Yale researchers have found a way to spot new viruses

Testing negative swabs for an antiviral protein can help identify samples for further testing.
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The havoc and horror an emerging virus can wreak has been made very clear by SARS-CoV-2. And history makes clear that COVID-19 will not be the last pandemic.

Attempting to find new viruses with pandemic potential before they can jump into humans could be key to heading off the next one. Researchers search the globe looking for viruses in animals both wild and domestic, perform controversial gain-of-function experiments to try and identify dangerous mutations, and try to design vaccines with the ability to preemptively fight new diseases.

A Yale-led team has identified a single molecule that can reveal the presence of an unknown virus.

But a Yale-led team believes they have a much more pedestrian place to look for early warning signs: in the noses of people in hospital. And they have identified a single molecule that reveals the presence of an unknown virus.

“Finding a dangerous new virus is like searching for a needle in a haystack,” Ellen Foxman, lead author of the Lancet Microbe published study and associate professor of laboratory medicine and immunobiology at the Yale School of Medicine, said

“We found a way to significantly reduce the size of the haystack.”

Negative tests, positive insights: The study builds on previous work done by Foxman and Mary L. Landry published in the Journal of Infectious Diseases back in 2017. 

The research hinged on what most would consider useless medical waste: 251 nasal swabs taken from patients with a suspected respiratory disease but who had tested negative for any of the 10 most common viruses, including influenzas A and B, RSV, and rhinoviruses, the main cause of the common cold

Despite the fact that no virus was identified, the researchers noticed that some of the negative tests still showed signs of a virus being present — just not one of the usual suspects. The strongest signal was the production of the antiviral protein CXCL10 by cells lining the nasal passage, which are on the immune system’s front line.

Full genetic sequencing of the samples found with this antiviral protein uncovered hidden pathogens, including influenza type C — a rare and unexpected find. 

If nasal swabs that test negative for the usual suspects have the molecule, it can tell researchers to search for less common viruses — perhaps even new ones.

The nose knows: For their new study, swabs taken at the Yale New Haven Health Center in March 2020 were added to the analysis from 2017.

The goal was to find out if the presence of CXCL10 could be used as a biomarker for spotting which swabs may contain hidden, and perhaps unknown, respiratory viruses.

“We took all the samples that tested negative for viruses and we asked: ‘In these patients, did the body think that it was fighting a virus?’” Foxman told Connecticut Public. “And the way we could do that is by eavesdropping on the immune response in the nose.”

Almost 60% of the samples from March tested negative for all of the viruses on the standard screen; of those, only 9% of the negative samples ended up testing positive for CXCL10. But among them were four cases of the then-novel virus behind COVID-19, which had gone undiagnosed at the time.

“Finding a dangerous new virus is like searching for a needle in a haystack. We found a way to significantly reduce the size of the haystack.”

Ellen Foxman

The results point to CXCL10 screening as a potential way to spot emerging viruses early, by showing which negative swabs may be harboring unknown viral foes, giving doctors new insights into how to treat these patients — and perhaps giving researchers and public health officials advance warning to ward off the spread of infectious disease.

“It’s almost guaranteed that there’ll be another emerging virus,” Foxman told Connecituct Public. 

“Can we find that early enough to develop tests and vaccines very early on so that we can reduce the level of impact, and reduce the level of disruption like what we saw in the last few years?”

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