A Next-Generation Coronavirus Test Raises Hopes And Concerns

States clamoring for coronavirus tests in recent weeks have been talking about two different types. First, there's a PCR test that detects the virus' genetic material, so can confirm an active infection. And then there's an antibody test, which looks at the body's reaction to that infection, so is useful in identifying people who have been infected with the virus in the past.

Now, there's a third kind of test under development to help fight COVID-19 that homes in on proteins that stud the virus's outer surface; it, too, detects an active infection. Known as an antigen test, this one could offer a much easier and more widely available alternative for diagnosis than the PCR test, proponents say, though some other scientists remain concerned about the test's reliability.

"We have to have a breakthrough innovation in testing," Dr. Deborah Birx of the White House Coronavirus Task Force said recently on Meet the Press in her most recent pitch for antigen tests. "We have to be able to detect antigen rather than constantly trying to detect the actual live virus or the viral particles itself."

Though there are no authorized coronavirus antigen tests on the market yet, several companies are already working on them, including one that has started seeking a stamp of approval from the Food and Drug Administration.

"It's very exciting," says Lee Gehrke, a microbiologist at Harvard and the Massachusetts Institute of Technology who is involved with E25BIO, a Cambridge, Mass., company developing the test. "It could change the landscape for testing."

OraSure Technologies Inc. of Bethlehem, Pa., is also developing an antigen test that would enable people to test themselves at home from a saliva sample.

"Having a rapid antigen — in-home — self-test will help both combat the virus and also individual fear," says Stephen Tang, the company's chief executive officer. "It actually gives the individual a bit of control and understanding — whether they're infectious and whether family members are infectious. So I think it starts to get us back in a mindset where we can control our destiny."

Public health experts agree that such a test could be very helpful.

"Rapid antigen tests would be valuable because of their speed," Tom Inglesby, who directs the Johns Hopkins Center for Biosecurity, wrote in an email.

But Inglesby and others caution that any antigen tests would have to be carefully vetted to make sure they're accurate. Relaxed oversight by the FDA recently has raised concerns about the reliability of some other kinds of tests — such as antibody tests — which are being marketed aggressively by some companies with unverified claims.

When used to look for other types of infections, such as testing for the flu, or for strep in someone with a sore throat, antigen tests have tended to miss more infected people than the PCR tests for coronavirus typically do, experts say.

"We know an awful lot about the performance of antigen detection tests," says Frederick Nolte, who heads testing at the Medical College of South Carolina. "And we know that that sensitivity leaves a lot to be desired."

Generally, antigen tests tend to miss about 15 to 20 percent of infections, Nolte and others say, and that's likely not good enough for many uses of a diagnostic test for the coronavirus.

"If you're using this test to screen people to make sure that they're not infected, and that they go back to work or things like that, then you'd be giving people the message that they are not infected when actually they are — and therefore transmitting the new coronavirus," says Jesse Papenburg, an infectious disease expert at McGill University.

The tests currently used to see if people are actively infected with the virus are sophisticated molecular tests that can spot its genetic material in specimens swabbed from inside peoples' noses and throats. Most use the technique known as polymerase chain reaction — PCR — to generate and analyze millions of copies of genetic sequences from the virus.

But those tests require sophisticated equipment, highly trained technicians and complicated processes that use specialized chemicals; those strict requirements of PCR tests, and problems in reliably meeting them, have all contributed to the testing shortage.

Widescale testing is considered crucial for determining the scope of the pandemic, bringing it under control and keeping large new outbreaks from occurring. Testing enables public health authorities to spot new infections quickly so patients can be isolated and so anyone they might have had contact with.

Typically, antigen tests are much easier and less expensive to manufacture and simpler to perform than either PCR tests or antibody tests. The same technology is used in pregnancy tests.

"It looks very much like a pregnancy test. And they're very simple. They don't require special chemicals or training to use them. And they can give you a read out in about 15 minutes or so," says Gehrke, one of the collaborators on the E25BIO test.

Gehrke says his company's test appears to be very accurate when evaluated with samples of the virus in the lab.

"The difficult question — and the one we want to ask — is how well does it perform on samples from real patients," Gehrke says.

Papenburg questions whether antigen test could ever be as reliable as the genetic tests because, unlike those PCR tests, they can't produce large quantities of the target proteins — so might be more likely to miss an infection.

Tang says OraSure is also conducting careful studies to ensure the company's test would be reliable — able to not only detect an infection with the novel coronavirus, but to quickly and accurately discern it from other coronaviruses, such as those that cause the common cold.

"Our aiming point for our rapid antigen test is to make it highly sensitive and highly specific," Tang says, though he acknowledges it remains to be seen how the test will compare to the molecular tests. It could turn out the antigen test's results would have to be confirmed by the PCR tests, Tang says.

Another company, Mologic Ltd. of Bedfordshire, UK, is also developing an antigen test and hopes to get it approved by June, according to Fionna Tod, a company spokeswoman. The test would produce results in 10 minutes and would sell for about $1, she says, which could be very helpful in less affluent parts of the world.

In an email, the company's medical director, Joe Fitchett, noted that genetic tests often use samples gathered through an uncomfortable procedure that involves swabbing deep into the nose.

"PCR tests using nasal swabs can be deeply uncomfortable, and poor technique is well-documented to lead to false negatives," Fitchett says. "On the other hand, saliva that can be deployed in a rapid antigen test and could offer better, more user-friendly performance — that will be critical for a self-test."

During a briefing Wednesday announcing a $1.5 billion effort to speed the development of new coronavirus tests, National Institutes of Health Director Frances Collins said it could be possible to develop reliable antigen tests.

"While traditionally antigen-based tests have lower sensitivity and specificity than do nucleic acid tests, I don't believe there's any law of physics that says that has to be the case," Collin said.

[Copyright 2020 NPR]