Antibody tests can’t give answers you want about COVID-19 immunity
Talk of the need for coronavirus booster shots has prompted many Americans to seek antibody tests.
In most cases, however, getting an antibody test to determine immunity is a fool's errand, infectious-disease doctors agree. The tests for antibodies, also known as serology tests, do not provide the answers that most people are seeking.
Both the Centers for Disease Control and Prevention and the Food and Drug Administration advise against using antibody tests to determine one's level of immunity against COVID-19, the disease caused by the coronavirus. So does the Infectious Disease Society of America, which represents infectious-disease specialists.
While some states, including Maryland and South Carolina, are conducting targeted antibody testing for specific purposes, no state is promoting the tests' use for residents to determine whether they have sufficient immunity or need a booster shot.
The tests might indicate the presence or even the level of coronavirus-fighting antibodies in the bloodstream, but scientists don't yet know what number of antibodies provide protection from COVID-19. Antibodies are protein molecules the immune system produces to neutralize viruses or bacteria that have entered the body.
Antibody levels do help health-care providers establish whether a patient has immunity against other, more familiar infectious diseases, such as measles and hepatitis A and B. But doctors say our relatively short experience with COVID-19 hasn't yet provided the same information.
"Because our journey is so young, we don't yet know what value means immunity," said Mary Hopkins, associate program director of the Infectious Disease Fellowship Program at Tufts Medical Center.
Testing for coronavirus antibodies has some benefits — especially for determining whether someone with COVID-like symptoms had an earlier, undetected COVID-19 infection — but not for the reasons many are seeking the tests.
"Doctors are ordering antibody tests for people who are worried about waning immunity, but I see that as problematic," said Alan Wells, medical director of clinical labs at the University of Pittsburgh Medical Center. "For a normal person, knowing your level eight months later (after their initial vaccine dosages) is of relatively little value."
In general, the more antibodies, the better, Wells said. But even with a low level of antibodies months after exposure or receiving a vaccine, the body can mount a stout defense against the virus by generating new antibodies in response to a fresh infection. "There is more to your immune response than antibody levels," Wells said.
Wells said his hospital, like others, has had a big increase in requests for antibody tests in recent weeks, although he recommends to his colleagues that they use them judiciously.
Another problem with coronavirus antibody tests, doctors say, is that they are not standardized, so values associated with antibody tests in one version might not be the same as another.
Some states perform antibody testing on a targeted basis. In South Carolina, the Department of Health and Environmental Control conducts sample antibody testing for vaccinated people to correlate antibody levels with episodes of reinfections or breakthrough cases, said Derrek Asberry, a spokesperson for the department.
Maryland has done antibody testing on more than 500 nursing home residents and determined that 50% of them showed declining antibodies over time. On the basis of those tests, Gov. Larry Hogan ordered boosters for all older Marylanders living in congregate housing.
Hopkins said large-scale antibody testing eventually should help to determine what antibody levels would provide coronavirus immunity.
"It would be wonderful and important if you could test every month 5,000 patients 60 years and older and find out who gets reinfections or infections for the first time and see if there is a correlation," she said. "If you found infections and could say those people had antibodies below 200, that would be helpful."
Some antibody tests are able to assign a numerical value to an individual's antibody levels, although the numbers are not uniform from one manufacturer's test to another. The level above which a person can be considered to have sufficient immunity is unknown.
In Kentucky, the state Senate passed a resolution in September that would have enabled residents to substitute an antibody test for proof of vaccination. The resolution proposed that an individual with antibodies at a level above the 20th percentile of the immunized population should be recognized as having protection equal to that of a fully immunized individual. The measure died when the state House didn't take it up before the special session ended in September.
Doctors interviewed for this story said that without knowing what level of antibodies provides immunity or the parameters — especially the timing — of testing vaccinated people, such a measure may not provide the assurance its sponsors suggested. But Wells added that the idea is not without merit, because higher levels of antibodies do correlate with fewer hospitalizations and deaths.
Thomas Denny, chief operating officer at Duke University School of Medicine's Human Vaccine Institute, however, said the resolution's demise was probably a positive development.
"Given how few labs can do this test and the issues of test validation, it's good that this bill died," he wrote in an email. "Also, I would need to go review data in the literature but not sure their stated criteria makes sense."
Antibody testing can determine whether someone has been exposed to coronavirus or has received any of the vaccines used against the virus. Some tests detect antibodies created in either case. Others only detect antibodies that are generated by exposure.
Those tests are different from the PCR (polymerase chain reaction) tests most often used to determine whether someone has the virus. A PCR test detects genetic material present in the coronavirus.
From early in the pandemic, public health agencies and other medical organizations used PCR tests or antigen tests, which detect certain proteins in the virus and are cheaper and faster though less reliable than PCR tests, as the main tool for diagnosing people with the virus.
Health-care workers didn't generally use antibody tests because, as Elitza Theel, an expert in serologic testing at the Mayo Clinic, an academic research center, said, "It takes a good one or two weeks after infection to get a detectable level of antibodies.
"You don't want to rely on an antibody test because you will miss people who are acutely affected."
Hopkins said that antibody tests are useful for patients suspected of having long COVID-19, the lingering severe symptoms that affect some people months after their first exposure to the virus. PCR tests only detect the virus in its initial phase, in the first two weeks or so.
If someone with COVID-19 doesn't get a PCR test in that time, the best way to determine exposure later is with an antibody test, even months after contact with the virus, Hopkins said. "When I see a patient in my clinic who's short of breath or has mysterious aches, I give them an antibody test to see if it's long COVID."
Doctors say antibody testing also can be useful in determining whether individuals, especially nursing home residents, developed antibodies after they were vaccinated. If not, they could be considered good candidates for infusion with monoclonal antibodies to mimic antibodies produced by the immune system.
Antibody testing also benefits immunocompromised patients, such as those undergoing cancer treatment, Denny said. "We can test those individuals and show their levels are much lower than the general population and give them a boost and test them again and see if their numbers go up," he said.
Still, doctors say, healthy people should be reassured that the human immune system remembers what to do in the face of a new risk.
Even as the initial antibodies decline after a coronavirus infection or vaccine, the memory cells store information about the original attack, react to a renewed threat and begin to stimulate the body to resume its defense, including by generating a whole new army of antibodies.
People "shouldn't freak out" if they learn their coronavirus antibodies have declined over time, Theel said.
"Memory immunity remains strong. That's what we need to underscore to the public."
This report is a product of Stateline, an initiative of the Pew Charitable Trusts.