There is a universe of ways to get tested for COVID-19, and each has its pros and cons. Most, however, require a medical professional to insert a long, flexible swab up your nose to sample the back of your throat in an invasive, painful and unpleasant procedure. It’s reliable, yes, but not the most encouraging way to convince people to get tested.
Saliva-based tests are likely much more welcome. Most people can spit into a container at home and so don’t need to go to a health clinic or drive-through testing facility—a plus when an infectious disease is roaming the world—and it doesn’t involve any discomfort. Adding this more convenient testing option, which also happens to be less expensive than other tests, could vastly increase testing rates and make it safer to open schools, workplaces, restaurants, shops and any other venue where large numbers of people congregate.
The U.S. Food and Drug Administration gave emergency use authorization (EUA) to the first saliva test for COVID-19 in April, but it required that people still spit into a specialized container with a dedicated solution in the presence of a health care professional. The next authorization, in May, was the first to allow people to provide their samples at home. The EUA only applied to tests that were conducted by its developers at Rutgers University; samples had to be collected in special tubes that the scientists sent to people and had to be analyzed at the Rutgers Clinical Genomics laboratory.
More recently, however, the FDA issued an EUA for a test called SalivaDirect, which doesn’t require special (and potentially expensive) containers—any standard sterile one that costs a few cents will do. Labs can apply for authorization to process SalivaDirect samples, and once in the lab, researchers also don’t need to use special chemicals to extract the virus’ genetic material. These so-called reagents are used in other tests as well, which means they have been in short supply in the past few months as testing demand surged. SalivaDirect’s EUA still requires people to spit in the presence of a health care professional, but the company has requested the FDA expand that authorization to allow people to collect their samples at home.
SalivaDirect’s co-developer, Anne Wyllie, associate research scientist in epidemiology at Yale School of Medicine, says that while intuitively simple, saliva testing for a virus like SARS-CoV-2—the virus that causes COVID-19—isn’t necessarily easy to execute. Wyllie has been working with saliva as a testing sample for most of her career.
“Saliva itself is a newer diagnostic method, and a lot of people don’t know how to work with it, are scared to work with it, or not sure how to work with it,” she says. “Just because a protocol is working with swabs doesn’t mean the same protocol will work with saliva.”
She notes that collecting samples with swabs is more standardized, and more people are trained and comfortable with the method’s reliability. That’s not yet true of saliva, and explains the reticence to rely on it early in the COVID-19 pandemic. There was also the fact that, in the early months of the outbreak, researchers weren’t sure saliva would be a good place to look for the virus, since most of the disease they were seeing involved the respiratory tract. Research since has shown that the virus is indeed in the saliva, and can be a convenient way to test for SARS-CoV-2.
“Some studies show that saliva is less reliable than nasopharyngeal swabs, and some studies show that saliva is better,” says Michael Mina, assistant professor of epidemiology at Harvard T. H. Chan School of Public Health. “The jury is still out on the real role of saliva tests. But what we do know, is that there is potential for it. It can be a very powerful tool.”
Wyllie adopted her method of processing saliva samples to make it applicable to SARS-CoV-2, and made it available open source for any researcher to use. “As other people … shared it, we started to see more people have more success with it because they learned how to work with it,” she says.
Like the PCR test—the current gold-standard method that looks for traces of SARS-CoV-2 genes and amplifies them—SalivaDirect also detects viral genetic material. But instead of extracting this genetic material from the sample using a chemical process, SalivaDirect relies on an enzyme to heat up the sample, with the same result of pulling out the viral genes. That helps scientists avoid any backlogs with in-demand agents.
Wyllie and her team tested the first version of their saliva test on samples collected from patients and staff at Yale-New Haven Hospital and compared them to standard PCR test results. In a pre-print study published in early August, they showed 97% agreement between results from the two tests. They also determined that because the test did not require special collection tubes, and if people collected saliva themselves, the cost could run as little as $1.29 per test.
Those results attracted the National Basketball Association, which reached out as the league was planning to establish its bubble and saw saliva testing as a way to more regularly test players and staff. The NBA and Wyllie’s team worked together to further refine the test and produce additional data which was eventually submitted to the FDA. The league’s health staff, which already had nasopharyngeal swabs from players, coaches and staff joining the NBA’s bubble, also collected saliva samples so Wyllie and her team could compare results from the two methods. Those results showed that saliva could be as good a source for detecting SARS-CoV-2 as the back of the nose and throat, and that the unique method involved was also a reliable way for picking up the virus.
In addition, Wyllie and her team published more findings in the New England Journal of Medicine from ongoing studies among hospitalized patients and health care workers that supported the validity of the saliva test. They found that 81% of saliva samples tested positive for the virus one to five days after diagnosis compared to 71% of the nasopharyngeal samples, suggesting saliva might be a more accurate representative than mucus for whether or not the coronavirus is still somewhere in the body.
“Saliva represents the collection of all oral fluids, from the salivary glands, nasal drip and even mucosal clearance from the lungs,” Wyllie says.
Given that, she is currently also exploring whether saliva tests can be used to find the virus in people who have COVID-19, but don’t show any symptoms—which some experts estimate could include up to 40% of infected people. Because they don’t feel sick, these asymptomatic people might be spreading the virus without knowing it. Wyllie is continuing to work with staff who are part of the NBA bubble to determine if saliva testing can be a way to help detect asymptomatic people sooner and help them to isolate and lower their chance of transmitting COVID-19 to others.
Expanding testing to more asymptomatic people will depend in large part on how easy the test is to conduct—do-it-yourself and home-based tests will probably be necessary. In addition to saliva-based tests that require people to spit into tubes, researchers at other companies are also looking into paper strips that can read saliva samples. Decision Diagnostics, a California-based company that is the leading manufacturer of diabetic test strips, for example, has developed a saliva-based strip test for COVID-19 that is being tested in South Korea.
Wyllie hopes that SalivaDirect will make testing more accessible by making it possible for more smaller commercial labs to conduct COVID-19 testing, since the saliva test doesn’t require the expensive equipment and personnel that other tests do. While scientists can run thousands of PCR tests at one time time, that method requires specialized machines that are generally only available at large commercial testing labs and other well-resourced lab facilities. SalivaDirect could be performed by smaller labs that could alleviate some of the burden from the larger labs that have been experiencing delays in turning test results around.
“We are trying to work with smaller local labs that want to get up and running to support schools, community groups, universities and colleges,” says Wyllie. “The more testing we do, the more that leads to less transmission and hospitalization, and also frees up larger diagnostic testing labs from processing patients samples as well.”
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Contributor: Alice Park