Whole blood transcriptomics in RSV infected children

The objective of this study was to identify gene expression markers of disease severity in a cohort of RSV infected children Respiratory syncytial virus (RSV) is the number one pathogen causing lower respiratory tract infection that leads to hospitalization in young children. Despite growing insights in the disease pathogenesis, the clinical presentation in these children is highly variable and heterogeneous, and reliable markers predictive of disease progression are lacking. We characterized the host response to acute RSV infection to identify biomarkers associated with RSV disease and disease severity. Whole genome transcriptome was analysed early on the disease course in blood samples from otherwise healthy children <2 years of age, who were either hospitalized (n = 110) or evaluated as outpatients (n = 37) due to RSV infection. Age-matched non-RSV-infected healthy children (n = 51) were analysed in parallel. A clustering approach on the transcriptome data revealed biologically meaningful biomarkers associated with progression to severe RSV disease. Overall, the whole blood transcriptome pointed to alterations in frequency of specific immune cell types (neutrophils, T- and B-lymphocytes, NK cells, monocytes) in RSV-infected children. In addition, a cluster enriched for neutrophil degranulation genes, was highly correlated with clinical disease severity. The driver genes of this cluster (OLFM4, ELANE, MMP8, BPI, CEACAM8, LCN2, LTF and MPO) were selected and validated in independent existing transcriptomics datasets. We identified a set of genes involved in neutrophil degranulation as markers for RSV disease severity. Additional prospective studies using these markers are required to further confirm their value as predictive tool in routine clinical care. Blood samples for transcriptome analysis were collected at presentation from 37 outpatients and 110 inpatients. Follow-up blood samples were collected 30 and 180 days later from 86 and 69 of the patients, respectively. In addition, a cohort of 51 healthy children were enrolled and a blood sample was collected.