Research ArticleInfectious Disease

Immune profiles provide insights into respiratory syncytial virus disease severity in young children

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Science Translational Medicine  22 Apr 2020:
Vol. 12, Issue 540, eaaw0268
DOI: 10.1126/scitranslmed.aaw0268

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Understanding severity in RSV

Almost all young children become infected with respiratory syncytial virus (RSV), but only a small proportion progress to severe disease, and certain immune responses have been shown to be harmful. To better understand immune signatures associated with mild or severe disease, Heinonen et al. performed transcriptomic and flow cytometry analysis on samples from RSV-infected children under the age of two. Children had either severe (inpatients) or mild disease (outpatients). Severe disease samples showed reduced viral loads and type I interferon signatures, as well as the presence of HLA-DRlow monocytes. Overall, a robust innate immune response seemed indicative of a more favorable outcome.

Abstract

Respiratory syncytial virus (RSV) is associated with major morbidity in infants, although most cases result in mild disease. The pathogenesis of the disease is incompletely understood, especially the determining factors of disease severity. A better characterization of these factors may help with development of RSV vaccines and antivirals. Hence, identification of a “safe and protective” immunoprofile induced by natural RSV infection could be used as a as a surrogate of ideal vaccine-elicited responses in future clinical trials. In this study, we integrated blood transcriptional and cell immune profiling, RSV loads, and clinical data to identify factors associated with a mild disease phenotype in a cohort of 190 children <2 years of age. Children with mild disease (outpatients) showed higher RSV loads, greater induction of interferon (IFN) and plasma cell genes, and decreased expression of inflammation and neutrophil genes versus children with severe disease (inpatients). Additionally, only infants with severe disease had increased numbers of HLA-DRlow monocytes, not present in outpatients. Multivariable analyses confirmed that IFN overexpression was associated with decreased odds of hospitalization, whereas increased numbers of HLA-DRlow monocytes were associated with increased risk of hospitalization. These findings suggest that robust innate immune responses are associated with mild RSV infection in infants.

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