Infant RSV prophylaxis, RSV infection, and nasopharyngeal microbiota at age six years

Background: Respiratory syncytial virus (RSV) infection during infancy is suggested to cause long-term wheeze. In turn, wheeze has been associated with bacterial dysbiosis of the respiratory tract. We investigated the effects of RSV prophylaxis by palivizumab during infancy on respiratory microbiota composition at six years of age in participants of an RCT. Methods: 429 infants born between 32-35 weeks of gestation randomly received palivizumab or placebo during the RSV season of their first year of life. Children were followed for clinical symptoms until 6 years of age. At age six, nasopharyngeal swabs were collected and reversible airway obstruction was determined. Samples of 395 children were available for 16S-rRNA sequencing. Findings: We observed that RSV prophylaxis in infancy was associated with a higher abundance of Haemophilus and lower abundance of Moraxella and Neisseria, at age six years. Stratified analysis comparing microbiota at age six of children with PCR-confirmed RSV infection to children without proven RSV infection in infancy showed similar microbiota associations compared to those found with RSV prophylaxis. PCR-confirmed rhinovirus infection in infancy partly negated the impact of PCR-confirmed RSV infection on respiratory microbiota at age six. Reversible airway obstruction at age six was positively associated with Haemophilus and Streptococcus abundance and negatively associated with the abundance of health-associated spp., e.g. Moraxella, Neisseria, Corynebacterium and Dolosigranulum. Interpretation: Together, our results warrant further studies to shed light on the long-term ecological effects of viral infections and (RSV) prophylaxis in infancy.