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A COVID-19 saliva test protocol 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 August 28 in the New England Journal of Medicine, Anne L. Wyllie, PhD, of the Yale School of Public Health, New Haven, Connecticut, and her coauthors reported on testing done on 70 patients. These patients already had tested positive for COVID-19, which was confirmed with a positive nasopharyngeal swab specimen at admission to Yale-New Haven Hospital.
At 1 to 5 days after diagnosis, 81% (95% CI, 71-96) of the saliva samples were positive, as compared with 71% (95% CI, 67-94) of the nasopharyngeal swab specimens, Wyllie and coauthors report in the NEJM paper.
Wyllie told Medscape Medical News that, at days 6 to 10 after diagnosis, 76% of the saliva samples were positive, as compared with 65% of the nasopharyngeal swab specimens. The results flip at the day 11 mark, with 41% of the saliva samples showing positive results, as compared with 50% of the nasopharyngeal swab specimens.
In the letter, Wyllie and coauthors also reported on screening results for 495 healthcare workers (ages 22-74 years; mean age, 37) who were asymptomatic for COVID-19. The researchers detected SARS-CoV-2 in saliva specimens obtained from 13 people who did not report any symptoms at or before the time of sample collection. Of these 13, nine had collected matched nasopharyngeal swab specimens by themselves on the same day and seven of these specimens tested negative. The 13 positive diagnoses were later confirmed with additional nasopharyngeal samples.
The 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, Jason Farley, PhD, MPH, of Johns Hopkins Schools of Nursing and Medicine, Baltimore, Maryland, told Medscape Medical News. 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 individuals using saliva samples to track COVID-19 infection.
The pragmatic approach used by the Yale team avoids the kind of issues with shortages of medical supplies that have hampered US testing, Farley said. Their approach relies on supplies hospital laboratories 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 said 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 US Food and Drug Administration (FDA) for a related test protocol, called SalivaDirect. This is a simplified version of the test described in the NEJM letter, with the researchers having eliminated the RNA extraction step. 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 markedly different from that used with many diagnostics, as the webpage for the test notes.
"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 backgrounder 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 backgrounder said.
"I love the fact that they are sharing their protocols in an open-source way so that people can replicate the protocol," Farley said. The Yale team "really needs to be commended for that level of scientific integrity."
Also enthusiastic about this protocol is Andy Slavitt, who was administrator of the Centers for Medicare & Medicaid Services in the Obama administration. In a series of tweets on August 15, Slavitt said the Yale team is "turning testing from a bespoke suit to a low-cost commodity."
SalivaDirect "should create millions more in test capacity. Easy to use. High volume. Cheap. Widely available and accurate," he tweeted.
The University of Illinois, Urbana-Champaign, 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 performed what's called a "bridging study" that put their project under the umbrella of the FDA's emergency approval of the Yale test.
A challenge in COVID-19 testing is shifting institutions away from the kinds of tools they have been currently using and toward newer ones, said Martin Burke, MD, PhD a professor of chemistry at the University of Illinois, Urbana-Champaign.
The NEJM publication on Yale's research may assist with wider adoption of saliva-based tests, he told Medscape Medical News.
"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," said Burke, who is associate dean of research for the Carle Illinois College of Medicine, Champaign, Illinois.
"Saliva is the medium that matters. This is how we transmit SARS-Cov2 to one another primarily," he said. “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 try to stay open amid the pandemic, Burke said.
Another advantage of the saliva tests is that they provide more than a binary yes-or-no answer about the infection, he said.
"You actually end up getting a quantitative readout on how many copies of viral RNA per milliliter in saliva," Burke said. "There's an extra dimension there of quantitative information that thus far we haven't really been taking advantage that could be a huge opportunity."
Hopkins' Farley said implementing 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," Farley said, adding, however, that the problems are manageable.
Yale's Wyllie said the research in the NEJM paper shows saliva to be at least as good as nasal swabs, and possibly better. And for SalivaDirect with a sensitivity of 6-12 virus RNA copies/µL it is still comparable to many other available PCR tests, she said.
Greater availability and ease of COVID-19 tests is critical to preventing spread of the virus, she added.
"People need to stop thinking about just diagnostic testing," Wyllie said. "We need to have screening testing going forward. These screening tests don't necessarily have to be of the same standards as diagnostic tests."
This work was supported by the Huffman Family Donor Advised Fund, a Fast Grant from Emergent Ventures at the Mercatus Center at George Mason University, the Yale Institute for Global Health, the Yale School of Medicine, a grant (U19 AI08992, to Dr. Ko) from the National Institute of Allergy and Infectious Diseases, the Beatrice Kleinberg Neuwirth Fund, and a grant (Rubicon 019.181EN.004, to Dr. Vogel) from the Dutch Research Council (NWO). In disclosures forms, the authors reported grants and personal fees outside of this work from Pfizer, Bristol-Myers Squibb, Regeneron, Serimmune, and the National Basketball Association.
N Eng J Med. Published online August 28, 2020. Letter
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Cite this: Saliva COVID-19 Test as Good as, Perhaps Beats, Nasal Swab: Study - Medscape - Sep 03, 2020.