Optimizing the sensitivity of detection of respiratory syncytial virus infections in longitudinal studies using the combination of weekly sample testing and biannual serology.

Creator(s)

• Shannon C. Conrey
• Daniel C. Payne
• Maria Deza Leon, Children's Mercy Kansas CityFollow
• Monica Epperson
• Melissa M. Coughlin
• Allison R. Burrell
• Claire P. Mattison
• Rachel M. Burke
• Julia M. Baker
• Natalie J. Thornburg
• Meredith L. McMorrow
• Mary Allen Staat
• Ardythe L. Morrow

Document Type

Article

Publication Date

6-3-2026

Identifier

DOI: 10.1093/aje/kwaf271; PMCID: PMC12767786

Abstract

Cohort studies are often challenged by incomplete adherence to sampling regimens, limiting the full capture of disease burden. We describe the detection of respiratory syncytial virus (RSV) infections achieved in a birth cohort using a combination of weekly nasal sample testing and serology. The Pediatric Respiratory and Enteric Viral Acquisition and Immunogenesis Longitudinal Cohort followed 245 maternal-child dyads from birth to age 18 to 24 months. Weekly mid-turbinate nasal swabs were tested for RSV using real-time polymerase chain reaction (RT-qPCR). Serum was tested for RSV pre-fusion F IgG and IgA antibody at age 6 weeks and biannually from 6 to 24 months. Mixed effects classification and regression trees identified antibody thresholds consistent with a RT-qPCR-identified RSV infection using a subset of participants having ≥90% weekly sample adherence (n = 53, 21%). Resulting thresholds were applied to participants with either ≥70% of weekly samples or serum at age 18 to 24 months (n = 194, 79%). Incidence rates were compared using Fisher's exact test. Classification and regression trees identified a log10 change in IgG > 0.32 or IgA > 0.20 as indicative of an RSV infection. Comparing RT-qPCR-only to a combination of RT-qPCR and serology, RSV cumulative incidence (49% vs 75%, P <  .001) and incidence rate (0.33 vs 0.71 infections/child-year, P <  .001) increased; these rates did not differ from those calculated in those with ≥90% sample adherence.

Journal Title

American journal of epidemiology

Volume

195

Issue

6

First Page

1605

Last Page

1614

MeSH Keywords

Humans; Respiratory Syncytial Virus Infections; Longitudinal Studies; Infant; Female; Sensitivity and Specificity; Antibodies, Viral; Child, Preschool; Male; Infant, Newborn; Immunoglobulin G; Real-Time Polymerase Chain Reaction; Immunoglobulin A; Birth Cohort

PubMed ID

41360520

Keywords

attrition bias; cohort studies; decision trees; epidemiologic methods; incidence rate; infectious disease epidemiology; misclassification bias; selection bias

Comments

Grants and funding

• UM1 TR005265/TR/NCATS NIH HHS/United States
• U01 AI144673/AI/NIAID NIH HHS/United States
• UL1 TR001425/TR/NCATS NIH HHS/United States
• T32 ES010957/ES/NIEHS NIH HHS/United States
• R01 HD109915/HD/NICHD NIH HHS/United States
• R01HD109915/MOM2CHild study
• U01A1144673/IMPRINT Cohort
• UL1TR001425/National Center for Advancing Translational Sciences of the National Institutes of Health
• 5 T32 ES 10957-18/Molecular Epidemiology in Children's Environmental Health Training program
• IP16-004/US Centers for Disease Control and Prevention

This is an open access article distributed under the terms of the Creative Commons CC BY license, which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.

Publisher's Link: https://academic.oup.com/aje/article/195/6/1605/8374243

Recommended Citation

Conrey SC, Payne DC, Leon MD, et al. Optimizing the sensitivity of detection of respiratory syncytial virus infections in longitudinal studies using the combination of weekly sample testing and biannual serology. Am J Epidemiol. 2026;195(6):1605-1614. doi:10.1093/aje/kwaf271