Abstract
RATIONALE: Respiratory syncytial virus (RSV) bronchiolitis is a major cause of morbidity and mortality in infancy. Severe disease is believed to result from uncontrolled viral replication, an excessive immune response, or both. OBJECTIVES: To determine RSV load and immune mediator levels in nasal mucosal lining fluid by serial sampling of nasal fluids from cases of moderate and severe bronchiolitis over the course of infection. METHODS: Infants with viral bronchiolitis necessitating admission (n = 55) were recruited from a pediatric center during 2016 and 2017. Of these, 30 were RSV infected (18 "moderate" and 12 mechanically ventilated "severe"). Nasal fluids were sampled frequently over time using nasosorption devices and nasopharyngeal aspiration. Hierarchical clustering of time-weighted averages was performed to investigate cytokine and chemokine levels, and gene expression profiling was conducted. MEASUREMENTS AND MAIN RESULTS: Unexpectedly, cases with severe RSV bronchiolitis had lower nasal viral loads and reduced IFN-γ and C-C chemokine ligand 5/RANTES (regulated upon activation, normal T cell expressed and secreted) levels than those with moderate disease, especially when allowance was made for disease duration (all P < 0.05). Reduced cytokine/chemokine levels in severe disease were also seen in children with other viral infections. Gene expression analysis of nasopharyngeal aspiration samples (n = 43) confirmed reduced type-I IFN gene expression in severe bronchiolitis accompanied by enhanced expression of MUC5AC and IL17A. CONCLUSIONS: Infants with severe RSV bronchiolitis have lower nasal viral load, CXCL10 (C-X-C motif chemokine ligand 10)/IP-10, and type-I IFN levels than moderately ill children, but enhanced MUC5AC (mucin-5AC) and IL17A gene expression in nasal cells.