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

Katherine L Hoffman1, Grace Marshall2, Collrane Frivold2,3

  • 1Department of Biostatistics, University of Washington, Seattle, WA, USA. khof@uw.edu.

Nature Communications
|July 17, 2026
PubMed

Insights

Specific antibodies, like nucleocapsid-binding and Omicron-specific neutralizing antibodies, significantly reduce the risk of SARS-CoV-2 infection in children with hybrid immunity. These findings aid in assessing risk and tailoring vaccination strategies.

Area of Science:

  • Pediatric Immunology
  • Infectious Diseases
  • Virology

Background:

  • Limited data exists on immune markers predicting SARS-CoV-2 infection risk in children.
  • Understanding correlates is crucial for managing pediatric populations with hybrid immunity (vaccination + prior infection).

Purpose of the Study:

  • To identify specific antibody correlates associated with reduced SARS-CoV-2 infection risk in U.S. children.
  • To evaluate the predictive value of antibody titers in a pediatric cohort with diverse immune histories.

Main Methods:

  • Prospective community-based cohort study of 1509 U.S. children (2022-2024).
  • Weekly SARS-CoV-2 PCR testing and measurement of baseline binding and neutralizing antibody titers against multiple variants.
  • Statistical analysis adjusting for age, recent infection, exposure, and temporal trends.

Main Results:

  • Higher antibody levels, particularly nucleocapsid-binding and Omicron-specific neutralizing antibodies, were significantly associated with lower SARS-CoV-2 infection risk.
  • Adjusted hazard ratios indicated a protective effect (0.60 to 0.87 per log10-fold increase in antibody level).
  • Findings were robust across different pediatric age groups and immune statuses, predicting both overall and symptomatic infection risk.

Conclusions:

  • Specific antibody titers can predict relative SARS-CoV-2 infection risk in children with varied immune backgrounds.
  • These immune correlates may inform optimized vaccination strategies and risk stratification for pediatric populations.
  • Further understanding is vital as SARS-CoV-2 continues to evolve.

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