Antibody test type and timing key in gauging COVID immunity
By Apoorva Mandavilli
Now that tens of millions of Americans are vaccinated against the coronavirus, many are wondering: Do I have enough antibodies to keep me safe?
For a vast majority of people, the answer is yes. That has not stopped hordes from stampeding to the local doc-in-a-box for antibody testing. But to get a reliable answer from testing, vaccinated people have to get a specific kind of test, and at the right time.
Take the test too soon or rely on one that looks for the wrong antibodies — all too easy to do, given the befuddling array of tests now available — and you may believe yourself to still be vulnerable when you are not.
Actually, scientists would prefer that the average vaccinated person not get antibody testing at all, on the grounds that it is unnecessary. In clinical trials, the vaccines authorized in the United States provoked a strong antibody response in virtually all of the participants.
“Most people shouldn’t even be worrying about this,” said Akiko Iwasaki, an immunologist at Yale University.
But antibody tests can be crucial for people with weak immune systems or those who take certain medications — a broad category encompassing millions of people who are recipients of organ donations, have certain blood cancers or take steroids or other drugs that suppress the immune system. Mounting evidence suggests that a significant proportion of these people do not produce a sufficient antibody response after vaccination.
If you must get tested or just want to, it is essential to get the right kind of test.
“I feel a little bit hesitant to recommend everybody getting tested, because unless they really understood what the test is doing, people might get this wrong sense of not having developed any antibodies,” Iwasaki said.
Early in the pandemic, many commercial tests were designed to look for antibodies to a coronavirus protein called the nucleocapsid, or just N, because after infection, those antibodies were plentiful in the blood.
But these antibodies are not as powerful as those required to prevent virus infection, nor do they last as long. More importantly, antibodies to the N protein are not produced by the vaccines authorized in the United States; instead, those vaccines provoke antibodies to another protein sitting on the surface of the virus, called the spike.
If people who were never infected are vaccinated and then are tested for antibodies to the N protein instead of the spike, they may be in for a rude shock.
David Lat, a 46-year-old legal writer in New York City, was hospitalized for COVID-19 for three weeks in March 2020, and he chronicled most of his illness and recovery on Twitter.
Over the next year, Lat was tested for antibodies numerous times — when he went to his pulmonologist or cardiologist for follow-ups, for example, or to donate plasma. His antibody levels were high in June 2020 but steadily fell over the following months.
The decline “didn’t worry me,” Lat recalled recently. “I had been told to expect that they would naturally wane, but I was just happy that I was still positive.”
Lat was fully vaccinated by March 22 of this year. But an antibody test April 21, ordered by his cardiologist, was barely positive. Lat was stunned. “I would have thought a month after being immunized, I would have antibodies through the roof,” he said.
Lat turned to Twitter for an explanation. Florian Krammer, an immunologist at the Icahn School of Medicine at Mount Sinai in New York City, responded, asking Lat which test had been used. “That’s when I looked at the fine print on the test,” Lat said. He realized it was a test for antibodies to the N protein, not to the spike.
“It seems that by default, they just give you the nucleocapsid one,” Lat said. “I never thought to ask for a different one.”
In May, the Food and Drug Administration recommended against the use of antibody tests for assessing immunity — a decision that has drawn criticism from some scientists — and provided only bare-bones information about testing to health care providers. Many doctors are still unaware of the differences between antibody tests or the fact that the tests measure just one form of immunity to the virus.
Rapid tests that are commonly available deliver a yes-no result and may miss low levels of antibodies. A certain type of lab test, called an Elisa test, may offer a semiquantitative estimate of antibodies to the spike protein.
It is also important to wait to be tested at least two weeks after the second shot of the Pfizer-BioNTech or Moderna vaccines, when antibody levels will have risen enough to be detectable. For some people receiving the Johnson & Johnson vaccine, that period may be as long as four weeks.
“It’s the timing and the antigen and the sensitivity of the assay — these are going to be very important,” Iwasaki said.
In November, the World Health Organization set standards for antibody testing, allowing for comparison of different tests. “There’s a lot of good tests out there now,” Krammer said. “Little by little, all these manufacturers, all these places that run them are adapting to international units.”
Antibodies are just one aspect of immunity, noted Dr. Dorry Segev, a transplant surgeon and researcher at Johns Hopkins University. “There’s a lot happening under the surface that antibody tests are not directly measuring,” Segev said. The body also maintains so-called cellular immunity, a complex network of defenders that also responds to invaders.
Still, for someone who is vaccinated but immunocompromised, it may be helpful to know that protection against the virus is not what it should be, he said. For example, a transplant patient with poor antibody levels might be able to use test results to convince an employer that he or she should continue to work remotely.
Lat has not sought another test. Just learning that the vaccine most likely has given him a fresh increase of antibodies, despite his test results, was reassurance enough. “I trust that the vaccines work,” he said.