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Researchers See Immune, Age Contributors to Childhood Respiratory Virus Response

NEW YORK – A research team from the US and Spain has identified distinct immune responses, viral load features, and other differences in infants and young children who experience more severe respiratory syncytial virus (RSV) infections.

Overall, the results "suggest that robust innate immune responses are associated with mild RSV infection in infants," co-corresponding authors Asuncion Mejias and Octavio Ramilo, with the Research Institute at Nationwide Children's Hospital Center for Vaccines and Immunity, and their colleagues reported.

Using a systems approach, the researchers integrated array-based transcriptional clues and flow cytometry-based immune cell population profiling on 190 infants or toddlers with or without RSV infections for a study published in Science Translational Medicine on Wednesday. Such infections are usually mild, but can lead to hospitalization or even death in a subset of affected children, they explained.

The team combined and compared clinical, RSV load, white blood cell immune features, and/or transcriptome data for up to 125 RSV-infected children and 65 unaffected children under the age of two years for the discovery and validation stages of the study.

With this approach, the investigators saw signs that enhanced interferon and plasma cell immune activity, and observed that higher-than-usual viral load appeared to coincide with milder RSV cases, meaning children could be treated for their infections in an outpatient setting.

"Counterintuitively, outpatients with mild RSV infection had higher RSV loads than those hospitalized with severe disease," the authors wrote. "There were also marked differences in immune gene patterns, as children with mild disease and older age showed greater expression of [interferon] compared with inpatients with severe disease."

On the other hand, children with severe RSV infections tended toward more pronounced expression of inflammatory and neutrophil immune genes, the researchers reported. Their results suggested that infants with severe disease had still other immune differences, including an increase in representation by monocyte immune cells with dialed down expression of a human leukocyte antigen called "antigen D."

Nearly 90 percent of the children participating in the study were 12 months old or younger, the authors noted, while milder, outpatient infections tended to be more common in the older children considered.

"By enrolling infants and young children spanning the disease severity spectrum and across different ages, we uncovered a complex interaction between RSV replication, the innate immune responses, and age," the authors wrote.

More broadly, the RSV-infected children had a greater proportion of neutrophil and monocyte cells in their white blood cell profiles compared to uninfected children, but lower representation by lymphocytes and other immune cells — a pattern that held in children with or without severe responses to their RSV infections.

These and other findings from the study "provide valuable insights into the host immune response to RSV and its relation to disease severity," the authors concluded, "and might be useful for designing clinical studies evaluating novel vaccines and antivirals directed against RSV."