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Yale Team Finds Saliva Compares Favorably to Nasopharyngeal Swabs for SARS-CoV-2 Testing

NEW YORK – Yale researchers have found that saliva specimens provide similar, if not better, sensitivity than nasopharyngeal swabs for RT-qPCR-based SARS-CoV-2 testing and can detect the virus in asymptomatic individuals.

For a study published in the New England Journal of Medicine on Friday — which backed up conclusions from a MedRxiv preprint published in April — the researchers analyzed data from 70 inpatients with COVID-19. After the diagnosis was confirmed with a positive nasopharyngeal swab specimen at hospital admission, the investigators tested saliva specimens collected by the patients themselves during their hospitalization and nasopharyngeal swabs collected from them at the same time by healthcare workers.

Using primer sequences from the Centers for Disease Control and Prevention, the Yale School of Public Health's Anne Wyllie and her colleagues were able to detect more copies of viral RNA in the saliva specimens than in the nasopharyngeal swabs. Further, a higher percentage of saliva samples were positive up to 10 days after diagnosis. For example, at one to five days after diagnosis, 81 percent of the saliva samples were positive, as compared with 71 percent of the nasopharyngeal swabs.

"These findings suggest that saliva specimens and nasopharyngeal swab specimens have at least similar sensitivity in the detection of SARS-CoV-2 during the course of hospitalization," the authors wrote.

The researchers also evaluated viral detection in matched samples over time and found that the level of SARS-CoV-2 RNA decreased after symptom onset in both saliva and nasopharyngeal swab specimens. In three instances, a negative nasopharyngeal swab was followed by a positive swab at the next collection of a specimen, which happened only once with the saliva specimens. During the clinical course, they also saw less variation in levels of SARS-CoV-2 RNA in the saliva specimens than in the nasopharyngeal swabs.

To see whether they could detect the virus in asymptomatic people or outpatients, the researchers went on to screen 495 asymptomatic healthcare workers and used RT-qPCR to test both saliva and nasopharyngeal samples. They detected SARS-CoV-2 RNA in saliva specimens from 13 people who didn't report any symptoms at or before the time of sample collection. Of these, nine had collected matched nasopharyngeal swab specimens by themselves on the same day, and seven of these tested negative.

The diagnosis in the 13 healthcare workers with positive saliva specimens was later confirmed in diagnostic testing of additional nasopharyngeal samples, the researchers added.

They further noted that variation in nasopharyngeal sampling may be an explanation for the false negative results, and that nasopharyngeal swab specimens — collected by healthcare workers or self-collected — showed greater variation in the levels of human RNase P gene than the saliva specimens.

"Collection of saliva samples by patients themselves negates the need for direct interaction between healthcare workers and patients. This interaction is a source of major testing bottlenecks and presents a risk of nosocomial infection," the authors concluded. "Collection of saliva samples by patients themselves also alleviates demands for supplies of swabs and personal protective equipment. Given the growing need for testing, our findings provide support for the potential of saliva specimens in the diagnosis of SARS-CoV-2 infection."

Earlier this month, the US Food and Drug Administration issued Emergency Use Authorization to the Yale School of Public Health for its SalivaDirect COVID-19 diagnostic test, which uses a different method of collecting and processing saliva samples than previous saliva-based SARS-CoV-2 tests.

With SalivaDirect, a saliva sample can be collected in a sterile container, and the method does not require special types of swabs or collection devices. It also does not require a separate nucleic acid extraction step. SalivaDirect enables testing of low volumes of saliva using a dualplex RT-qPCR method for SARS-CoV-2 RNA detection. Saliva is first treated with proteinase K, followed by a heat inactivation step. The test uses validated primer and probe sets developed by the CDC.