A Blood-Based Interferon Viral Score Defines Acute RSV Bronchiolitis in Infants

Background: Respiratory syncytial virus (RSV) is the leading cause of bronchiolitis and hospitalization in infancy. Reliable biomarkers reflecting host antiviral responses and disease dynamics are still lacking. Methods: We evaluated the expression of the interferon-stimulated genes IFI44L, IFI27, and RSAD2 in peripheral blood of infants hospitalized with RSV bronchiolitis at admission and discharge, and in healthy controls, using multiplex RT-qPCR. A composite interferon-based Viral Score was derived from coordinated ISG expression. Results: All three ISGs and the Viral Score were markedly elevated during acute RSV infection at hospital admission compared with discharge and healthy controls. Following clinical recovery, ISG expression and Viral Score declined significantly and approached baseline levels. The Viral Score clearly discriminated acute infection from recovery and healthy states, reflecting dynamic systemic interferon activation. Conclusions: A Viral Score based on IFI44L, IFI27, and RSAD2 captures systemic antiviral immune responses in infants with RSV bronchiolitis and declines with disease resolution. This interferon-based host-response signature represents a promising biomarker for defining viral infection status and monitoring disease dynamics in pediatric respiratory infections.