By studying a cohort of 190 children, a research team has discovered important clues that could help explain why some children with respiratory syncytial virus (RSV) infections get mild cases while others get more severe disease and require hospitalization. The results identify important features in the immune response to RSV and could inform the development of a historically elusive vaccine for the disease. RSV is a common disease in children and represents the most frequent cause of hospitalization in newborns in developed countries, although it most often causes only mild symptoms. Studies have hinted that factors ranging from age to viral load can influence the severity of infections, but scientists had not fully understood how these factors affect the course of the disease on the biological level. Researchers also suspect that more severe cases are tied to abnormal responses from the immune system. To investigate, Santtu Heinonen and colleagues compared immune signatures in blood samples taken from a group of 190 young children, including 125 children with RSV infections and 65 healthy controls. Surprisingly, the authors saw that children who developed mild cases actually harbored higher viral loads compared with children who required hospitalization and had a higher likelihood of being infected with rhinovirus or another respiratory virus. The children with mild cases also displayed higher activity of genes involved in the production of interferons - molecules that are important in the innate immune response - but had less expression of inflammatory genes. The authors say their findings support a key role for innate immunity in determining the severity of RSV infections, and believe their results could help the design of clinical studies to evaluate new vaccines and antivirals against RSV.
Science Translational Medicine