Type III Interferons, Viral Loads, Age, and Disease Severity in Young Children With Respiratory Syncytial Virus Infection
Author:
Taveras Jeanette1, Garcia-Maurino Cristina2, Moore-Clingenpeel Melissa3, Xu Zhaohui2, Mertz Sara2, Ye Fang2, Chen Phyl2, Cohen Shira H2, Cohen Daniel4, Peeples Mark E2, Ramilo Octavio12, Mejias Asuncion12ORCID
Affiliation:
1. Department of Pediatrics, Division of Infectious Diseases, Nationwide Children's Hospital and The Ohio State College of Medicine , Columbus, Ohio , USA 2. Center for Vaccines and Immunity, Abigail Wexner Research Institute at Nationwide Children's Hospital, The Ohio State College of Medicine , Columbus, Ohio , USA 3. Biostatistics Core, Abigail Wexner Research Institute at Nationwide Children's Hospital , Columbus, Ohio , USA 4. Department of Pediatrics, Division of Emergency Medicine at Nationwide Children's Hospital and The Ohio State University College of Medicine , Columbus, Ohio , USA
Abstract
Abstract
Background
The interplay among respiratory syncytial virus (RSV) loads, mucosal interferons (IFN), and disease severity in RSV-infected children is poorly understood.
Methods
Children <2 years of age with mild (outpatients) or severe (inpatients) RSV infection and healthy controls were enrolled, and nasopharyngeal samples obtained for RSV loads and innate cytokines quantification. Patients were stratified by age (0–6 and >6–24 months) and multivariable analyses performed to identify predictors of disease severity.
Results
In 2015–2019 we enrolled 219 RSV-infected children (78 outpatients; 141 inpatients) and 34 healthy controls. Type I, II, and III IFN concentrations were higher in children aged >6 versus 0–6 months and, like CXCL10, they were higher in outpatients than inpatients and correlated with RSV loads (P < .05). Higher IL6 concentrations increased the odds of hospitalization (odds ratio [OR], 2.30; 95% confidence interval [CI], 1.07–5.36) only in children >6 months, while higher IFN-λ2/3 concentrations had the opposite effect irrespective of age (OR, 0.38; 95% CI, .15–.86). Likewise, higher CXCL10 concentrations decreased the odds of hospitalization (OR, 0.21; 95% CI, .08–.48), oxygen administration (OR, 0.42; 95% CI, .21–.80),PICU admission (OR, 0.39; 95% CI, .20–.73), and prolonged hospitalization (OR, 0.57; 95% CI, .32–.98) irrespective of age.
Conclusions
Children with milder RSV infection and those aged >6 months had higher concentrations of mucosal IFNs, suggesting that maturation of mucosal IFN responses are associated with protection against severe RSV disease.
Funder
National Institutes of Health Janssen
Publisher
Oxford University Press (OUP)
Subject
Infectious Diseases,Immunology and Allergy
Reference46 articles.
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