Study predicts which kids hospitalized with RSV likely to worsen

April 5, 2021

Children hospitalized with breathing problems due to infection with respiratory syncytial virus (RSV) are likely to get sicker and remain hospitalized if they have high levels of defective copies of the virus, according to a new study by researchers at Washington University School of Medicine in St. Louis.

The findings, published in Nature Microbiology, could help doctors identify those patients at high risk of severe illness due to respiratory syncytial virus (RSV), the most common cause of pneumonia and bronchiolitis (inflammation of the small airways) in children under age 5.

“Every child has been infected by RSV at least once before the age of 3,” said senior author Carolina B. López, PhD, Professor of Molecular Microbiology and a BJC Investigator. “Some infants and small children will just develop a cold, but others end up hospitalized. We don’t really know what determines whether a child will get really sick or not. So when babies are admitted to the hospital with RSV, doctors don’t have a way to predict whether they will be discharged in a day or two, or end up in intensive care.”

The new findings could lead to a way for doctors to triage people who arrive in the emergency room wheezing from an RSV infection and direct the most intensive interventions to those most at risk of getting even sicker, López added.

The researchers previously discovered that RSV, as it multiplies, makes some nonfunctional copies of its genome. These defective viral genomes are missing crucial sections, so they can’t form new infectious viruses, but they do trigger a strong antiviral immune response.

To find out whether the presence of defective viral genomes affects how sick people get, the researchers analyzed viral RNA in nasal washes from 122 children under age 2 who had been hospitalized with RSV. Defective viral genomes were found in 100 (82%) of the children. Those with defective viral genomes got sicker and stayed in the hospital longer than those without.

The used polymerase chain reaction, or PCR, to identify the defective viral genomes in infected people.

Further studies with infants who had been naturally infected with RSV but not hospitalized, and with healthy young adults who had been experimentally infected, showed that the health consequences of the defective genomes depend on when they show up in the course of illness. Those children and adults who generate detectable levels of defective genomes early in the course of an infection had shorter and milder illnesses than those whose defective viral genomes were not detected until later or those who never developed defective genomes at all.

“The defective genomes are kind of a proxy for the immune response,” López said. “No matter when in the course of infection we detect defective genomes, we see a stronger immune response. But timing matters here. A strong immune response very early after infection is good because it prevents the virus from multiplying. But if the immune response comes too late, when the virus has already multiplied, it is likely very damaging and leads to more severe illness.”

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