Antibody Testing After Getting the COVID-19 Vaccine: What to Know If You’re Immunocompromised

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There are many questions that come up if you’re thinking about getting an antibody test after the COVID-19 vaccine: What will the results tell me? Is there a certain kind of test I should get? Is it worth it? If you’re immunocompromised because of an autoimmune condition or taking immunosuppressant medication and anxious to know if the vaccine “worked,” those questions only multiply.

However, there is still a lot that experts don’t know about how the vaccine works in immunocompromised patients, how to interpret the results of antibody tests after you get vaccinated against COVID-19, and what steps could be taken if you didn’t confer enough protection.

That’s why the U.S. Centers for Disease Control and Prevention (CDC) and the American College of Rheumatology (ACR) do not recommend getting an antibody test after receiving the vaccine to assess immunity.

“The risk [for immunocompromised patients] is that you may be operating under the false belief that you’re protected, and you might not be,” says rheumatologist Jeffrey Curtis, MD, MPH, a Professor of Medicine at the University of Alabama at Birmingham who led the task force that created the ACR COVID-19 Vaccine Clinical Guidance. “But if an antibody test comes back with a certain number, nobody knows what that means.”

In other words, if an antibody test result were to indicate that you had antibodies after the COVID-19 vaccine, that doesn’t mean you can assume you’re fully protected. “If you adopt less preventive health measures as a result, that’s a risk,” says Dr. Curtis.

On the other hand, you may be worried if your antibody test doesn’t show a high level of antibodies — but it may not be revealing the full picture.

Many people are confused about which antibody test to get, plus antibody tests only measure one specific component of the immune system when multiple parts play a role in fending off COVID-19, says infectious disease physician Amesh A. Adalja, MD, a Senior Scholar at Johns Hopkins Center for Health Security.

“We don’t want people overly panicked thinking they’re not protected because the antibody test didn’t turn out the way they wanted,” Dr. Adalja says.

Here’s everything you need to know about what antibody tests can — and can’t — reveal after you receive the COVID-19 vaccine, and why it appears best to hold off until more is known about antibody testing.

Understanding the Different Types of Antibody Tests

When an invader like the SARS-CoV-2 coronavirus enters your body, cells called B lymphocytes create antibodies to protect you, according to Johns Hopkins Medicine. These antibodies stick around to defend against the invader in case it ever comes back.

Vaccines teach your body to mimic this response without you actually getting sick. This is is why you develop antibodies after natural infection with a virus and after getting a vaccine.

However, not all antibodies are the same, and not all tests look for the same types of antibodies. The type and quality of the test can affect the results you receive.

Binding Antibody Tests

These common antibody tests use purified proteins of SARS-CoV-2 (not a live virus) to detect the presence of binding antibodies that attach to a virus, per the CDC.

Most of these tests detect antibodies to one of two types of protein from the coronavirus:

• Nucleocapsid (N) protein
• Spike (S) protein

If you were to get infected with SARS-CoV-2, your body would make antibodies in response to multiple viral proteins, including nucleocapsid and spike protein.

On the other hand, the vaccines currently authorized for use in the United States only trigger antibodies against spike protein, so an antibody test after you get the vaccine should only detect antibodies to that spike protein, not to the nucleocapsid protein.

“You want to make sure you’re getting tested for antibodies to the spike protein, because that’s what you would expect to get after the vaccine,” says Dr. Adalja. “If you had a COVID-19 infection, either of the tests would be positive because you’ve been infected with the whole virus.”

Some tests look for antibodies to both the spike protein and the nucleocapsid protein to distinguish between vaccination and infection.

Certain tests look for specific antibodies to these proteins, depending on how long it’s been since you were infected or vaccinated. For instance, you may have heard of IgG antibody tests and IgM antibody tests for COVID-19.

IgG (immunoglobulin G) antibodies are found in all body fluids and are the most common, making up 75 to 80 percent of the antibodies in your body, per Michigan Medicine. They’re very important in fighting viral infections.

IgM (immunoglobulin M) antibodies are found in the blood and lymph fluid and are the first type of antibody made as a response to an infection. They prompt other immune system cells to eliminate foreign substances. IgM antibodies make up about 5 to 10 percent of all antibodies in your body.

“IgG tend to be longer-lived and are typically the antibodies that are tested for in the clinical and research setting to look at long-term protection or immunity,” says Sydney Ramirez, MD, PhD, an infectious disease doctor and researcher at the University of California San Diego and La Jolla Institute for Immunology. “IgM is more often seen early in infection or early after vaccination.”

Neutralizing Antibody Tests

Although binding antibodies attach to a germ, they’re not necessarily guaranteed to do so in a way that prevents it from infecting a cell, per the FDA. Neutralizing antibodies, on other hand, bind to a virus and neutralize the virus to prevent it from infecting a cell.

In that way, neutralizing antibody tests determine the ability of your antibodies to actually prevent infection. They are also quantitative in that they show how many neutralizing antibodies are present.

These tests are typically done with blood samples in a research laboratory, though they can be done in clinical settings too. Although there are different types of these antibody tests, researchers traditionally inject a blood sample with viral particles (which may be made from other virus backbones but with the SARS-CoV-2 spike protein expressed on their surfaces). Researchers can then determine how well the antibodies block the virus from infecting the cells.

Many research studies (including the clinical trials for the COVID-19 vaccine), have used these tests to look specifically at neutralizing antibodies, since these antibodies can block (neutralize) virus particles — preventing them from binding to and infecting your cells.

“These neutralizing antibodies are typically of more interest when studying vaccine-induced immune responses and determining vaccine-induced protection,” says Dr. Ramirez.

The way that neutralization is measured also varies, and some tests are much more sensitive than others. Because of that, it can be challenging to compare neutralizing antibody tests between studies and labs.

Neutralizing antibodies are typically IgG antibody tests but can also be IgA (immunoglobulin A) antibody tests. About 10 to 15 percent of your antibodies are IgA antibodies, but some people don’t make them. IgA antibodies are found in body parts like your nose, breathing passages, and digestive tract, per Michigan Medicine.

 “Most clinical tests do not look for IgA, but IgA can be neutralizing,” says Dr. Ramirez. “IgA is more associated with mucosa and mucosal immunity, which could be important for immunity or infection prevention in the lungs or other parts of the airway in the case of SARS-CoV-2 and other respiratory viruses.”

Experts are still studying the effect of neutralizing antibodies for SARS-CoV-2 in humans. That means your doctor will not be able to tell you what your results mean in terms of your COVID-19 risk, since it’s not yet known what level of neutralizing antibodies would be needed to prevent infection in your body.

Qualitative vs. Quantitative Tests

Some clinical antibody tests are qualitative, which means they’ll simply give you a “positive” or “negative” readout for antibodies rather than an actual level. Others are quantitative, which means they provide an actual antibody level, or titer.

Because we don’t yet know what level of antibodies are correlated with COVID-19 protection, neither a “positive” qualitative or “high” quantitative test can tell you for sure if you’re adequately protected or not.

If you have a “negative” antibody result, you would need to speak to your doctor to determine next steps on an individual basis.

“It would require a physician who understands the antibody testing well enough and also knows the individual’s personal medical history, including medication and vaccination timing and history, so that they could have an informed discussion with the person and make an individual management decision,” says Dr. Ramirez.

That said, we’ll discuss what an antibody test can and can’t tell you about your immunity shortly.

The Quality of Tests Varies

Not all antibody tests are equal, and it’s difficult to know which antibody test you’re getting. If you’re interested in getting an antibody test, ask your doctor for recommendations.

“Most hospital labs [or companies such as] Quest Diagnostics or LabCorp will be using a highly validated antibody test, but some of the other ones you can get are not going to have the same level of quality,” says Dr. Adalja.

You should wait at least two weeks after a one-dose vaccine or two weeks after the final shot of a two-dose vaccine to get an antibody test so your body has the chance to produce detectable antibodies. Getting tested before your body has built up its immune response may result in a test that shows no or low antibodies.

You Can’t Draw Conclusions from Antibody Results

First of all, no guide currently exists to translate the results of an antibody test for what it means for your protection from COVID-19.

“At this point, we don’t know how antibody presence or levels correlate with immunity well enough to say,” says Dr. Ramirez. “For some vaccines that have been in use for a much longer period of time, we have a better idea of which antibody levels correlate with protection.”

For example, health care and lab workers who handle blood samples often have their hepatitis B antibody levels checked to show that they are immune to hepatitis B. For hepatitis B, experts know what level of a specific antibody to the virus is considered protective. If people don’t have high enough levels, they can receive booster vaccines for hepatitis B — or even the entire vaccine series.

There’s also a difference between having no antibodies and having some antibodies.

“It is possible to receive vaccines and not develop antibodies,” says Dr. Ramirez. “This can be a failure of the individual’s immune system to respond to the vaccine and to generate antibody responses.”

In some cases, an individual may have a specific immune system problem that does not allow them to respond to vaccines. That could be due to a problem with their B cells or with helper T cells, which help B cells make antibodies.

However, experts say it would be rare to have no antibodies after receiving the vaccine.

“That’s probably going to be a minority of patients, even immunosuppressed patients,” says Dr. Curtis. “We don’t know, because there aren’t great population-based studies in rheumatic disease populations, but that will probably be an uncommon occurrence.”

What will be more common than receiving zero antibodies on your test: Your antibody level will be a certain number, whether low or high, but you won’t know if that’s a level that means you’re actually protected. “Nobody knows that for healthy people, and nobody knows that for immunocompromised people,” adds Dr. Curtis.

There isn’t enough data on immunocompromised populations yet to determine how they may react to the vaccine, but experts still believe you’ll get some immunity — which is far better than none — if you are immunocompromised.

Even if you’re taking a drug that affects immune system function — like methotrexate, rituximab, or mycophenolate — and an antibody test shows a low level of antibodies, it’s not possible to know exactly what that means yet.

“Given the difficulties with interpreting antibody tests, and that we do not yet know if a specific antibody level post-vaccination can predict protection, it would be difficult to make definitive conclusions,” says Dr. Ramirez.

In the future, doctors may be able to recommend additional booster shots for people who did not have as robust an antibody response — but due to the limited vaccine supply, that’s not possible right now.

“There is no clear guidance for physicians at this time regarding who to give additional doses of vaccine to or when to give them,” says Dr. Ramirez. “There is also not much guidance on how to prioritize additional doses of vaccine for this kind of scenario, while the United States and much of the world is still in the process of administering first and second doses of vaccine to individuals who have not yet been fully immunized.”

Keep in mind that it’s also possible to have some antibodies, but too few for a lab test to detect — which could be an issue with the test or a biological issue.

“In the case of someone making antibody levels that are too low to detect, it is possible that the antibody levels would rise to a detectable level over time — say, if the test was performed too soon — or that the antibody levels would rise to a detectable level following a booster dose of the vaccine,” says Dr. Ramirez.

Protection Against COVID-19 Is About More Than Just Antibodies

Importantly, the COVID-19 vaccine may confer protection that goes beyond antibodies.

“There’s not just one arm of the immune system,” says Dr. Adalja. “In addition to the antibodies that are generated after vaccination, people also generate T cell immunity, which may be equally important, but harder to measure and not reflected in an antibody test.”

It’s thought that vaccination also causes a T cell response in your body. Your immune system’s T cells might not be able to prevent SARS-CoV-2 infection unless there is a low level of virus, but they are likely important for clearing the SARS-CoV-2 virus from the body once infection has occurred.

“We’ve seen that hospitalized individuals with COVID-19 had less severe disease and better clinical outcomes if they had T cells that could recognize the SARS-CoV-2 virus,” says Dr. Ramirez. “T cells should help limit the severity and duration of infection if it occurs. T cells also help improve the antibody responses that are made to the SARS-CoV-2 virus.”

The Bottom Line

 There are currently too many unknowns to get an antibody test after a COVID-19 vaccine and expect any tangible takeaways, even or especially if you’re immunocompromised.

“We’re really only in the infancy of understanding how well this vaccine works in the immunosuppressed population, but that will be an area a lot of people are going to be generating data from,” says Dr. Adalja.

The best thing you can do right now: Get the COVID-19 vaccine and continue to follow standard mitigation measures to avoid exposure to the virus. Here’s more information on preventive steps to take after getting the vaccine if you’re immunocompromised.

And if you have gotten an antibody test after your COVID-19 vaccine and are concerned about the results, keep in mind that it may not be showing the full story.

“I wouldn’t panic — just realize the antibody test is not the only way to measure your immune system response, and we’ll have more information on how people who are immunosuppressed fare with this vaccine in terms of what protection level they get,” says Dr. Adalja.

That data may help inform guidance for boosters based on your immunosuppressive status or help to determine certain vaccines that might be better for the immunosuppressed in the future.

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