Marisa Peryer

As thousands of Americans become infected with COVID-19 each day, and many more begin their recovery, medical experts are looking to antibody tests — intended to show whether people have built immunity to the virus — as the key to reopening the country.

Researchers at Yale New Haven Hospital and the Yale School of Medicine are mounting an effort — spearheaded by department chair and professor of epidemiology and medicine Albert Ko — to investigate the many unanswered questions surrounding SARS-CoV-2 antibodies.  Much of the work is theoretical, and the investigation is likely to remain ongoing for months. But researchers say that the answers that this work might unearth have the potential to be game-changing, with implications for the development of vaccines and other treatments.

“The basic biology here is extraordinarily interesting, but it’s also very frustrating because people want to know if they’re protected or not and scientists have to learn to live with uncertainty,” said Aaron Ring, an assistant professor of immunobiology whose lab is studying SARS-CoV-2 antibodies. “This is a novel virus. We’ve only been studying it for just a few months, and there are so many questions that we’re not going to be able to address immediately.”

Ring’s lab is running a research study surrounding SARS-CoV-2 antibodies isolated from healthcare workers at YNHH. He said his lab’s goal is not to develop a clinical-grade antibody test to be used in hospitals, but rather to fully understand what it means to have these antibodies.

The first question that could be answered by this research is determining what the true prevalence of the virus is among healthcare workers, Ring explained.

“This work allows us to understand to what extent the virus has spread and how the disease spreads, especially among healthcare workers,” Feimei Liu GRD ’23, a bioengineering graduate student, wrote in an email.

She explained they are using a test that can measure the antibody levels in a person’s blood, which could indicate whether or not they have already been exposed to the virus. Because so many people do not have symptoms when they are infected with SARS-CoV-2, antibody tests could potentially show who has actually been infected, in contrast to the number of infections coming from current testing.

According to Ring, understanding the true scope of the virus’ spread can also reveal the effectiveness of the protective measures that have been implemented since March. Because healthcare workers are on the frontlines of the pandemic — and are at greatest risk of exposure — they are a good litmus test for the effectiveness of current measures.

“If many of them were getting infected, then we would be really concerned that we weren’t taking enough precautions with the PPE and other procedures,” Ring said. “Whereas if we don’t see any infections, that would give us confidence that at least some of the efforts we were taking were effective in reducing the risk of the healthcare workers getting infected.”

Researchers like Ring and Ko are also trying to determine how significant it is to possess SARS-CoV-2 antibodies. Liu emphasized that having antibodies might not necessarily mean that a person is immune, and in some cases, possessing the antibodies could pose risks.

As medical professionals speculate about the power of antibodies, many have raised the idea of an “immunity passport,” which would confer resistance from reinfection and would allow for people to reenter life as normal. Ring said that “there’s no evidence to support that that’s ever going to happen,” emphasizing that it is difficult to be prescriptive without a fuller understanding of the antibodies.

“It has been shown that antibodies are a two-edged sword,” Ring said. “On the one hand, they can neutralize the virus, and they can prevent it from infecting other cells, but on the other hand … you can get situations where you don’t fully block a virus and you hyperactivate the immune system.”

Scientists do not know how cells respond to SARS-CoV-2 antibodies. To complicate matters slightly, earlier this week, reports out of South Korea indicated that people who had previously tested positive for the virus are now showing signs of reinfection.

“We don’t know the durability of the immunity,” Ring said. He added that even the people with the earliest cases of COVID-19 are only a few months past their infection, so it is hard to know if immunity could last beyond that time span, if at all.

“Having an antibody that can bind to the viral protein in the lab is a long way from having a cure,” Liu said. “A fundamental understanding of the protective antibody response is crucial for guiding vaccine design and development of new therapeutics that are safe and effective.”

Ko, who was unable to provide comment on his research, was appointed by Connecticut Gov. Ned Lamont last week to serve on an advisory board for reopening the state of Connecticut. His lab has been working on research similar to Ring’s, which may have implications for future treatments.

“We’re constantly learning,” Ko said during a press conference with Lamont on Thursday. “We’re going to have new diagnostics, new therapeutics and hopefully new vaccines.”

Understanding the harms and benefits of SARS-CoV-2 antibodies will be critical in developing safe treatments. According to Ring, even if the antibodies harm people’s immune systems, treatments can be tailored to target these dangerous responses.

“A vaccine is going to be the ultimate way of extinguishing this pandemic,” Ring said. “But we need to really understand if there are good and if there are bad antibody responses because if there are harmful antibody responses, we want to make sure that vaccines do not elicit them.”

Ring said that the process for researching these questions about vaccines will be tedious, but for good cause — “this vaccine, when it comes out, could be given to billions of people. I think it’s really important to dot the i’s, cross the t’s and really gain as much assurance as we can,” he said.

In discussing the theoretical social implications of this research, Ring cited the movie Contagion. In the film, people who are known to be protected against reinfection are given immunity bracelets to show that they are fully protected now. This may not be the case with COVID-19.

“What we don’t want to do — and I think this is the most important part — is give people license to think that they can stop taking precautions,” Ring said. “I think that would be the biggest mistake that people could draw from an antibody test with the level of data we have now.”

As of Monday evening, there have been 19,815 laboratory-confirmed cases of COVID-19 in Connecticut.

Charlotte Zimmer | charlotte.zimmer@yale.edu