Leave Your Antibodies Alone

a row of six antibody tests showing different results
The Atlantic

Antibody tests for the coronavirus have just one scientifically sanctioned job in the clinic. Designed to detect a delayed immune response to the virus, they can help patients determine whether they were once infected—effectively, a retroactive diagnosis.

That’s not how a lot of antibody tests are being used.

Across the country, people have flocked to test sites to determine whether they are “immune” to the coronavirus, or even to obtain results that could green-light them to board an international flight. Now they are taking these tests to check whether the vaccine they received actually took. Some experts are even debating whether the tests could serve as a screening tool to identify candidates who might be eligible to skip their second COVID-19 shot.

“I think there’s still a lot of confusion,” Elitza Theel, an expert in antibody testing at the Mayo Clinic in Rochester, Minnesota, told me.

The temptation is clear: Amid a pandemic that’s infected more than 106 million people, leaving more than 2 million dead, people are eager to learn if they’ve built up immunity to the coronavirus—a possibility that could, like a passport, clear them to move about freely despite the virus’s rampant spread. But antibody tests can’t provide the definitive answers we seek. They are memoirists, not prognosticators: The results they yield give us a glimpse of the pathogens we’ve encountered in the past, rather than a forecast of the infections we’ll experience in the future.

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Antibodies start to appear in the blood at detectable levels about a week or two after an infection begins. They’re made by immune cells called B cells and can carry out a bevy of virus-fighting functions. Some are team players: They glom on to pathogens and flag them for destruction by other immune molecules or cells. Some are lone assassins: They latch on to viruses so tightly that they render them incapable of entering human cells.

As the immune system purges a virus, B cells that recognize it will stand down, and antibody levels will decline. But a few lingering B cells will continue to eke out a small number of antibodies for weeks, months, even years after the initial threat has passed, leaving traces in the blood that sensitive antibody tests can easily pick up.

Since the appearance of antibodies lags behind that of the virus, diagnostics experts don’t use antibody tests to check for active coronavirus infections. Antibody tests hunt for reactions to the pathogen, not the pathogen itself—akin to surveying coffee-shop patrons for alertness and jitters, instead of just checking their drinks for caffeine. The tests won’t turn positive when the coronavirus first infiltrates the body. But they will stay positive long after it has left. For patients who have been sick for many days or even weeks, but receive only negative results on standard PCR tests, an antibody test may be a sort of last diagnostic resort. Beyond that, “I can’t think of a reason I would want to use an antibody test,” says Esther Babady, the director of the clinical microbiology laboratory at the Memorial Sloan Kettering Cancer Center.

And yet these tests continue to be cast in the wrong roles. Some countries, such as Peru, turned to the tests in a last-ditch attempt to fill their diagnostic gaps, with disastrous results. In November, China began requiring inbound air travelers to present negative antibody tests to enter the country—even though such results can neither rule out infection nor guarantee that someone is not contagious.

Experts have repeatedly debunked the idea that the tests can prove that a person is immune to the virus. But the tantalizing possibility has made that reputation stick. Months after many tests were pulled off the market for false advertising or shoddy performance, companies continued to tout them as passports that could clear people to return to work, school, or travel. Theel suspects that some individuals who are eager to know their immune status may still be serially testing themselves. A handful of patients at the Mayo Clinic, she said, have sought out nearly a dozen tests in the past five or six months.

Postvaccination antibody tests might hold a similar allure. Last month, a distressed friend texted me after her father tested negative for antibodies—a surprise, considering he had recently received his second dose of Moderna’s COVID-19 vaccine. But it turned out that her father had taken the wrong type of test—one designed to look for antibodies that recognize a protein called nucleocapsid, which is found in the coronavirus but not in the Moderna vaccine. (Moderna’s shots instead trigger the production of antibodies against another coronavirus protein, called spike; I’d bet that my friend’s father is chock-full of these antibodies.)

Theel said she sympathizes with the temptation to do the occasional antibody check, whether after a suspected infection or a vaccine. When she posted an informal poll to Twitter last month, more than 80 percent of the 118 people who responded said they’d be interested in testing themselves for antibodies after their jabs. “I think it’s a psychological thing,” Theel said. “You injected something in my body. I want to know: Did I respond?

Antibodies do make up a crucial component of the immune system, especially when it comes to warding off viral disease. But positive tests for coronavirus antibodies have no bearing on whether these molecules will actually quash the virus in a more natural setting, or on how long their protective powers will last. And researchers don’t yet know what antibody levels are needed to ward off infection or disease. “It’s hard to use antibodies as a thing saying, ‘I’m protected from future disease,’” Nahid Bhadelia, an infectious-disease physician and the medical director of the special-pathogens unit at Boston Medical Center, told me. The portrait of protection has grown only more complex as the coronavirus has continued to splinter into variants, some of which appear to evade the pathogen-purging powers of certain antibodies.

For people who are still keen on testing themselves postvaccination, Theel and Babady both recommend waiting until about a week or two after the second shot and seeking out a test that detects a type of antibody called immunoglobulin G, or IgG, that will recognize the coronavirus’s spike protein. And a negative result shouldn’t necessarily cause alarm. Some tests are better than others at picking up low levels of antibodies. Not everyone will make enough antibodies to trip a typical test, but they could still be well protected against the virus, thanks to the many other immune molecules and cells our bodies produce.

Antibody tests do have a role to play in research. Public-health experts routinely use them to track where the coronavirus has silently spread. Measured in a lab, neutralizing antibodies can also aid the development of vaccines or treatments such as convalescent plasma and monoclonal antibodies. And as new variants of the coronavirus continue to spring up around the globe, antibody studies will help scientists suss out how well antibodies generated in response to one version of the virus will work against another.

Last week, two preprint studies seemed to hint at yet another use for antibody tests: a prevaccination screening strategy for people who have already been infected by the coronavirus. With antibodies that recognize the virus already teeming in their blood, these people might not need their second dose of the Pfizer-BioNTech or Moderna vaccines, some researchers argue. “Scientifically, it might make sense,” Theel said. “You’re basically boosting the immune system with the first dose, after a previous infection.” But with so much ambiguity about how many antibodies are needed for protection, Theel is still cautious about endorsing the idea. Doling out two shots to everyone, regardless of antibody status, remains the safest bet, since the second injection doesn’t seem to pose any threat to COVID-19 survivors.

A year into the pandemic, the consensus on antibody tests is largely the same as it was months ago: A positive result “shouldn’t change anyone’s behavior,” Bhadelia said. The unknowns about immunity have shrunk. But they’re still too big to gamble with.