Abstract
BACKGROUND: Bronchiolitis is a leading cause of infant hospitalization. Recent research suggests the heterogeneity within bronchiolitis and the relationship of airway viruses and bacteria with bronchiolitis severity. However, little is known about the pathobiological role of fungi. We aimed to identify bronchiolitis mycotypes by integrating fungus and virus data, and determine their association with bronchiolitis severity and biological characteristics. METHODS: In a multicentre prospective cohort study of 398 infants (age <1 year, male 59%) hospitalized for bronchiolitis, we applied clustering approaches to identify mycotypes by integrating nasopharyngeal fungus (detected in RNA-sequencing data) and virus data (respiratory syncytial virus [RSV], rhinovirus [RV]) at hospitalization. We examined their association with bronchiolitis severity-defined by positive pressure ventilation (PPV) use and biological characteristics by nasopharyngeal metatranscriptome and transcriptome data. RESULTS: In infants hospitalized for bronchiolitis, we identified four mycotypes: A) fungi(M.restricta)virus(RSV/RV), B) fungi(M.restricta)virus(RSV), C) fungi(M.globosa)virus(RSV/RV), D) fungi(not-detected)virus(RSV/RV) mycotypes. Compared to mycotype A infants (the largest subtype, n = 211), mycotype C infants (n = 85) had a significantly lower risk of PPV use (7% vs. 1%, adjOR, 0.21; 95% CI, 0.02-0.90; p = 0.033), while the risk of PPV use was not significantly different in mycotype B or D. In the metatranscriptome and transcriptome data, mycotype C had similar bacterial composition and microbial functions yet dysregulated pathways (e.g., Fc γ receptor-mediated phagocytosis pathway and chemokine signaling pathway; FDR <0.05). INTERPRETATION: In this multicentre cohort, fungus-virus clustering identified distinct mycotypes of infant bronchiolitis with differential severity risks and unique biological characteristics. FUNDING: This study was supported by the National Institutes of Health.