics, Epidemiology, and Informatics, University of Pennsylvania Perelman School of Medicine, Philadelphia, PA, USA.

Nature Communications
|April 17, 2026
PubMed

Insights

COVID-19 vaccination offers protection against reinfection in previously infected children and adolescents during early Omicron waves. However, vaccine effectiveness wanes against later Omicron subvariants like XBB.

Area of Science:

  • Immunology
  • Infectious Diseases
  • Pediatrics

Background:

  • The effectiveness of COVID-19 vaccination in pediatric populations previously infected with SARS-CoV-2 is not well-established, especially against emerging Omicron subvariants.
  • Understanding vaccine effectiveness is crucial for guiding public health strategies in children and adolescents.

Purpose of the Study:

  • To evaluate the effectiveness of COVID-19 vaccination against SARS-CoV-2 reinfection in previously infected children and adolescents (5-17 years).
  • To assess vaccine effectiveness across different Omicron subvariant periods (BA.1/BA.2, BA.4/BA.5, XBB and later).

Main Methods:

  • Utilized data from the RECOVER initiative, a national electronic health record database from 37 U.S. children's hospitals.
  • Emulated target trials comparing previously infected individuals by age group and variant period from January 2022 to August 2023.
  • Analyzed vaccine effectiveness against reinfection with specific Omicron subvariants.

Main Results:

  • During the BA.1/BA.2 period, vaccine effectiveness against reinfection was 62% in children and 65% in adolescents.
  • During the BA.4/BA.5 period, effectiveness was 57% in children, with no significant protection observed in adolescents.
  • No statistically significant protection against reinfection was observed for the XBB and later subvariant period in either group.

Conclusions:

  • COVID-19 vaccination provides protection against reinfection in previously infected pediatric populations during the early and mid-Omicron waves.
  • Vaccine effectiveness against reinfection declines significantly with later Omicron subvariants, highlighting the need for updated vaccine strategies.

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