The respiratory microbiome is linked to severity of RSV infections and persistence of symptoms in children

Respiratory syncytial virus (RSV) is the leading cause of infant respiratory infections and hospitalizations. To investigate the relationship between the respiratory microbiome and RSV infection, we sequence nasopharyngeal samples from a birth cohort and pediatric case-control study (RESCEU consortium). 1537 samples are collected shortly after birth (‘baseline’), during RSV infection and convalescence, and from healthy controls. We find a modest association between baseline microbiota and severity of consecutive RSV infections. The respiratory microbiota during infection clearly differs between infants with RSV and controls. Haemophilus, Streptococcus and Moraxella abundance are associated with severe disease and persistence of symptoms, whereas stepwise increasing abundance of Dolosigranulum and Corynebacterium is associated with milder disease and health. We conclude that the neonatal respiratory microbiota is only modestly associated with RSV severity during the first year of life. However, the respiratory microbiota at time of infection is strongly associated with disease severity and residual symptoms.