Two new studies made the case recently for an alternative to the invasive Covid-19 tests that require collecting a sample from deep in the nose. Saliva samples, both studies found, were nearly as reliable and far less of a hassle.

Anne Wyllie, a researcher at the Yale School of Public Health who was the lead author of one of the studies, said she hopes the work helps quell some of saliva’s detractors.

“There’s been a lot of debate about saliva versus swab,” she said. “I think some of it is not entirely justified.”

The U.S. is more than six months into a global pandemic made worse by delayed and disorganized testing efforts and there’s still no clear consensus on who to screen, when to do it, or even what the best way to do so is. These studies suggest saliva could present a compelling alternative to other tests — one that does not necessarily require trained personnel to collect a sample and therefore use up valuable personal protective gear or put staff at risk. Even if the tests are marginally less accurate, the trade-off may be worth it.

A range of new testing options have been flooding the market since an initial shortage of the first provided by the Centers for Disease Control and Prevention. The Food and Drug Administration has issued emergency authorizations for more than 150 diagnostic Covid-19 tests, including those that rely on saliva and others that require a swab of deep in the nasal cavity, the front of the nose or the throat.

“The U.S. has undertaken this very differently from most other countries,” said Alan Wells, medical director of UPMC Clinical Laboratories at the University of Pittsburgh. “We’ve gone andproliferated dozens of different assays, which in this case is basically more confusing than helpful.”

What would be helpful, said Wells, is more guidance on when to use which test. 

“There should be a cheat sheet out there for what test to use when,” Wells said.

In Yale’s new saliva study, published last week in the New England Journal of Medicine, Wyllie’s team identified 70 hospital patients whose infections had already been confirmed with the more traditional nasal swabs. Studies have suggested that SARS-CoV-2, the virus that causes Covid-19, first binds to cells in the body’s nasal cavity and then begins replicating, spreading through the body’s respiratory tract. There’s little doubt that in this process, the virus also spreads to the body’s oral cavity. The question is whether there is enough virus to be spotted easily with a saliva test.

In the Yale study, the saliva tests actually detected the virus more frequently — 81% of the tests came back positive in the first five days of infections, compared to 71% of nasopharyngeal tests. The saliva test also detected more copies of the virus’s genetic material.

In a second study from Canada in Annals of Internal Medicine, that was also out last week, researchers tested nearly 2,000 people with either mild symptoms of the virus or no symptoms but at a high risk of infection. Participants collected their own saliva and also took the traditional swab test: 34 came back positive in both tests. In 14 cases, virus was detected in the saliva sample, but not the nasal sample. In 22, the opposite was true.

Though the nasal sample had a slight edge in detecting infections, the University of Ottawa researchers said the study made a case for saliva samples. 

“Saliva testing presents potential advantages,” the researchers wrote. “Collection does not require trained staff or personal protective equipment, can be done outside testing centers, and may be better tolerated in challenging or pediatric populations.”

On top of debates over which way to test is best, there’s been added confusion over who should be tested, particularly as schools and colleges reopen, since the CDC issued guidance suggesting that those without symptoms “do not necessarily need a test.”

Wyllie said many saliva-test detractors may simply be uncomfortable working with it.

“What we desperately need right now is just more testing,” she said. “And maybe just having those different options available means that we can get more testing out there.”

Wells said though that there are still significant questions about whether saliva tests are as good.

In approving Yale’s SalivaDirect test, which was developed based on Wyllie’s study, the FDA noted potential upsides as well as differences among the saliva tests it vetted.

But different tests might be better in different scenarios, depending on whether a test aims to screen individuals, diagnose the virus,  or conduct surveillance, according to Davey Smith, head of the Division of Infectious Diseases and Global Public Health at the University of California San Diego.

“There is lots of misunderstanding about when to use what test,” he said. 

Some tests may be very sensitive but less specific — in other words, good at picking up the presence of virus when it is there but less good at saying when the virus is not there. Such tests might be useful, say, to screen school children or cruise ship passengers. Tests that are highly specific, on the other hand, are useful in places like nursing homes and emergency rooms. 

Speed and lower costs come with trade-offs, too, said Andrew Brooks, a professor at Rutgers University and chief executive of Infinity BiologiX, a company spun off last month from the school where it developed the first saliva test to receive emergency use authorization from the FDA.

“People want a test to be cheap, fast and the most sensitive and specific,” he said. “But you can’t have all three of those things with the technology we have today.” 

Antigen tests, for example, he said, may present more accuracy issues but they’re also far faster and so better in situations where speed is important. An antigen is a viral protein, or a piece of one, that indicates the pathogen’s presence.

“What is the absolute right test? It depends on the situation,” Brooks said.