Nasal swabs – Nasopharyngeal screening with CXCL10 could be used as a strategy to enrich samples containing undiagnosed viruses.
The COVID-19 pandemic has renewed the imperative to expand surveillance for unrecognized or emerging pathogens. For respiratory viruses, proposed approaches include isolation from animal sources, identification in pooled human respiratory samples, and outbreak surveillance, such as that which led to the initial identification of SARS-CoV-2. These methods can be added to metagenomic sequencing for viral identification and molecular epidemiology. Surveillance for unexplained outbreaks focuses on human pathogens but may detect emerging viruses too late, that is when the epidemic has already started.
However, Yale researchers have discovered that testing for the presence of a single immune system molecule in nasal swabs can help detect stealthy viruses not identified by standard tests.
The 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 are negative. But as they observed, in a few cases, swabs that did not have the “usual suspect” viruses still showed signs that antiviral defenses were activated, indicating the presence of a pathogen. The telltale sign was a high level of a single antiviral protein produced by the cells lining the nasal passages.
Building on that finding, the researchers applied extensive genetic sequencing methods to old samples containing the protein, and in one of them, they found an unexpected flu virus, called influenza C.
They 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 appeared in New York state around those same dates, testing was not available. Available until weeks later. Hundreds of nasal swab samples collected from patients at Yale-New Haven Hospital had tested negative for standard characteristic viruses. When tested for the immune system biomarker, the vast majority of these samples did not show any 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 results reveal that tests for an antiviral protein produced by the body, even if known tests are negative, can help pinpoint which nasal swabs are most likely to contain unexpected viruses.
Specifically, biomarker screening makes it possible to narrow down the search for unexpected pathogens, making vigilance possible using swabs collected during routine patient care. Samples can be tested with more complex genetic methods to identify unexpected or emerging pathogens circulating in the patient population and trigger a response from the healthcare community.