Type-III Interferons, Viral Loads, Age, and Disease Severity in Young Children with Respiratory Syncytial Virus Infection

Abstract Background The interplay among 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; > 6-24 months) and multivariable analyses performed to identify predictors of disease severity. Results From 2015-2019 we enrolled 219 RSV-infected children (78 outpatients; 141 inpatients) and 34 healthy controls. Type I, II, III IFN concentrations were higher in children >6 vs 0-6 months and like CXCL10 they were higher in outpatients than inpatients and correlated with RSV loads (p < 0.05). Higher IL6 concentrations increased the odds of hospitalization (OR, 95% CI; 2.30 [1.07-5.36]) only in children >6 months, while higher IFNL2/IFNL3 concentrations had the opposite effect irrespective of age (0.38 [0.15-0.86]). Likewise, higher CXCL10 concentrations decreased the odds of hospitalization (0.21 [0.08-0.48]), oxygen administration (0.42 [0.21-0.80]), PICU (0.39 [0.20-0.73]), and prolonged hospitalization (0.57 [0.32-0.98]) irrespective of age. Conclusions Children with milder RSV infection and those >6 months had higher concentrations of mucosal IFNs, suggesting that maturation of mucosal IFN responses are associated with protection against severe RSV disease.