Abstract
BACKGROUND: Respiratory viral infections are common and can trigger asthma exacerbations in children. The roles of the nasal microbiome and phageome (viruses that infect microbes) are not well understood.
OBJECTIVE: We sought to characterize the epidemiology of respiratory viral infections and the interplay between the nasal microbiome, phageome, and viral infections in school-age children with asthma.
METHODS: We performed metagenomic sequencing and quantitative RT-PCR detection of respiratory viruses on 375 nasal samples from 227 school-age children with asthma collected routinely 3 times over a year. Surveys on parent-reported cold and asthma symptoms were administered routinely every 2 months. We evaluated multikingdom changes to the nasal microbiome during infection. A sparse partial least-squares discriminant analysis model identified microbial signatures associated with prospective viral infection risk.
RESULTS: Respiratory viruses were identified in 124 (33%) samples, with rhinovirus being the most prevalent. Cold and asthma symptoms within the previous 14 days had a sensitivity of 79% and 59%, respectively, for quantitative RT-PCR-confirmed infection. Respiratory viral infection increased asthma symptoms and was accompanied by loss of nasal bacterial diversity and a reproducible bloom of pathobionts with no change in the mycobiome or phageome. A baseline bacteriome-dominated profile was protective (adjusted odds ratio, 0.41 [95% CI, 0.25-0.67]; P < .001), whereas phageome profiles increased risk (adjusted odds ratio, 3.74 [95% CI, 1.85-7.55]; P < .001) of viral infection. Specific phages inversely correlated with Staphylococcus epidermidis abundance, the most protective commensal against infection risk.
CONCLUSIONS: The nasal microbiome and phageome exert opposing influences on respiratory viral infection risk, highlighting their potential roles in modulating susceptibility to viral infections.