For months, public health experts have been eagerly watching the companies developing spit tests for the coronavirus that could be used at home, producing results in a matter of minutes.
If these rapid tests worked, as many news articles have pointed out, they could greatly expand the number of people tested. Some experts have said they could perform as well as a vaccine in curbing the spread of the virus. But so far, the technology is not panning out as some have hoped.
E25Bio and OraSure, two companies pursuing rapid at-home coronavirus tests, have abandoned efforts to use saliva in their products. Their tests, which detect pieces of coronavirus proteins called antigens, will for now rely on shallow nose swabs.
“If I was placing a bet — which I am, because I’m leading an antigen-based testing company — I would say it’s going to be very difficult for antigen-based testing to work on saliva samples,” said Bobby Brooke Herrera, an E25Bio founder and its chief executive. The notion that the virus sets up shop in the mouth and produces enough antigen to be picked up by today’s technology, he said, “is far-fetched.”
The two companies pursued saliva (or “oral fluids,” in the case of OraSure) for months in the hopes of their tests being more comfortable than swabs, some of which go painfully deep into the nose, and less reliant on supply chains that have caused long delays for laboratory tests.
“There’s nothing more convenient than spitting in a tube,” said Dr. Valerie Fitzhugh, a pathologist at Rutgers University.
But as they continued to tinker with their tests, researchers at both E25Bio and OraSure found saliva’s performance to be more lackluster than anticipated. “This was a result of optimization studies,” said Stephen Tang, OraSure’s chief executive. A saliva antigen test is still theoretically possible, Tang added. But after comparing the amount of coronavirus antigen found in the nostrils and throat, as well as different parts of the mouth, including the cheeks, gums and tongue, “we decided to optimize around the nasal cavity,” he said.
Despite a deluge of data on saliva’s benefits, it’s relatively new to the testing scene. No fully government-approved test for a respiratory pathogen has ever used spit. And there’s still no consensus on how well saliva works for detecting the coronavirus, compared with the fluids obtained by nose swabs. Studies comparing the amount of virus in the two sites have produced conflicting results.
Spit also differs vastly among people, and can even change over the course of a single day. “We’ve all noticed that there is variable performance,” said Sarah Jung, scientific director of clinical microbiology at Children’s Hospital Colorado.
Both E25Bio and OraSure plan to seek authorization from the Food and Drug Administration to sell at-home antigen tests using nose swabs instead of spit, a technique similar to the one used by the Abbott antigen test that takes about 15 minutes. The E25Bio test would require people to swab their nose, stir the sample into a chemical soup, apply the mixture to a paper strip and wait up to half an hour for bands to appear. E25Bio’s test picks up on about 80% of the infections that ultrasensitive laboratory tests detect — the FDA’s bare minimum for a regulatory greenlight. OraSure declined to give any details about its test’s methodology or accuracy.
Saliva does seem to be working when used in laboratory tests known as PCR, which look for bits of the virus’s genetic material, or RNA, rather than antigens. PCR tests detect minute amounts of coronavirus RNA, making them far more sensitive than antigen tests. Research teams at Rutgers and Yale have been granted emergency authorization for these spit PCR tests.
At the University of Illinois, some 10,000 of the institution’s in-house PCR tests are performed each day on saliva from students, faculty and staff members — roughly 1% of the nation’s daily tests. Standard PCR tests, however, take hours to run and are subject to shortages.
Other scientists, like Dr. Zev Williams of Columbia University, are working on variants of rapid saliva tests that, like PCR, detect RNA, but don’t require expensive laboratory machines. His team’s prototype takes 45 minutes. It uses an array of portable equipment, including two tissue-box-size heaters.
That’s too bulky and expensive for at-home testing. But he said the test could be deployed in places where crowds gather. His team has submitted an application for emergency approval from the FDA. In the meantime, they’ve partnered with Sorrento Therapeutics to scale up production.
The Columbia saliva test relies on a technique called LAMP that’s generally faster but a bit less accurate than PCR. The spit sample is briefly boiled and mixed into a cocktail of chemicals that then gets incubated at 145 degrees Fahrenheit for half an hour. The latest data shows the Columbia test performs as well as a laboratory deep-nose swab test more than 96% of the time, even when using saliva from sick patients who gave messy samples.
“Even if there was food or blood, we took it,” Williams said. That wouldn’t fly with most other saliva tests in use, he said, which ban eating, tooth-brushing and even gum chewing for about an hour before.
Another saliva LAMP test is being tested by David O’Connor at the University of Wisconsin-Madison. Their technique bears many similarities to the Columbia test but takes slightly longer and involves extra steps. Early trials have gone well, O’Connor said.
But saliva LAMP tests face their own hurdles. Saliva tends to clump and stick, and can be a difficult substance to handle and transfer from tube to tube, said Jennifer Dien Bard, director of the clinical microbiology and virology laboratory at Children’s Hospital Los Angeles.
“To me,” Dien Bard said, “something like this might still belong in a lab.”
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