Immune profiles provide insights into respiratory syncytial virus disease severity in young children

Abstract

Respiratory syncytial virus (RSV) is associated with major morbidity in infants, although most cases result in mild disease. The pathogenesis of the disease is incompletely understood, especially the determining factors of disease severity. A better characterization of these factors may help with development of RSV vaccines and antivirals. Hence, identification of a “safe and protective” immunoprofile induced by natural RSV infection could be used as a as a surrogate of ideal vaccine-elicited responses in future clinical trials. In this study, we integrated blood transcriptional and cell immune profiling, RSV loads, and clinical data to identify factors associated with a mild disease phenotype in a cohort of 190 children <2 years of age. Children with mild disease (outpatients) showed higher RSV loads, greater induction of interferon (IFN) and plasma cell genes, and decreased expression of inflammation and neutrophil genes versus children with severe disease (inpatients). Additionally, only infants with severe disease had increased numbers of HLA-DRlow monocytes, not present in outpatients. Multivariable analyses confirmed that IFN overexpression was associated with decreased odds of hospitalization, whereas increased numbers of HLA-DRlow monocytes were associated with increased risk of hospitalization. These findings suggest that robust innate immune responses are associated with mild RSV infection in infants.

The Contribution of Neutrophils to the Pathogenesis of RSV Bronchiolitis

“…CD18 and ICAM-1 expression on neutrophils are also increased in RSV-infected infants compared with uninfected control infants [119]. In a more recent study, the addition of physiological concentrations of neutrophils to human RSV-infected nasal cultures in vitro increased epithelial cell damage, characterised by lower ciliary activity, cilium loss, less tight junction expression, and greater detachment of epithelial cells, compared to cultures with RSV-infected epithelial cells alone [120]. High-throughput analysis of lung-infiltrating neutrophils using the latest transcriptomic and high-dimensional flow cytometry is now needed to better identify different neutrophil subsets and associate these with beneficial and deleterious outcomes.…”

Behavioral strategies to prevent and mitigate COVID-19 infection

“…Their results suggest that the phenotypic and transcriptomic signature of mild RSV infection was characterized by an increase in IFN and plasma cell genes compared with patients with severe infection. 64 Moreover, the therapeutic efficacy of monoclonal antibodies with paratopes specific for G and F to minimize symptoms of disease in passively immunized children also provides support. 65 , 66 , 67 Antibodies specific for the influenza lipid membrane protein haemagglutinin (HA) are directly neutralizing, but antibodies with specificity to neuraminidase (NA) and matrix (M)2 protein also confer protection.…”

Pediatric Cancer Research: Surviving COVID-19

“…32,33 Interestingly, children with mild RSV disease (outpatient care) have recently been shown to have higher viral loads, greater induction of IFN genes and decreased gene expression of inflammation and neutrophils versus children with severe RSV (inpatient care). 34 Taken together, epidemiologic and immunologic data on SARS-CoV-2 infection are emerging that may be helpful to explore why pediatric patients experience less severe COVID-19 and to implement potential therapies that would either augment helpful or inhibit harmful immune responses to SARS-CoV-2. 35…”