RSV disease severity is driven by greater suppression of the host immune response.

<p>(A) Modular fingerprints were independently derived from children with mild (<i>n</i> = 20), moderate (<i>n</i> = 17), or severe (<i>n</i> = 16) disease based on a CDSS, and from ten healthy controls. All RSV patients and controls were age and gender matched. Median (IQR) CDSS indicated for each disease severity group. (B) Horizontal bars illustrating the percentage of overexpressed, underexpressed, and unchanged modules compared to healthy controls for children with mild, moderate, and severe RSV LRTI (Chi square test <i>p</i> = 0.0025). (C and D) Significantly overexpressed (C) and underexpressed (D) modules in children with different degrees of clinical severity. Dots represent the median expression value for each individual transcript in all three disease severity groups (mild, moderate, and severe) per module or module aggregate sharing the same function. Genes related to interferon (M1.2, M3.4, M5.12) and innate immunity (M3.2, M4.2, M4.13) were significantly overexpressed in children with either moderate or severe RSV LRTI compared with children with mild disease. Overexpression of genes related to neutrophils (M5.15), inflammation (M4.6, M5.1, M6.13), and erythrocytes (M2.3, M3.1) significantly increased with disease severity. Children with severe RSV LRTI had significantly greater underexpression of genes related to T cells (M4.1, M4.15), cytotoxic/NK cells (M3.6), plasma cells (M4.11), cell cycle (M2.2, M3.3–5, M6.11–16), and mitochondrial metabolism (M5.10, M6.2, M6.12). Except for plasma cells, where adjusted (single asterisk) and unadjusted (double asterisk, in parentheses) <i>p</i>-values are displayed, all other <i>p</i>-values represent adjusted <i>p</i>-values (single asterisk) after applying the Bonferroni correction for multiple comparisons. N/S, not significant.