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

The effectiveness of COVID-19 vaccination in children and adolescents with prior SARS-CoV-2 infection remains unclear, particularly for Omicron subvariants. We evaluate vaccine effectiveness against reinfection with Omicron BA.1/BA.2, BA.4/BA.5, XBB, and later subvariants among 5- to 17-year-olds using data from the RECOVER initiative, a national electronic health record database covering 37 U.S. children's hospitals and health institutions. We emulate target trials by age group and variant period, comparing previously infected participants between January 2022 and August 2023. During the BA.1/BA.2 period, vaccination reduces the risk of reinfection, with effectiveness rates of 62% in children and 65% in adolescents. During the BA.4/BA.5 period, protection effectiveness in children was 57%, whereas no statistically significant protection is observed in adolescents. During the XBB and later period, no significant protection is observed in either group. In summary, COVID-19 vaccination provides protection against reinfection during the early and mid-Omicron periods in previously infected pediatric populations, but effectiveness declines for later variants.

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Publication Details

Journal
Nature Communications
Published
2026-04-17
DOI
https://doi.org/10.1038/s41467-026-71820-2
Primary Topic
SARS-CoV-2 and COVID-19 Research
Type
article
Field-Weighted Citation Impact
0.00

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article

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

Srinivasan Suresh, Christopher B. Forrest, Alice I. Sato, Yongqun He et al.
Nature Communications
SARS-CoV-2 and COVID-19 Research
article

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

Srinivasan Suresh, Christopher B. Forrest, Alice I. Sato, Yongqun He, Hayden T. Schwenk, Ravi R. Jhaveri, Daniel Fort, Abu Saleh Mohammad Mosa, Sandy L. Gonzalez, Parsa Mirhaji, Bradley Taylor, Jennifer A. Muszynski, Yuriy Bisyuk, Sharon J. Herring, Mollie Cummins, Catharine I. Paules, Benjamin D. Horne, Michael J. Becich, Lindsay G. Cowell, Yong Chen, Soumitra SenGupta, Ting Zhou, Jeffrey S. Morris, Soledad Fernández, Saul Blecker, Dimitri A. Christakis, Susan Kim, Mei Hong Liu, Elizabeth A. Chrischilles, Qiong Wu, Carol Horowitz, Bingyu Zhang, David A. Williams, Jiajie Chen, Yuqing Lei
article en

Abstract

The effectiveness of COVID-19 vaccination in children and adolescents with prior SARS-CoV-2 infection remains unclear, particularly for Omicron subvariants. We evaluate vaccine effectiveness against reinfection with Omicron BA.1/BA.2, BA.4/BA.5, XBB, and later subvariants among 5- to 17-year-olds using data from the RECOVER initiative, a national electronic health record database covering 37 U.S. children's hospitals and health institutions. We emulate target trials by age group and variant period, comparing previously infected participants between January 2022 and August 2023. During the BA.1/BA.2 period, vaccination reduces the risk of reinfection, with effectiveness rates of 62% in children and 65% in adolescents. During the BA.4/BA.5 period, protection effectiveness in children was 57%, whereas no statistically significant protection is observed in adolescents. During the XBB and later period, no significant protection is observed in either group. In summary, COVID-19 vaccination provides protection against reinfection during the early and mid-Omicron periods in previously infected pediatric populations, but effectiveness declines for later variants.

Nature Communications
University of Nebraska–Lincoln (US), University of Nebraska at Omaha (US), University of Iowa (US), Lurie Children's Hospital (US), Seattle Children's Hospital (US), Albert Einstein College of Medicine (US), Nationwide Children's Hospital (US), Children's Hospital of Philadelphia (US), Ochsner Health System (US), University of Pittsburgh (US), Medical College of Wisconsin (US), University of Utah (US), University of Michigan (US), University Medical Center New Orleans (US), University of the Arts (US), Intermountain Medical Center (US), University of Alabama at Birmingham (US), University of Florida (US), Southwestern Medical Center (US), Department of Health (TW), Penn Center for AIDS Research (US), Children's Hospital of Pittsburgh (US), Applied Mathematics (United States) (US), UCSF Benioff Children's Hospital (US), Stanford Medicine (US), University of Pennsylvania Health System (US), Miami Children's Hospital (US), Children's Hospital & Medical Center (US), The Ohio State University (US), New York University (US), University of Nebraska Medical Center (US), Columbia University (US), University of Pennsylvania (US), Penn State Milton S. Hershey Medical Center (US), Temple University (US), The University of Texas Southwestern Medical Center (US), Icahn School of Medicine at Mount Sinai (US)
Foundation for the National Institutes of Health, Patient-Centered Outcomes Research Institute, National Institutes of Health
Zero hunger
Openalex Percentile: Top 17%
SARS-CoV-2 and COVID-19 Research
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