As the COVID-19 pandemic has shown, potentially dangerous new viruses can begin to spread in the population long before the global public health surveillance system can detect them.
However, Yale researchers have found that testing for the presence of a single immune system molecule in nasal swabs can help detect stealthy viruses not identified in standard tests, they report Jan. 1 in the journal Lancet Microbe.
“Finding a dangerous new virus is like looking for a needle in a haystack,” said Ellen Foxman, associate professor of laboratory medicine and immunobiology and lead author of the study. “We found a way to significantly reduce the size of the haystack.”
Public health officials often look to a few sources for warning signs of emerging diseases. They study emerging viruses in animals that can transmit the infection to humans. But determining which of the hundreds or thousands of new viral variants poses a real danger is difficult. And they look for outbreaks of unexplained respiratory illness, which is how SARS-Cov-2, the virus that causes COVID-19, was discovered in China in late 2019.
However, when an outbreak of a new virus occurs, it may be too late to contain its spread.
For the new study, Foxman and his team reviewed an observation made in their lab in 2017, which they thought might provide a new way to monitor for unexpected pathogens. Nasal swabs are commonly taken from patients with suspected respiratory infections and tested for specific signatures of 10 to 15 known viruses. Most of the tests come back negative. But as Foxman’s team observed in 2017, in some cases, swabs from those who tested negative for the “usual suspect” viruses still showed signs that antiviral defenses were activated, indicating the presence of a virus. The telltale sign was a high level of a single antiviral protein produced by cells lining the nasal passages.
Based on that finding, the researchers applied comprehensive genetic sequencing methods to old samples containing the protein and, in one sample, found an unexpected influenza virus, called influenza C.
The researchers also used this same strategy of retesting old samples to look for missing cases of COVID-19 during the first two weeks of March 2020. Although cases of the virus had emerged in New York state around the same time, evidence was not available. until weeks later. Hundreds of nasal swab samples collected from patients at Yale-New Haven Hospital during that time tested negative for standard characteristic viruses. When tested for the immune system biomarker, the vast majority of those samples showed no trace of antiviral defense system activity. But a few did; among them, the team found four cases of COVID-19 that had not been diagnosed at the time.
The findings reveal that testing for an antiviral protein produced by the body, even if tests for known respiratory viruses are negative, can help identify which nasal swabs are most likely to contain unexpected viruses.
Specifically, biomarker detection may allow researchers to narrow down the search for unexpected pathogens, making surveillance for unexpected viruses feasible using swabs collected during routine patient care. Samples containing the biomarker can be tested using more sophisticated genetic testing methods to identify unexpected or emerging pathogens circulating in the patient population and prompt a response from the healthcare community.
Yale’s Nagarjuna R. Cheemarla and Jason Bishai are co-senior authors of the paper, as are former Yale scholars Amelia Hanron and Joseph R. Fauver.