When the coronavirus pandemic broke out across the country, healthcare providers and scientists used the standard method for detecting respiratory viruses – sticking a long swab up the nose to obtain a sample.
But the difficulty in carrying out these large-scale tests soon became apparent.
Among other things, many people were reluctant to undergo the unpleasant procedure, called a nasopharyngeal swab. It can only be done by trained healthcare workers, putting them at risk of infection and increasing costs. And the swabs and chemicals needed to test for the virus became scarce.
In some jurisdictions, such as Los Angeles County, the collection of oral saliva swabs and sputum. The process was supervised, in places where it was not necessary to get out of the car, by trained personnel dressed in personal protective equipment. Meanwhile, researchers began looking for cheaper and easier alternatives, including dropping saliva into a test tube.
But the transition has not been immediate. Regulators and scientists are often wary of new, untested technology, and have an understandable bias toward well-established protocols.
“Saliva is not a traditional diagnostic fluid,” said Yale microbiologist Anne Wyllie, part of a team whose saliva-based test, called SalivaDirect, received authorization for emergency use from the Food and Drug Administration in August. Medications (FDA). “When we were hit by a virus that came out of nowhere, we had to respond with the tools available.”
Eight months after the onset of the pandemic, the saliva test is gaining traction and tens of thousands of people across the country undergo these tests daily. However, saliva tests represented only a small percentage of the more than 900,000 tests performed daily, on average, at the end of September.
Yale facilitates its protocol openly and has recently designated laboratories in Minnesota, Florida and New York to perform the test.
In addition to the Yale test, the FDA has cleared others for emergency use, including versions developed at Rutgers University, the University of Illinois at Urbana-Champaign, the University of South Carolina, and SUNY Upstate Medical University. Another advance, a home saliva test, could also receive FDA clearance.
Since the beginning of the pandemic, the Trump administration’s approach to testing has been hampered by errors and controversy.
As a key health agency during an unprecedented emergency, the FDA’s effectiveness depends on the public’s trust in how it balances the need for speed in the authorization of innovative products, such as saliva tests and vaccines, with the assurance of safety and efficacy, explained Ann Keller, associate professor of health policy at the University of California-Berkeley.
“Obviously, you want to add new tests quickly to address the emergency, but you still need to maintain the standards,” Keller said. Pressure from the White House on the FDA has complicated the agency’s efforts by undermining its credibility and independence, he added.
Respiratory viruses colonize areas of the nasal cavity and in the back of the throat. In addition to the nasopharyngeal approach, nasal swabs obtained with shorter and less invasive swabs have been shown to be effective for coronavirus and have been carried out, although they also generally require the participation of a healthcare worker.
The millions of rapid tests that will be distributed across the country, according to a recent White House announcement, are based on nasal swabs.
In the first months of the pandemic, some studies reported significant levels of the virus in oral secretions. In a Hong Kong study published in February, for example, the virus was found in the saliva of 11 patients out of 12 with confirmed coronavirus infection.
In Los Angeles, which began using the oral swab test in late March, more than 10,000 samples are collected a day, said Fred Turner, CEO of Curative, the company that developed it.
Turner sees an advantage in the oral swab strategy. The self-examination procedure takes only 20 to 30 seconds, while producing enough saliva for the test can take a person two to three minutes, and sometimes longer, he said. “It may not seem like much of a difference,” Turner said, “but it is when it comes to getting 5,000 people through a testing site.”
Curative’s three labs process tens of thousands of tests from jurisdictions across the country in addition to Los Angeles, Turner said. A test developed at SUNY Upstate Medical University, which is expected to be available from New York state laboratories, also uses an oral swab.
For the Curative test, a healthcare worker supervises the collection of the sample; reminding people to cough to get fluids, for example. When researchers at the University of Illinois launched what they called the “Manhattan Project” to develop a saliva test in mid-June, they expected people to visit a collection site, spit into a test tube, seal it, and put it down. leave without the help of a healthcare worker.
The university is currently testing more than 10,000 people a day on its three campuses and trying to expand access to communities across the state and nation, said chemistry professor Paul Hergenrother, who led the research team. investigation. Like Yale’s similar test, it has been made available to other labs for free. The University of Notre Dame in Indiana recently adopted it.
Like tests that use nasopharyngeal swabs and other types of nasal swabs, these saliva tests are based on PCR technology, which amplifies small amounts of viral genetic material to facilitate detection.
Both the Yale and the University of Illinois tests have simplified the process by eliminating a standard intermediate step: extraction of viral RNA. Their protocols also do not require Viral Transport Medium, or VTM (the chemicals generally used to stabilize samples after collection).
“You don’t need swabs, you don’t need healthcare workers, you don’t need VTM, and you don’t need RNA isolation kits,” Hergenrother said.
In the statement, published in the New England Journal of Medicine, the Yale team reported that they detected more viral RNA in saliva samples than in nasopharyngeal samples, and that a higher proportion of saliva tests showed positive results up to 10 days later. of the initial diagnosis.
The National Basketball Association (NBA) contributed $ 500,000 in support of the Yale project, said David Weiss, vice president of the NBA. He said the Yale team’s decision to eliminate the RNA extraction process, which separates genetic material from other substances that could complicate detection, required adjustments but did not compromise the value of the test.
“Any molecular test that involves RNA extraction is going to be, almost by definition, more sensitive, but it will also be more expensive and time consuming and will use supplies that are in short supply,” he explained. “If we are looking for screening tests to open schools and nursing homes, a test that is still very sensitive and much cheaper is an important innovation.”
Prices for coronavirus tests vary widely, topping $ 100. Tests based on the Yale or University of Illinois protocols, which require inexpensive materials, could be available for as little as $ 10.
Curative’s testing service, which includes sample collection and transportation, as well as the lab portion, averages about $ 150 per test, depending on volume; said Clayton Kazan, medical director for the Los Angeles County Fire Department, which uses the tests.
Despite advances in sample collection, tests using PCR technology – polymerase chain reaction – still require laboratory processing. Researchers have been investigating other approaches, including saliva-based antigen tests, that could be self-administered at home and would provide immediate results. (While PCR can detect coronavirus genetic material, antigen tests look for viral proteins that can signify an infection.)
At least one company has announced that it is seeking authorization for emergency use of a saliva antigen test, although two others have dropped plans to develop their own versions as unfeasible, according to The New York Times. Meanwhile, scientists at Columbia University, the University of Wisconsin, and elsewhere are investigating the use of saliva with other types of rapid test technology.
“There’s a lot of interest” in a saliva test at home, said Yvonne Maldonado, chief of pediatric infectious diseases at Stanford University School of Medicine.
“People are eager to have access to a pregnancy kit type test,” he said. “Basically you could send people a small package with little strips, every day you take out a strip and put it under the tongue.”
KHN (Kaiser Health News) is a non-profit news service that covers health topics. It is an editorially independent program of KFF (Kaiser Family Foundation) that is not related to Kaiser Permanente.