Study Backs Use of Saliva COVID-19 Test

Sept. 4, 2020 -- A COVID-19 saliva test developed by researchers at Yale University appeared to perform at least as well as nasal swabs in a study of hospital patients, a finding that may help encourage more frequent use of self-collected samples.

In a letter published Aug. 28 in TheNew England Journal of Medicine, Anne L. Wyllie, PhD, of the Yale School of Public Health, and her co-authors reported on testing done on 70 patients. These patients already had tested positive for COVID-19, which was confirmed with a positive nasal swab.

One to 5 days after diagnosis, 81% of the saliva samples were positive, as compared with 71% of the nasal swab tests, Wyllie and co-authors say.

The New England Journal of Medicine (NEJM) publication expands on work previously reported by Wyllie and colleagues in an April preprint article posted to the site medRxiv.

These findings represent "an important advance in testing" for COVID-19, says Jason Farley, PhD, of Johns Hopkins Schools of Nursing and Medicine in Baltimore. An infectious disease-trained nurse epidemiologist, Farley was not involved in the Yale team work, but he has worked on efforts at Hopkins to test people using saliva samples to track COVID-19 infection.

The approach used by the Yale team avoids the kind of issues with shortages of medical supplies that have hampered U.S. testing, Farley says. Their approach relies on supplies hospital labs are likely to have on hand. The letter in NEJM, for example, said sterile urine cups were used to gather samples.

"This moves us forward, especially with supply chain issues," he says of the new research.

Wyllie and Nathan Grubaugh, PhD, of the Yale School of Public Health, last month secured an emergency use authorization from the FDA for a related test protocol, called SalivaDirect​. The FDA said this was the fifth test it had authorized that uses saliva as a sample for testing for COVID-19. ​

But Yale's approach with SalivaDirect is different from that used with many diagnostics.

"A common question that we receive is, 'What company is behind this assay?' The answer is -- well, there isn't one. We designed and validated SalivaDirect using several common and available reagents. If one reagent is out of stock or is too pricey, there are alternative reagents to use," says a paper on the CovidTrackerCT website, created by members of Grubaugh's lab.

SalivaDirect is a protocol, not a kit, which is intended to help other medical institutions also do "inexpensive saliva-based" testing, the paper says.

"I love the fact that they are sharing their protocols in an open-source way so that people can replicate the protocol," Farley says. The Yale team "really needs to be commended for that level of scientific integrity."

The University of Illinois already has used the FDA's emergency use authorization for Yale's protocol as a path for using its own saliva testing at the school. The researchers did what's called a bridging study that put their project under the umbrella of the FDA's emergency approval of the Yale test.

New Challenges

A challenge in COVID-19 testing is shifting institutions away from the kinds of tools they have been using and toward newer ones, says Martin Burke, MD, a professor of chemistry at the University of Illinois.

The NEJM publication on Yale's research may help widen the use of saliva-based tests, he says.

"I'm hopeful it is going to help overcome that inertia and help us get to a place where we could test much more [quickly] and frequently," says Burke, who is an associate dean of research for the Carle Illinois College of Medicine.

"Saliva is the medium that matters. This is how we transmit SARS-Cov2 to one another primarily," he says. “So why not test the thing that is most important for that transmission?"

His school is using its saliva test, called I-COVID, to screen faculty, staff, and students. The test can yield results in hours. The University of Illinois now is testing about 60,000 people twice a week, using this screening as part of its efforts to stay open amid the pandemic, Burke says.

Another advantage of the saliva tests is that they give more than a yes-or-no answer about the infection, he says.

Hopkins's Farley says the use of COVID-19 saliva tests for hospital patients outside of clinical tests will pose a few challenges for staff.

"There are some practical issues to think about as you think about the scale-up and how well the patients do and do not understand the actual instructions they are given," but the problems are manageable, he says.

Greater access to and ease of COVID-19 tests are critical to preventing spread of the virus, Wyllie says.

"People need to stop thinking about just diagnostic testing," she says. "We need to have screening testing going forward. These screening tests don't necessarily have to be of the same standards as diagnostic tests."