Immune correlates of risk for SARS-CoV-2 infection in children: a prospective, community-based cohort study

Few studies have characterized immune correlates of SARS-CoV-2 infection risk in children, particularly those with hybrid immunity from vaccination and prior infection. We conduct a prospective community-based cohort study of 1509 U.S. children (2022–2024), performing weekly SARS-CoV-2 PCR testing and measuring baseline binding and neutralizing antibody titers against multiple variants. Higher antibody levels, notably nucleocapsid-binding and Omicron-specific neutralizing antibodies, are significantly associated with reduced risk of SARS-CoV-2 infection after adjusting for age, recent infection, exposure settings, and temporal trends (adjusted hazard ratios ranging from 0.60 to 0.87 per positive unit difference in log10-fold antibody level (AU/mL)). Secondary analyses suggest these findings are robust to multiple stratifications of SARS-CoV-2 immune status, are relevant across different pediatric age groups, and appear to apply to both overall and symptomatic infection risk. Together, the results suggest that specific antibodies can predict relative infection risk in pediatric populations with diverse immune histories. Understanding these immune correlates may inform tailored vaccination strategies and risk assessments as SARS-CoV-2 continues to evolve. Understanding immune correlates of SARS-CoV-2 infection risk in children, especially those with hybrid immunity, remains underexplored. Here, the authors conduct a cohort study revealing that higher nucleocapsid-binding and Omicron-specific neutralizing antibodies significantly reduce infection risk, suggesting these markers could guide tailored vaccination strategies and risk assessments in pediatric populations.

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Publication Details

Journal
Nature Communications
Published
2026-07-18
DOI
https://doi.org/10.1038/s41467-026-74684-8
Primary Topic
COVID-19 Clinical Research Studies
Type
article
Field-Weighted Citation Impact
0.00

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Immune correlates of risk for SARS-CoV-2 infection in children: a prospective, community-based cohort study

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Immune correlates of risk for SARS-CoV-2 infection in children: a prospective, community-based cohort study

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article en

Abstract

Few studies have characterized immune correlates of SARS-CoV-2 infection risk in children, particularly those with hybrid immunity from vaccination and prior infection. We conduct a prospective community-based cohort study of 1509 U.S. children (2022–2024), performing weekly SARS-CoV-2 PCR testing and measuring baseline binding and neutralizing antibody titers against multiple variants. Higher antibody levels, notably nucleocapsid-binding and Omicron-specific neutralizing antibodies, are significantly associated with reduced risk of SARS-CoV-2 infection after adjusting for age, recent infection, exposure settings, and temporal trends (adjusted hazard ratios ranging from 0.60 to 0.87 per positive unit difference in log10-fold antibody level (AU/mL)). Secondary analyses suggest these findings are robust to multiple stratifications of SARS-CoV-2 immune status, are relevant across different pediatric age groups, and appear to apply to both overall and symptomatic infection risk. Together, the results suggest that specific antibodies can predict relative infection risk in pediatric populations with diverse immune histories. Understanding these immune correlates may inform tailored vaccination strategies and risk assessments as SARS-CoV-2 continues to evolve. Understanding immune correlates of SARS-CoV-2 infection risk in children, especially those with hybrid immunity, remains underexplored. Here, the authors conduct a cohort study revealing that higher nucleocapsid-binding and Omicron-specific neutralizing antibodies significantly reduce infection risk, suggesting these markers could guide tailored vaccination strategies and risk assessments in pediatric populations.

Nature Communications
Centers for Disease Control and Prevention (US), University of Washington (US), Fred Hutch Cancer Center (US), Kaiser Permanente Center for Health Research (US), Brotman Baty Institute (US), University of Pennsylvania (US)
Centers for Disease Control and Prevention
Openalex Percentile: Top 8%
COVID-19 Clinical Research Studies
DOIOpen Access PDFOpenAlex
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