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Wednesday 18 January 2017
RSV disease severity in children

The article we suggest this week - Nasopharyngeal Microbiota, Host Transcriptome, and Disease Severity in Children with Respiratory Syncytial Virus Infection, published last November on Am J Respir Crit Care Med - aims at assessing whether specific nasopharyngeal microbiota (clusters) are associated with distinct host transcriptome profiles and disease severity in children less than 2 years of age with RSV infection.

Globally, respiratory syncytial virus (RSV) is the most frequent viral cause of acute lower respiratory infections in children younger than 5 years of age, and it is responsible for significant morbidity worldwide and mortality in infants in the developing world. Disease severity in these infants has been linked to a dysregulated host immune response. Besides the direct virus–host interaction, certain bacterial members of the respiratory tract microbiome might influence host responses to RSV, therewith modulating inflammation and possibly disease severity. Recent reports suggest that the composition of the nasopharyngeal microbiome affects the overall risk of developing respiratory tract infections and is associated with the severity of acute respiratory symptoms. So, the authors conducted a prospective observational study in order to characterize the nasopharyngeal microbiota, using 16S-rRNA–based sequencing and analyzed whole-blood RNA transcriptional profiles in outpatients with RSV and infants hospitalized with an RSV infection, as well as healthy control subjects. They defined the nasopharyngeal microbiota profiles in infants with RSV disease and their relationship with host immune responses and disease severity.
A total of 132 children, 106 with RSV infection and 26 healthy control subjects, were enrolled. Overall, children hospitalized with RSV infection were younger than outpatients with RSV and healthy control subjects. The inpatients were treated with antibiotics more frequently than outpatients (P < 0.0005).
The authors identified five 'major' Operational taxonomic Units (OTUs), including  Haemophilus influenzae, Streptococcus, Corynebacterium, Moraxella, or Staphylococcus aureus and five minor classifier taxa. The abundance of H. influenzae and Streptococcus OTUs was positively associated with RSV hospitalization (P = 0.005 and P = 0.004, respectively), whereas S. aureus abundance was inversely associated with the need for hospitalization (P = 0.025). In addition, high abundance of Moraxella was observed most often in outpatients (P = 0.034).
Data revealed an increased expression of IFN-related modules in patients with RSV, regardless of the microbiota profiles. However, expression of inflammation modules were higher in the H. influenzae–and Streptococcus-dominated clusters compared with the S. aureus cluster. In contrast, B cell, T cell, and cytotoxic/natural killer cell modules were overall underexpressed, which was particularly evident for the H. influenzae– and Streptococcus-enriched clusters. Last, there were differences in median expression values of inflammation and neutrophil module–associated genes between the different clusters. Data showed an additive effect of the presence of Streptococcus and H. influenzae on the RSV-induced host immune response, characterized by stronger activation of inflammatory pathways, which in turn might be related to a more severe RSV disease phenotype.
The authors observed that infants within H. influenzae– and Streptococcus enriched clusters mounted a distinct host inflammatory response characterized by overexpression of genes related to TLR signaling and neutrophil recruitment and activation, as compared with children with another microbiota composition, particularly those in the S. aureus cluster. This study was the first to assess the interrelation between the upper respiratory tract microbiome and the host systemic transcriptome immune response in young children with RSV infection and to document how these interactions might influence the clinical disease phenotype.
The authors concluded that a nasopharyngeal microbiota composition, characterized by H. influenzae and Streptococcus as opposed to S. aureus, is associated with a distinct host inflammatory immune response and enhanced disease severity as defined by more frequent need for RSV hospitalization.

AUTHORS: W.A. de Steenhuijsen Piters, S. Heinonen, R. Hasrat, E. Bunsow, B. Smith, M.C. Suarez-Arrabal, D. Chaussabel, D.M. Cohen, E.A. Sanders, O. Ramilo, D. Bogaert, A. Mejias