Nasal Microbiota Changes are Associated with Progression to Lower Respiratory Infection Following Respiratory Syncytial Virus Upper Respiratory Infection in Hematopoietic Cell Transplant Recipients

Background. Respiratory syncytial virus (RSV) is one of the most common viral pathogens in hematopoietic cell transplant (HCT) recipients. It mainly causes upper respiratory infections (URIs), but it can progress in 1/3 of patients to lower respiratory tract infections (LRIs) with high subsequent mortality. Bacterial coinfections have been associated with viral LRI; however the serial changes in nasal microbiota and correlation with development of RSV-LRI in HCT recipients have not been investigated. We aimed to understand the serial changes, including decrease in bacterial diversity and domination by particular bacterial groups, in nasal microbiome and its association with development of RSV-LRI in HCT recipients. Methods. For a clinical trial in adult HCT recipients with RSV-URI, using a standardized collection method, we obtained weekly nasal wash samples from each patient up to day 30 from RSV diagnosis. These samples were analyzed by 16S ribosomal RNA gene sequencing and differences within and between patients were compared by assessing α-diversity (Shannon's index) and β-diversity (UniFrac method). Generalized linear regression modeling was utilized to compare the serial changes in bacterial relative abundance between those who progressed to RSV-LRI versus those who did not. Results. Of the 43 patients, the majority were white (25[58%]), female (22 [52%]), and underwent allogeneic HCT (30[70%]) for acute leukemia (17 [40%]). From analysis of 189 nasal wash samples (rarefaction: 1007 reads per sample), a significant loss of microbial diversity as early as 1 week was observed in patients who progressed to LRI versus those who did not. Principal component analysis (figure) also revealed 2 distinct clusters between patients who progressed to LRI (Proteobacteria: e.g. Parasutterella) versus those who recovered (Firmicutes: e.g. Staphylococcus) (figure, P = 0.001). Conclusion. A loss of diversity accompanied by increase of noncommensal bacterial groups was observed in patients with RSV who progressed to LRI. Perturbations in the nasal microbiome following viral infections during post-transplant period may be the harbinger of loss of the lung homeostatic immune defenses, leading to pneumonia, Learning more about the dynamic changes of nasal microbiome following RSV URI can add to risk stratification for patients who will progress to pneumonia. Figure: Beta Diversity Ordination Disclosures. D. P. Kontoyiannis, •: Advisory Board, Research support; Pfizer: Research grant, Research support; Gilead: Invited lecturer, Speaker honorarium; Astellas: Consultant, Research support and Speaker honorarium; F2G: Consultant, Consulting fee; T2 Biosystems: Invited lecturer, Speaker honorarium; Mylan Inc: Invited lecturer, Speaker honorarium