Nose swab may help predict which children will have worse outcomes from RSV

A test using a nasal swab biopsy could help predict which children presenting with RSV are likely to develop severe disease. The test would use a specific genetic marker of nasal mucosal membrane injury caused by the virus. The gene expression pattern was identified in a recent study by researchers at Northwestern University, published in Frontiers in Immunology. “The ability to identify which infants with RSV in intensive care will recover quickly and which patients will require a longer stay would provide invaluable information to parents and medical providers,” said Dr. Bria Coates, lead author. She is an assistant professor of pediatrics at the Northwestern University Feinberg School of Medicine. The study investigated immunologic responses in the nasal mucosa of infants with critical bronchiolitis and identified which gene signatures were associated with clinical outcomes and length of stay. Injury in the nasal mucosal membranes of children with RSV may be a marker of a dysregulated response to the virus and predict length of illness, researchers posited. Most RSV infections are mild, with symptoms staying confined to the upper respiratory tract. However, up to 2% of children under one year of age require hospitalization, and the disease is responsible for about 25% of acute lower respiratory tract infections in children less than five years old, the study said. At this point, there is no tool that can help predict which infants with RSV bronchiolitis and admitted to the pediatric intensive care unit (PICU) will recover quickly and which ones will need prolonged respiratory support. In general, the nasal mucosa has three cell types: ciliated cells (which help clear mucus); secretory cells; and basal cells (a type of stem cell which can differentiate into other cells to replace damaged ones and help regenerate damaged epithelium). Ciliated cells are the main type of cell infected by RSV. For the study, participants were recruited from December 2017 through April 2018, and December 2019 through April 2020. All were all admitted to the PICU at Chicago Children’s Hospital, were under two years of age, tested positive for RSV infection and had symptoms of pulmonary parenchymal disease. The analysis used a cohort of 33 participants. Nasal mucosa samples were obtained by mucosal scrape biopsy and RNA sequencing and analysis conducted. As for the clinical course of the infants, 10 needed invasive mechanical ventilation (IMV), and 23 received non-invasive respiratory support (NIS). Nasal samples were collected within three days of admission for 28 of the 33 participants (85%). The infants who received IMV were similar in age, gestational age at birth, race and ethnicity to those that received NIS. Participants who received IMV had a longer length of stay and longer respiratory support than the participants receiving NIS. The researchers then compared gene expression findings between the infants who required NIS for a shortened duration (up to three days), to those who had a prolonged stay (more than three days)—although both groups were clinically indistinguishable when the sampling was conducted. “We identified an association between nasal gene expression and clinical outcomes in infants with critical RSV bronchiolitis,” the study said. Infants whose samples showed increased expression of basal cell genes had shorter stays, while those who require stay of more than three days had increased expression of ciliated cell genes. According to Dr. Coates this makes sense because RSV primarily infects ciliated cells. The infection causes destruction of cilia—the fine hairs that help clear out mucus. As well, infected ciliated cells become dysmorphic and slough into the airways adding to respiratory symptoms. “In essence, increased injury in the nasal mucosal membranes of children with RSV may be a marker of a dysregulated response to the virus and can help predict which individual patients will have more prolonged illness,” she said. A nasal swab test that looks for genetic markers for ciliated cell activity is something that most hospitals could do one day. It would need to be a PCR test for the RNA, and PCR tests usually take a few hours, she said. “The ability to predict the duration of illness in infants with critical RSV bronchiolitis using a non-invasive nasal sample would provide invaluable prognostic information for parents and medical providers. In addition, identifying gene signatures associated with specific patient endotypes may inform the allocation of resources and development of therapeutics,” the study concluded. According to Dr. Alan Kaplan, a clinical lecturer at the University of Toronto the risk of viral progression is currently based on immunity and comorbidities. “For RSV infection we consider prematurity and lung development as risks. This study looks at factors that we do not usually consider as they are not things we can currently measure. By looking at genes related to ciliary function, the authors could predict those infants who will require a longer duration of bronchiolitis.” He was not involved in the study. The idea of testing for gene expression “could have benefits for predicting more prolonged hospitalizations with the use of non-invasive nasal samples. Perhaps in the future it could also predict those with high risk of more severe disease for other interventions such as vaccination or monoclonal antibody treatments.”

Nose swab may help predict which children will have worse outcomes from RSV

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