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 RSV-infected 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.
Bibliographical noteThe authors thank the children and their parents for participating in this study, and the nurses and medical staff of the Department of Pediatrics at the Radboud University Medical Center and Canisius Wilhelmina Hospital for assistance in obtaining clinical samples. The authors are grateful to Elles Simonetti and Kim van der Weerd for their contribution in the laboratory. In addition, the authors thank Eva Voorbrood and Paul Ruijs from the Laboratory of Hematology at the Radboud University Medical Center for counting the blood smears.
The study was financially supported by the VIRGO consortium, an Innovative Cluster approved by the Netherlands Genomics Initiative and partially funded by the Dutch Government (BSIK 03012), The Netherlands.