Antibody Tests Should Not Be Your Go-To For Checking COVID Immunity

Booster shots against the coronavirus have already started rolling out in the U.S. for some people and millions more could be due for them soon. But as breakthrough infections become more common, many people are wondering in the meantime: Does my immune system have enough firepower to protect me right now?

A natural way to look for an answer would seem to be checking for certain antibodies in your blood that target the coronavirus. These are specific proteins made by your immune cells in response to the vaccine or the virus — proteins that serve as a key part of the body's arsenal in preventing COVID-19.

Unlike other COVID-19 tests that are used to diagnose an active infection, these antibody tests are aimed at finding evidence of your body's immune response to a past infection with the virus, but they can also pick up certain antibodies that your body generated in response to the vaccine. And while the Food and Drug Administration does not currently recommend antibody tests to assess immunity, that isn't stopping some people.

"I know a lot of people, even outside of studies, are just getting their antibody levels done," says Dr. Ghady Haidar, a transplant infectious diseases physician at the University of Pittsburgh Medical Center.

There are dozens of tests on the market that scan blood samples from a blood draw or a finger prick for the presence of these antibodies. Some tests just let you know if you have them — or not. Others can actually give you scores that reflect your levels. You might think that high enough levels of antibodies mean you don't need that booster, right? Eh, not so fast.

While it could be tempting to consider these tests a measuring stick of your immune response — or lack thereof — researchers and doctors say your protection against the virus still can't be boiled down to antibody levels in a simple blood test.

Why tests don't tell the full story

On an individual level, antibody tests can be useful for picking up evidence of a past SARS-CoV-2 infection. They're also helpful to researchers studying the prevalence of the virus across a population or tracking the degree to which antibody levels wane over time. And the decline in antibody levels against the coronavirus among some people who got vaccinated late last year were cited as part of the scientific case for why millions of Americans need booster shots.

But scientists in the field say there's still considerable uncertainty about what these levels of detectable antibodies really mean when it comes to protection. And a lack of standardization among the commercially available tests for antibodies makes it even harder to decipher the results.

"There is no test that will give you that [degree of certainty] at this point," says Gigi Gronvall, a senior scholar at the Johns Hopkins Center for Health Security who has studied serology testing and COVID-19. "There are tests that would show that you've been vaccinated or not, but is that going to be the kind of information you need?"

Maybe not, she suggests. Why? Antibody tests only give one view into the body's collection of defenses against the coronavirus. In fact, it's just a subset of antibodies, made in response to the virus or a shot of the vaccine, that neutralize the spike protein on the virus. The spike protein is what enables the coronavirus to break into cells and replicate.

"We have a mix of antibodies. Some of them are very good and protective. Some are not as protective," and each person will have their own mix of these different types of antibodies, says Ali Ellebedy, an immunologist at Washington University School of Medicine in St. Louis who's studying the antibody response to the coronavirus.

A key unanswered question for researchers like Ellebedy is just how many of these neutralizing antibodies are needed to block the virus?

Studies do show all three available vaccines in the U.S. — the shots from Pfizer, Moderna and Johnson & Johnson — can successfully prompt people to produce neutralizing antibodies for the coronavirus variants, including delta. Natural infection with the virus also leads the immune system to produce antibodies that can disarm the virus, though doctors still recommend you get vaccinated even if you've had COVID-19 in the past, because the shots bolster your immune response, including your antibodies. But Ellebedy says that having detectable antibodies from a blood test six months after vaccination "only means that your immune system mounted a successful response then and that you have immune memory."

While scientists have generated a "ton of data" on which antibodies are best at neutralizing the virus, Ellebedy says, the available antibody tests are not designed to specifically pick up whether you have enough of these protective antibodies, especially in the face of evolving variants.

And don't forget the immune system is more than just antibodies, so even with low detectable levels in your blood, you're not defenseless. "Antibody tests — it's really probing just one part of your immune system," says Elitza Theel, who directs the Infectious Diseases Serology Laboratory at the Mayo Clinic.

Your immune system really kicks into action if your body encounters the coronavirus. At that point, it generates new antibodies to block the virus and taps another line of defense — called T cells — which clear out the infected cells that have been converted into factories where the virus can multiply.

If you do get an antibody test, can you learn anything from it?

Yes, as long as you don't expect it to give you a straightforward answer for how well-protected you are from catching the virus. The FDA and the Centers for Disease Control and Prevention recommend against using antibody tests for this purpose, but it's understandable that Americans are looking to these widely available tests for some indication of their immunity, especially given the growing concerns about declining efficacy of the mRNA vaccines over time. So what sort of legit information could you glean from the results?

Dr. Nicole Bouvier says it's reasonable to look at how your results fit into the range of values of a particular test, to get a sense where you fall relative to others who've taken it. Lab companies may also be able to tell you the average level of antibodies of someone who had a coronavirus infection and recovered.

"That can give you a benchmark for the immune response to natural infection, and then you can sort of gauge your vaccine response against that," says Bouvier, an associate professor of infectious diseases and microbiology at the Icahn School of Medicine at Mount Sinai.

The tests may give you numerical readings that indicate the level of antibodies in your blood that bind to specific SARS-CoV-2 proteins. "What we're basically learning is that the higher your number is, the more likely you are to be protected," Bouvier says, "and that you don't actually need a super, super high number in order to be protected." But this rule of thumb is based on large studies and doesn't necessarily hold true on an individual level.

The bottom line is that even doctors who are studying this topic don't know what these antibody readings actually say about your immunity, says Haidar of the University of Pittsburgh Medical Center, who is running a study on coronavirus antibody response in immunocompromised individuals.

"We don't know what the optimal antibody level is that correlates with protection," he says.

For example, Haidar says it's clear that immunocompromised patients may not have as robust an immune response to the vaccine, and that looking for the presence of antibody levels can hint at their level of protection. But even this can be misleading — because some research suggests that detectable antibodies from those patients still "may not be able to prevent infection as well as antibodies from people who are otherwise healthy."

Haidar concedes that if someone has no detectable antibodies on the test, "even though they may have some protection from T cells — and we don't have a full understanding of what this actually means — I can tell you that they are likely not as protected as someone who, let's say, has an antibody level of 1,000."

Only complicating the picture for consumers is that the tests on the market are not standardized. They can have varying degrees of sensitivity and look for different antibodies.

Some antibody tests sold commercially detect certain antibodies that are only generated in response to the actual virus. Getting a test that looks for these other antibodies (antibodies that target the nucleocapsid protein, for example) could lead someone who is vaccinated to get a negative result and falsely think they are not protected.

Despite all these caveats, the idea of a blood test that can eventually give consumers a reliable indication of their immunity is not far-fetched. "We have correlates of protection for other vaccine-preventable diseases like measles and hepatitis," says Theel. "But we're just not there yet with COVID." [Copyright 2021 NPR]