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

Year: 2026

Type: article

Abstract: The effectiveness of COVID-19 vaccination in children and adolescents with prior SARS-CoV-2 infection remains unclear, particularly for Omicron subvariants. We evaluated vaccine effectiveness against reinfection with Omicron BA.1/2, BA.4/5, 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. pediatric institutions. We emulated target trials by age group and variant period, comparing previously infected participants between January 2022 and August 2023. During the BA.1/2 period, vaccination reduced the risk of reinfection, with effectiveness rates of 62% in children and 65% in adolescents. During the BA.4/5 period, protection effectiveness in children was 57%, whereas no statistically significant protection was observed in adolescents. During the XBB or later period, no significant protection was observed in either group. In summary, COVID-19 vaccination provided protection against reinfection during early and mid-Omicron periods in previously infected pediatric populations, but effectiveness declined for later variants.

Source: Nature Communications

DOI: 10.1038/s41467-026-71820-2

Institutions: University of Pennsylvania, University of Pittsburgh, University Medical Center New Orleans, NYU Langone Health, New York University, University of Iowa, Seattle Children's Research Institute, The University of Texas Southwestern Medical Center, University of Utah, The Ohio State University, Ochsner Health System, Miami Children's Hospital, Temple University, Intermountain Medical Center, Icahn School of Medicine at Mount Sinai, University of Florida, University of California, San Francisco, Albert Einstein College of Medicine, University of Alabama at Birmingham, UAB Medicine, Nationwide Children's Hospital, Pennsylvania State University, Penn State Milton S. Hershey Medical Center, Stanford Medicine, Stanford University, Columbia University, Children's Hospital of Pittsburgh, Medical College of Wisconsin, University of Michigan, Lurie Children's Hospital, Children's Hospital of Philadelphia, University of Pennsylvania Health System

Language: English

Topic: SARS-CoV-2 and COVID-19 Research

Subfield: Infectious Diseases

Field: Medicine

Domain: Health Sciences

SDG: Good health and well-being

Open Access status: gold

Estimated APC paid: $6,990

Funders: Foundation for the National Institutes of Health, AstraZeneca, Gilead Sciences, Pediatric Infectious Diseases Society, Patient-Centered Outcomes Research Institute, Seqirus, National Institutes of Health, National Institute on Aging, National Heart, Lung, and Blood Institute, National Institute of Allergy and Infectious Diseases, National Institute of Diabetes and Digestive and Kidney Diseases

Awards: G3537173503, Methods for Estimating Disease Burden of Seasonal Influenza, G5316515788, AI-ADRD: Accelerating interventions of AD/ADRD via Machine learning methods, G5514976981, G6690217060, Surrogate Augmented Deep Predictive Learning for Retinopathy of Prematurity, Coordinating Individually Measured Phenotypes to Advance Mental Health Research, G9000027382, G9000053926, G9000264030, Novel evidence-accumulation-driven methods for characterizing kidney stone progression, PANDA-MSD: Predictive Analytics via Networked Distributed Algorithms for Multi-System Diseases, TRiPOD: Toward Reusable Phenotypes in Observational Data for AD/ADRD - managing definitions and correcting bias, OTA-21-015A Post-Acute Sequelae of SARS-CoV-2 Infection Initiative: NYU Langone Health Clinical Science Core, Data Resource Core, and PASC Biorepository Core

OpenAlex ID: W7154716265