Saliva-Based COVID-19 Testing Set to Expand

[Originally published: Aug. 20, 2020. Updated: Jan. 25, 2022.]

Early in the pandemic, a saliva-based COVID-19 test developed by Yale researchers (called SalivaDirect) attracted attention as an easy method that could deliver accurate results quickly. 

In August 2020, the Food and Drug Administration (FDA) granted emergency use authorization (EUA) to SalivaDirect. The method has since been adopted throughout the country, and is now offered in more than 160 certified labs that must meet strict quality standards set by federal agencies. For the most part, however, a saliva-based test was not something the general public could obtain as easily as a test relying on a nasal sample. 

But that may now be changing. Recently, Yale Pathology Labs and the Yale School of Public Health partnered to offer SalivaDirect at two state-run COVID-19 testing sites in New Haven, Conn. What’s more—no appointments are necessary. And the vast majority of SalivaDirect results are delivered within 24 hours, says Anne Wyllie, PhD, a Yale School of Public Health research scientist and creator of SalivaDirect. 

The collection process is simple. A patient simply drools—but does not spit—into a sterilized container. The sample is then transferred to the Yale Pathology Labs. To detect the virus, lab technicians use PCR technology also used by COVID-19 tests that rely on a nasal swab sample.

“It is easy to self-collect and so noninvasive—and not irritating; for many already, it is their preferred approach for testing, so we hope to have more saliva-based testing going forward,” Wyllie says.

Below, we share the five most important things you need to know about the SalivaDirect test method.

SalivaDirect uses commonly available laboratory materials and not specialized reagents that have sometimes been in short supply.

“This saves one or two hours of work and removes up to 75% of the costs,” says Nathan Grubaugh, PhD, a Yale School of Public Health epidemiologist, who worked together with Wyllie on the SalivaDirect research efforts. 

And price was top of mind with the researchers—they designed the test so that it would only cost a couple of dollars for the chemicals needed to process it. 

In May 2020, NBA officials contacted the researchers shortly after they posted their initial results online. The basketball league wanted its teams to safely return to competition. For that to happen, they needed a quick and easy way to test players daily. They also recognized a need for this type of test—and for it to be affordable—for the community.

So, the Yale team partnered with NBA teams to enroll up to 500 players and staff in a study called SWISH (Surveillance With Improved Screening and Health) in the summer of 2020 to evaluate how well SalivaDirect could work for healthy, asymptomatic people. The NBA arranged to play its season in a “bubble” on the campus of Walt Disney World in Orlando. Leading up to the bubble, basketball players and staff received routine testing every two days with a combined nasal and oral swab, then had the choice of providing a saliva sample for Yale to study. 

The researchers point out that this kind of frequent testing is ideal to help stop outbreaks in any situation where people cannot maintain six feet of social distancing—this could be especially relevant to essential workers and students returning to school. (The study took place prior to the emergence of Delta and Omicron variants.)

In the summer of 2020, an EUA was issued by the FDA for a SalivaDirect protocol. So, there wasn’t a SalivaDirect kit created for purchase; instead the researchers made the directions and materials needed to create and process the test freely available online. 

But the FDA has since issued an EUA for SalivaDirect unsupervised and at-home collection kits. Tests can be ordered from participating laboratories or suppliers, with specimens returned to the lab for testing. More information on how this process works can be found on the SalivaDirect site.

EUAs are only given during public health emergencies. Even though approval is based on limited data, agency officials agree that the potential benefits would outweigh any potential risks. 

The FDA has granted EUAs for other COVID-19 diagnostic tests, including other saliva tests and at-home nasal swab-based tests, as well as repurposed drugs and medical devices that can be used to fight COVID-19. 

Researchers have validated results of SalivaDirect on different equipment and with easy-to-find reagents. “This flexibility enables continued testing if some vendors encounter supply chain issues, as experienced early in the pandemic,” Wyllie says. 

Results so far have found that SalivaDirect is highly sensitive (this means the test correctly identifies patients who actually have the disease) and is accurate 94% of the time, comparable to results for nasopharyngeal-based tests. 

Recently, research studies have also reported that saliva samples can detect the virus earlier in the course of infection, particularly with the Omicron variant. One December 2021 study, which has not yet been peer-reviewed, demonstrated that saliva was 12 times more sensitive for the early detection of SARS-CoV-2 as compared to a nasal swab. With the emergence of Omicron, saliva is also proving more sensitive for early detection, with high levels of infectious virus detectable in saliva—sometimes for days before being detectable by nasal swabs, explains Wyllie.

“It’s been remarkable watching the journey of saliva in COVID-19 testing,” Wyllie says. “An increasing number of studies are showing the sensitivity of saliva—even before Omicron—at detecting SARS-CoV-2 compared to PCR-based nasal swabs. People can be infectious when levels are only detectable in saliva. If this is to be our dominant variant going forward, then we will want to update our testing methods.”

Last year, Yale School of Medicine researchers released a study showing that high levels of the SARS-CoV-2 virus in a person’s saliva could be a predictor of who will be more likely to develop severe disease, be hospitalized, or die from COVID-19. 

This information could help doctors determine which patients should be treated early with medicines such as monoclonal antibodies, which can decrease the viral load and work best in the early stages of the disease. The study was published on a preprint server that still needs to undergo peer review.

“We discovered that the saliva viral load is a much better correlate of disease outcome than the nasopharyngeal viral load,” says Akiko Iwasaki, PhD, lead author of the study, and an immunologist at Yale School of Medicine.

While the nasopharyngeal swab only looks as far as the nasal passages, detecting the virus in the saliva means that it’s more likely to have infiltrated the lungs, where COVID-19 causes the most serious damage, says Iwasaki. That’s because cilia (hair-like projections) in the respiratory tract regularly move mucus up to the throat where it mixes with saliva, or it can move during a cough.

“The saliva viral load correlates not only with the disease severity, but also with the immune response to COVID-19, and older age, [male] sex, and co-morbidities that have been found to put people at higher risk—essentially every parameter that we've examined,” Iwasaki says.  

Kathy Katella contributed to this article.