Not All COVID-19 Antibody Tests Are Safe or Accurate, According to Health Experts

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In early April, the United States Food and Drug Administration (FDA) approved the first COVID-19 antibody test amidst much fanfare from the scientific community. The hope was to use this type of blood test (which is different from tests for the virus itself) to identify people who have already been exposed to SARS-CoV-2 (aka the novel coronavirus that causes the disease COVID-19) by testing their blood for the presence of COVID-19-specific antibodies—proteins produced by white blood cells as a direct response to the novel coronavirus.

Knowing who has been exposed to the coronavirus has huge implications for fighting the pandemic. Considering an estimated 25 percent of individuals who contract SARS-CoV-2 are asymptomatic (and thus likely don't ever get tested for the virus), and a large percentage of cases (about 80 percent) are considered mild, an antibody test could give public health officials a better understanding of how many people truly have had COVID-19. Even more exciting: People who have been exposed to the coronavirus might also have some immunity to it, thanks to the antibodies their immune system created to fight off the virus. (Emphasis on might—we don't know enough about the virus yet to know whether a person would be totally immune or just less vulnerable to future infections, or how long that immunity might last.)

In theory, this could be game-changing for health-care workers and others on the front lines fighting the pandemic, Rand McClain, DO, chief medical officer of Live Cell Research, previously told Well+Good. “If we can identify that they’ve already inoculated the virus, and are therefore [potentially] immune, then [the fear of getting sick] doesn’t have to add stress to everything else is going on,” he said. “We can put those people on the front lines, and those who don’t have the antibodies we can choose to be more careful with.” Companies like Amazon and General Motors have also talked about doing wide-scale testing of their employees to see who has already been exposed and thus is potentially safe to come back to work—an appealing idea to many during a massive economic collapse.

There's also been talk of using people who have recovered from COVID-19 for plasma donations for people who are critically ill—effectively gifting immunity to those most at risk of dying from the virus. (The Red Cross is seeking such donations now.) Antibody testing could widen the field of potentially eligible donors by identifying even more people who have had the virus.

However, in recent weeks, the medical community has come to grips with the fact that many of the publicly-available antibody tests aren't living up to their promise. The antibody tests mass-ordered by the UK turned out not to be able to test for the novel coronavirus,  while $100,000 worth of tests ordered by the University of Washington from China had to be recalled because they were contaminated with a bacteria. The Centers for Disease Control and Prevention (CDC) even updated its guidance on these tests over the weekend, saying that they might be providing false positives up to 50 percent of the time, depending on how prevalent the coronavirus is in a given area. So what went wrong?

Are COVID-19 antibody tests accurate? It depends

Obviously, the massive potential of these tests hinges upon their ability to accurately identify COVID-19 antibodies (first, an antibody called IgM which appears when your body starts fighting a new infection, and second, a version of IgG, which created later to fight the specific invader), and we're not quite there yet.

According to Dr. McClain, what makes an antibody test "accurate" really comes down to two factors: its sensitivity and its specificity.  Sensitivity refers to a test's ability to measure a "true positive" (someone who is most likely immune to COVID-19) while specificity is defined in this case as a test's ability to identify immunity to this particular strain of coronavirus (SARS-CoV-2)—and not immunity you may have developed from another form of the virus (like 229E, NL63, OC43, and HKU1) at a different stage of your life. A test lacking in both factors will yield an inaccurate—and potentially life-threatening-result.

"This can be potentially extremely dangerous," says George Declos, MD, PhD, respiratory disease and occupational medicine specialist at the University of Texas. "Not only because [a bad test] gives misinformation, but because it may trigger actions on the part of employers, and possibly even health-care providers, to act on the basis of a positive result that is inaccurate." For example, if someone goes back to work after getting a false positive from a bad antibody test, Dr. Declos says, they're now being put in a dangerous situation where they could actually get infected (because no antibodies = no immunity at all.)

"This can be potentially extremely dangerous. Not only because [a bad test] gives misinformation, but because it may trigger actions on the part of employers, and possibly even health-care providers, to act on the basis of a positive result that is inaccurate." —George Declos, MD, PHD

Yet despite the very real risks of faulty tests, there isn't a ton of oversight right now on what's going to market. When the FDA issued emergency use authorizations  ("EAUs") for four COVID-19 antibody tests earlier in the month, Dr. McClain says that the Secretary of Health and Human Services also issued a policy stating that, "circumstances exist justifying the authorization of emergency use of in vitro diagnostics for the detection and/or diagnosis of the novel coronavirus." Meaning, so long as the company wrote a letter to the FDA promising to adhere to the rigorous requirements of the tests put in place by the department, they wouldn't need to be vetted.

According to Dr. McClain, many companies are staying true to their word and creating tests that follow the FDA's guidelines down to the last detail. A number of them have either not submitted letters to the FDA, however, and still more are advertising that they're "approved by the FDA," when they technically are not. "They are registering with the FDA through a letter saying, 'We promise you the tests have been validated.' So if it does come out that they're not, in fact, validating this testing, they're going to get a pretty good spanking," he says.  So, of course, the findings from these tests cannot be trusted in the same way as the FDA-vetted Mount Sinai Laboratory test or the Ortho Clinical Diagnostics, Inc. test—because there's been no third-party confirmation that these tests are truly effective.

FDA commissioner Stephen Hahn said in a statement that the department is now in the process of investigating and warning companies that are issuing poorly manufactured tests, along with the help of the Center for Disease Control and Prevention (CDC) and the National Institutes of Health (NIH). "When we become aware of these issues, we have and will continue to take appropriate action against firms making or distributing unvalidated tests or those making false claims, such as issuing Warning Letters requesting that companies stop their unlawful promotion and detaining and refusing fraudulent test kits at the border," he said.

Hopefully, stricter regulations will deliver the antibody test back to its original status as a source of hope—and not one of confusion—says Dr. McClain. And more importantly, a larger crop of dependable tests will generate data that are easier to interpret, learn from, and implement.

My workplace or doctor offered me an antibody test—how can I vet it myself?

Despite the fact that companies like Amazon and General Motors are looking into the idea of antibody testing their employees, both Dr. Declos and Dr. McClain agree: We're nowhere near ready to use antibody tests as a way to end the workforce's remote status. The science just isn't there yet.

"If you are thinking about having people to return to work based on an assumption that just because they have antibodies means that they are protected from infections, and it turns out not to be the case when the science is reviewed, that is concerning because you're putting people in harm's way unnecessarily," says Dr. Declos. "I think antibody testing is a good thing, but I think jumping the gun and making use of testing before the science is there can be extremely dangerous."

If you are given the opportunity to take the antibody test through your place of work, there are a few ways to vet it yourself. The most obvious? Call your doctor. "If I'm the patient, that's the best way. A doctor is supposed to go through this process and vet [the test], and has the tools, presumably, to do so," says Dr. McClain. The next best place to go is the FDA's website, which lists out all of the tests as well as their status. If you don't see the test distributed by your employer on the list, take your results with a grain of salt. (Oh, and if a test is costing you a mere $5, you can go ahead and write it off as fake.)

The path forward for antibody tests

Dr. McClain is optimistic that $484 billion relief bill working its way through Congress this week, which promises to provide money for COVID-19 testing, will also pave the way for a larger sample size of people who have received the highest quality antibody tests.

"A large amount of testing would be required to get a handle on this virus," says Dr. McClain. "We need a representative sample in this country to figure out a range of how many people are infected, how many people have symptoms and don't, and how many have died. Right now, we have what would be considered a very biased sample in that we really only have information on the people we know are infected, and particularly those with severe disease."

With this information in hand, he believes it would be easier to make smart, calculated decisions about how long the country needs to stay shut—and when it's okay to open back up.  "All this information is still not sufficient to get our arms around the virus. We have statistics which tell us that fewer people are dying now. About the virus itself, though, we know very, very little still, because we don't know how many people are infected now."

"We need a representative sample in this country to figure out a range of how many people are infected, how many people have symptoms and don't, and how many have died." —Rand McClain, DO

Researchers from the University of Southern California and Los Angeles County Department of Public Health recently tried to pool a smaller model of the "representative sample" Dr. McClain is referring to by using the antibody test results of 3,330 participants to determine how many people in LA had been exposed to the virus. The study indicated that between 2.8 percent and 5.6 percent of those tested may have been infected in early April. And although the study has been criticized for certain biases, it does shed light on the kind of data that could be made available in a nationwide study conducted with sound, FDA-approved tests.

The first-generation HIV antibody testing (introduced in 1985) produced false-positives and underwent five more iterations over 30 years until it became the accurate test it is today. Here's hoping that in 2020 we can use knowledge from past experiences (and common sense) to make COVID-19 antibody testing efficacious faster and more efficiently.

This story was originally published on April 22, 2020. It was updated on May 27, 2020. 

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