Disease severity in children with bronchiolitis is not associated with infection by multiple viruses. We conclude that other factors, such as age, contribute to disease severity to a larger extent.

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BackgroundRespiratory viral infections follow an unpredictable clinical course in young children ranging from a common cold to respiratory failure. The transition from mild to severe disease occurs rapidly and is difficult to predict. The pathophysiology underlying disease severity has remained elusive. There is an urgent need to better understand the immune response in this disease to come up with biomarkers that may aid clinical decision making.MethodsIn a prospective study, flow cytometric and genome-wide gene expression analyses were performed on blood samples of 26 children with a diagnosis of severe, moderate or mild Respiratory Syncytial Virus (RSV) infection. Differentially expressed genes were validated using Q-PCR in a second cohort of 80 children during three consecutive winter seasons. FACS analyses were also performed in the second cohort and on recovery samples of severe cases in the first cohort.ResultsSevere RSV infection was associated with a transient but marked decrease in CD4+ T, CD8+ T, and NK cells in peripheral blood. Gene expression analyses in both cohorts identified Olfactomedin4 (OLFM4) as a fully discriminative marker between children with mild and severe RSV infection, giving a PAM cross-validation error of 0%. Patients with an OLFM4 gene expression level above -7.5 were 6 times more likely to develop severe disease, after correction for age at hospitalization and gestational age.ConclusionBy combining genome-wide expression profiling of blood cell subsets with clinically well-annotated samples, OLFM4 was identified as a biomarker for severity of pediatric RSV infection.

Background: current tools to predict the severity of respiratory syncytial virus (RsV) infection might be improved by including immunological parameters. We hypothesized that a combination of inflammatory markers would differentiate between severe and mild disease in RsV-infected children. Methods: Blood and nasopharyngeal samples from 52 RsVinfected children were collected during acute infection and after recovery. Retrospectively, patients were categorized into three groups based on disease severity: mild (no supportive treatment), moderate (supplemental oxygen and/or nasogastric feeding), and severe (mechanical ventilation). clinical data, number of flow-defined leukocyte subsets, and cytokine concentrations were compared. results: children with severe RsV infection were characterized by young age; lymphocytopenia; increased interleukin (IL)-8, granulocyte colony-stimulating factor (G-csF), and IL-6 concentrations; and decreased chemokine (c-c motif ) ligand (ccL-5) concentrations in plasma. The combination of plasma levels of IL-8 and ccL-5, and cD4 + T-cell counts, with cutoff values of 67 pg/ml, 13 ng/ml, and 2.3 × 10 6 /ml, respectively, discriminated severe from mild RsV infection with 82% sensitivity and 96% specificity. conclusion: This study demonstrates that the combination of cD4 + T-cell counts and IL-8 and ccL-5 plasma concentrations correlates with disease severity in RsV-infected children. In addition to clinical features, these immunological markers may be used to assess severity of RsV infection and guide clinical management.