Enhanced Neutralizing Antibody Responses to Rhinovirus C and Age-Dependent Patterns of Infection

program collaborators for Environmental influences on Child Health Outcomes

Research output: Contribution to journalArticlepeer-review

22 Scopus citations


RATIONALE: Rhinovirus C (RV-C) can cause asymptomatic infection and respiratory illnesses ranging from the common cold to severe wheezing.

OBJECTIVES: To identify how age and other individual-level factors are associated with susceptibility to RV-C illnesses.

METHODS: Longitudinal data from the Childhood Origins of ASThma (COAST) birth cohort study were analyzed to determine relationships between age and RV-C infections. Neutralizing antibodies specific for rhinovirus A (RV-A) and RV-C (3 types each) were determined using a novel polymerase chain reaction-based assay. We pooled data from 14 study cohorts in the United States, Finland, and Australia and used mixed-effects logistic regression to identify factors related to the proportion of RV-C versus RV-A detection.

MEASUREMENTS AND MAIN RESULTS: In COAST, RV-A and RV-C infections were similarly common in infancy, while RV-C was detected much less often than RV-A during both respiratory illnesses and scheduled surveillance visits (p<0.001, chi-square) in older children. The prevalence of neutralizing antibodies to RV-A or RV-C types was low (5%-27%) at age 2 years, but by age 16, RV-C seropositivity was more prevalent (78% vs. 18% for RV-A, p<0.0001). In the pooled analysis, the RV-C to RV-A detection ratio during illnesses was significantly related to age (p<0.0001), CDHR3 genotype (p<0.05), and wheezing illnesses (p<0.05). Furthermore, certain RV types (e.g., C2, C11, A78, A12) were consistently more virulent and prevalent over time.

DISCUSSION: Knowledge of prevalent RV types, antibody responses, and populations at risk based on age and genetics may guide the development of vaccines or other novel therapies against this important respiratory pathogen.

Original languageEnglish (US)
Pages (from-to)822-830
Number of pages9
JournalAmerican journal of respiratory and critical care medicine
Issue number7
Early online dateDec 24 2020
StatePublished - Apr 1 2021

Bibliographical note

Funding Information:
Supported by the Environmental Influences on Child Health Outcomes program, Office of The Director, NIH, under award numbers U2COD023375 (Coordinating Center), U24OD023382 (Data Analysis Center), U24OD023319 (Person-Reported Outcome [PRO] Core), UG3/UH3 OD023282, and UG3/UH3 OD-023253; NIH grants R01AI148707, P01 HL070831, UM1 AI114271, R01 AI-114552, R01 AI-127507, U19 AI095227, UL1 RR024975, and R01-AI097172; the Sigrid Juselius Foundation, Helsinki, Finland; National Health and Medical Research Council grants 211912, 458513; and by grants APP1045760, APP1087700, APP1129996, APP1147630. The content is solely the responsibility of the authors and does not necessarily represent the official views of the NIH and other funding agencies.

Publisher Copyright:
© 2021 by the American Thoracic Society.


  • CDHR3
  • Epidemiology
  • Genetics
  • Rhinovirus
  • Wheezing
  • Age Factors
  • Rhinovirus/genetics
  • Humans
  • Australia/epidemiology
  • Child, Preschool
  • Infant
  • Male
  • Genetic Variation
  • Picornaviridae Infections/epidemiology
  • United States/epidemiology
  • Female
  • Child
  • Infant, Newborn
  • Disease Susceptibility
  • Respiratory Sounds/physiopathology
  • Genotype
  • Antibodies, Neutralizing/blood
  • Finland/epidemiology
  • Adolescent
  • Asthma/epidemiology
  • Longitudinal Studies
  • Cohort Studies

PubMed: MeSH publication types

  • Research Support, Non-U.S. Gov't
  • Research Support, U.S. Gov't, P.H.S.
  • Journal Article
  • Research Support, N.I.H., Extramural
  • Comparative Study


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