Learning from RSV Infections: Insight into Immune Response

RSV causes thousands of deaths in children - why do some have more severe disease?

While the world focuses on coronavirus disease 2019 (COVID-19), it’s important we continue efforts to prevent and control the spread of other infectious diseases. These efforts will become even more important as we move into the winter and several respiratory viruses begin to spread in greater frequency. Respiratory Syncytial Virus (RSV) is among those that frequently spread during this time. The Centers for Disease Control and Prevention (CDC) estimates that each year, there are 2.1 million outpatient visits related to RSV in children less than 5 years of age. Annually, the United States sees over 57,000 hospitalizations in children less than 5 and 14,000 deaths in those older than 65 years.

RSV infections tend to occur primarily in the fall, winter, and spring, with peak season often between late December to mid-February. RSV is a respiratory infection that tends to have symptoms such as a fever, runny nose, cough, short periods of apnea, wheezing, etc. For those children with pre-existing conditions or a weakened immune system, RSV can be deadly. An RSV outbreak going through a neonatal intensive care unit (NICU) can be devastating and something infection prevention and healthcare personnel work feverishly to prevent.

A difficulty with RSV infections is that some children have more mild illness while others are critically ill. A new study is shedding light on these variances. Through the American Association for the Advancement of Science, a research team studied a cohort of 190 children less than 2 years in age, to help understand the variability in severity of RSV infections. Published in Science Translational Medicine, the research team “integrated blood transcriptional and cell immune profiling, RSV loads, and clinical data to identify factors associated with a mild disease phenotype in a cohort of 190 children <2 years of age. Children with mild disease (outpatients) showed higher RSV loads, greater induction of interferon (IFN) and plasma cell genes, and decreased expression of inflammation and neutrophil genes versus children with severe disease (inpatients).”

The team also found a higher level of HLA-DRlow monocytes in infants with severe RSV infections, which was unique to that subgroup. Induction of interferon overexpression was found to be statistically significant in relation to lower rates of hospitalization, the opposite outcome relative to those with higher numbers of HLA-DRlow monocytes.

The 190 children included 125 with RSV. Those requiring hospitalization due to severe illness were also more likely to have a co-infection with another respiratory virus like rhinovirus. As the authors noted, a more robust innate immune response appears to be associated with a more mild RSV infection in infants. Theses findings are especially helpful in understanding more severe disease predispositions and what might indicate if a patient is likely to require hospitalization or have severe infection. As RSV is a frequent infection in children and infants, there is a continued need for more studies to understand RSV and the pathophysiology that results in more severe illness and even morbidity.