Respiratory syncytial virus (RSV) remains the top cause of hospitalization among young children, leading to respiratory issues like bronchiolitis and pneumonia. However, the reasons why some children experience only mild symptoms while others suffer from severe disease are not well understood.

To better understand what happens in these cases, clinician-scientists from Brigham and Women's Hospital, a founding member of the Mass General Brigham health care system, and Boston Children's Hospital analyzed samples from patients' airways and blood, finding distinct changes in children with severe cases of RSV, including an increase in the number of natural killer (NK) cells in their airways.

The descriptive study, which focuses on understanding the underpinnings of severe disease, may help to lay groundwork for identifying new targets for future treatments. Results are published in Science Translational Medicine.

"As a physician, I help to care for children who have the most severe symptoms, and as a researcher, I'm driven to understand why they become so sick," said corresponding author Melody G. Duvall, MD, Ph.D., of the Division of Pulmonary and Critical Care Medicine at Brigham and Women's Hospital (BWH) and the Division of Critical Care Medicine at Boston Children's Hospital.

"NK cells are important first responders during viral infection—but they can also contribute to lung inflammation. Interestingly, our findings fit with data from some studies in COVID-19, which reported that patients with the most severe symptoms also had increased NK cells in their airways. Together with previous studies, our data link NK cells with serious viral illness, suggesting that these cellular pathways merit additional investigation."

Duvall and colleagues, including lead author Roisin B. Reilly of the Division of Pulmonary and Critical Care Medicine at BWH, looked at samples from 47 children critically ill with RSV, analyzing immune cells found in their airways and peripheral blood. Compared to uninfected children, those with severe illness had elevated levels of NK cells in their airways and decreased NK cells in their blood. In addition, they found that the cells themselves were altered, both in appearance and in their ability to perform their immunological function of killing diseased cells.

Duvall and co-authors have previously described a post-pandemic surge in pediatric RSV infections. While clinicians can only provide supportive care to the most severely sick children, vaccines to prevent RSV are now available for children 19 months and younger, adults 60 years and over, and people who are pregnant.