RSV disease severity is influenced by innate immune responses, viral loads and patient age.
Respiratory syncytial virus (RSV) is a leading cause of hospitalization in children, although most cases result in mild disease. A better understanding of the different clinical, immunologic and virologic factors present in infants with mild versus severe RSV disease will enable the development of effective antivirals and vaccines.
In a new study funded by the National Institute of Allergy and Infectious Diseases, researchers at Nationwide Children’s Hospital sought to identify the “safe and protective” immunoprofile induced by natural RSV infection that might protect infants from developing severe disease. Using a systems analysis approach, the researchers integrated blood transcriptional profiling and immune cell phenotyping with measurement of viral loads and clinical data from infants and young children with RSV infections of varying severity.
“We identified complex interactions among RSV viral loads, the innate immune response and patients’ age influencing disease severity,” says Asuncion Mejias, MD, PhD, senior author of the study, infectious disease specialist and principal investigator in the Center for Vaccines and Immunity at Nationwide Children’s and associate professor of Pediatrics at The Ohio State University College of Medicine.
Dr. Mejias and her colleagues demonstrated that children with mild disease, managed as outpatients, had higher RSV loads measured in the upper respiratory tract. Those with more severe disease were managed as inpatients and had increased numbers of poorly activated monocytes. Older children with mild disease showed greater expression of interferon genes compared with inpatients with severe disease, who showed greater activation of inflammation genes irrespective of age.
“Our data suggest that mild RSV infection is characterized by robust interferon expression, adequate monocyte activation and higher viral loads,” says co-senior author Octavio Ramilo, MD, chief of Infectious Diseases and principal investigator in the Center for Vaccines and Immunology at Nationwide Children’s.
Dr. Ramilo, also the Henry G. Cramblett Chair in Medicine and professor of Pediatrics at The Ohio State University College of Medicine, says their findings show the importance of both disease severity and age in children with RSV infection.
“A robust interferon response appears to play a protective role, while an uncontrolled inflammatory response is detrimental,” he says.
Drs. Mejias and Ramilo hope their findings can be used to help design and evaluate new vaccines and antivirals directed against RSV and inform research into other infectious diseases.