Respiratory Syncytial Virus (RSV) is a common childhood disease. Most people catch and recover from it by the age of three.

2022 was different, though. There was a severe and early outbreak of RSV that overwhelmed hospitals.

That year, Steven Szczepanek, associate professor in the Department of Pathobiology and Veterinary Science in the College of Agriculture, Health and Natural Resources (CAHNR), started a conversation with Dr. Ian Michelow, the head of pediatric infectious diseases and immunology at Connecticut Children’s and professor of pediatrics at UConn Health.

Szczepanek and Michelow suspected that there may have been mutations in the genome of the virus that were making it much more dangerous for more children that year.

Viruses like RSV are prone to mutations because, unlike human and animal cells, they don’t have the same “proofreading” enzymes that make sure a gene is copied without error during replication.

The group began collecting samples from child patients at the end of the 2022-23 respiratory disease season. In collaboration with Dr. Kevin Dieckhaus, professor of medicine and public health sciences and head of infectious diseases at UConn Health, they collected adult samples as well.

The researchers compared the samples collected from patients who had severe and mild cases of the disease. They identified 19 mutations that were consistent across the samples from children with more severe cases. These findings were published in bioRxiv.

“There were 19 mutations that were consistently different between the kids that had mild disease and those that had severe disease,” Szczepanek says. “It was the same mutations in the kids with severe disease that were different than those that had mild disease.”

The researchers cultured samples in the lab and found that the viruses with the mutations associated with greater disease severity also replicated much faster. The severe disease samples replicated 10 to 100 times more than the mild samples in the same amount of time. This was likely due to the mutation on a gene responsible for viral replication.

Faster replication is a generally accepted proxy for virulence, or how easily a virus spreads from one person to another.

“Generally speaking, the faster virus replicates, the more virulent it is, because it can create more copies of itself in a given period of time,” Szczepanek says. “And the more copies of a virus you have in your body, generally speaking, the worse off you are.”

These findings could have clinical significance by helping doctors better understand who is more at risk for severe disease.

“We don’t know why one child will have a mild cold, whereas another child may need to go to the ICU for care [with RSV],” Michelow says. “That’s always been a challenge in the field, and if you can predict which children are going to get sicker, that’s really important, because then you can offer greater supportive care up front.”

The researchers are also interested in continuing this work to determine if recent developments in RSV vaccines for pregnant mothers and newborns could be driving these mutations.

“Even though it’s protecting babies, could it have a side effect that’s putting pressure on the virus?” Michelow says. “Because now the virus has to protect itself against these antibodies, which will neutralize it, and change even more so.”

While RSV is most common in young children, it can also be dangerous for people over 65.

Determining what makes disease more severe in adults is trickier than in child populations because adults tend to have more health conditions that complicate infections. The researchers are collaborating with Hartford Hospital and St. Francis Health Center to review chart information for these patients in an ongoing study.

“The adults are different,” Dieckhaus says. “The comorbidities are pretty significant. But a lot of the concepts are going to be pretty similar.”

While this was a small study with only a handful of samples, the researchers have continued collecting samples in subsequence RSV seasons. This will allow them to look at how the virus is changing over time.

The researchers emphasize how this project was a collaboration between clinical and lab-based expertise that involved researchers, clinicians, medical students, graduate students, and undergraduates.

“There’s education percolating all throughout this project,” Dieckhaus says.

This work relates to CAHNR’s Strategic Vision area focused on Enhancing Health and Well-Being Locally, Nationally, and Globally.

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