Scientists and doctors across Massachusetts are mobilizing to address two of the most baffling questions of this pandemic: How widely has the coronavirus spread — and if you’ve been infected, do you have lasting immunity?
The answers lie in the antibody test — a pinprick of blood that captures the body’s immune response. Researchers say such testing is the foundation upon which policymakers can determine when the Commonwealth can safely, fully reopen.
As pilot antibody testing projects launch across the country, Massachusetts is seeing a surge of energy in the front lines of the field — and key results could be just a few months away. One project at the Broad Institute of MIT and Harvard is ramping up to run thousands of antibody tests per day. Other local researchers are examining long-term immunity by testing people’s antibody responses after infection and following them over time to see if they get reinfected.
“I think this is if not the center of the universe for this, it’s close to the center of the universe,” said David R. Walt, a professor of biologically inspired engineering at Harvard Medical School. “But it requires more than innovation and brainpower. It requires the ability to engage with the commercial sector to be able to scale these things. That, too, I think is a big advantage of Massachusetts, in that we’ve got a bunch of life science companies in Cambridge and Boston that really can help bring some of this to the next phase.”
Much attention has been focused on the urgent need for more coronavirus tests. But viral tests, which typically use a nasal or throat swab to capture a sample, produce results only when the virus is active in the body.
Antibody testing, also known as serology testing, can reveal if someone was infected in the past, even if they recovered or never felt significant symptoms. That’s because antibodies may linger for months or years. So serology testing is vital for both measuring the pandemic’s reach and potentially providing information about immunity.
“The importance of antibody testing can’t be stressed enough,” said Dr. Bruce Walker, director of the Ragon Institute of MGH, MIT, and Harvard, during a recent symposium on advances in antibody research hosted by the Massachusetts Consortium on Pathogen Readiness.
Dr. Michael Mina, an assistant professor of epidemiology at Harvard’s T. H. Chan School of Public Health, is among those advising Governor Charlie Baker on the crisis. But it’s hard to make concrete plans, Mina said, without knowing how pervasive the coronavirus is.
For example, Mina posed, has it infected 1 percent or 15 percent of residents? Knowing that, he explained, would tell us how deadly it is, how at-risk some populations may be, and how much herd immunity we potentially have.
“Right now, we’re really flying blind," Mina said. ”We still don’t know, are we seeing just the tip of an iceberg? Or are we seeing a third of the iceberg?”
So Mina and colleagues are launching serological surveys to provide crucial missing data. “There’s a tremendous number of studies that are getting developed right now” in Boston’s research and biomedical community, Mina said. Some studies will test health care workers and patients, some will follow people in their homes, and others will use blood banks and blood donors to get quick access to a large subset of the population, he said.
State officials are collaborating on serological surveillance efforts, but not providing funding, said a Department of Public Health spokesperson.
Serology testing “is very important for understanding the epidemiology of COVID,” said Dr. Larry Madoff, medical director of the Bureau of Infectious Disease and Laboratory Sciences at the DPH, in a statement. “We are working with researchers to look at population immunity to COVID and expect to be involved in a number of studies.”
Mina’s team has been conducting a serological survey in Cambridge, and he is planning large-scale antibody studies throughout Massachusetts.
Dr. John Iafrate, vice chairman of Massachusetts General Hospital’s pathology department, led an eye-opening antibody study that found nearly a third of Chelsea residents in a recent sample tested positive. MGH is also doing testing for a Boston serological survey of 1,000 residents.
At the University of Massachusetts Amherst, Andrew Lover, an assistant professor of epidemiology, is preparing a serological study of UMass students, faculty, staff, and others from participants’ households.
Further antibody surveys by doctors at MGH, Brigham and Women’s Hospital, and Beth Israel Deaconess Medical Center are underway or awaiting approval. Some researchers will follow subjects over time, which could be invaluable in determining whether people who have recovered from the virus can get it again — or spread it to others.
To be sure, there are caveats regarding antibody testing. Multiple coronavirus antibody tests have flooded the market without formal Food and Drug Administration review, and a recent analysis of 12 tests found that most were not consistently reliable. “People shouldn’t consider them as anything more than a toy,” Mina said of direct-to-consumer antibody tests during a recent press briefing.
In addition, much is still unknown about the connection between coronavirus antibodies and immunity. “Many experts believe that infection with COVID will confer protective immunity to re-infection, but this has not yet been reliably demonstrated,” said Madoff. “Even if true, the extent and duration of immunity remain uncertain.”
“The last thing we want is this conception that having antibodies is actually a passport to reenter society, because it is not,” said Galit Alter, a professor at the Ragon Institute. The World Health Organization has warned that without more information, issuing “immunity passports” could “increase the risks of continued transmission.”
Baker echoed those doubts at a recent press briefing, suggesting that until the FDA vets and approves antibody tests, widespread serology testing would not be a state priority.
“Broad antibody testing needs the federal government, and especially the FDA, to step up and get states and providers a lot more guidance than we have now, so that we can get to a point where we’re using a test that doesn’t have false readings,” the governor said.
Still, local scientists and doctors are pushing forward. The Broad Institute is involved in a number of research collaborations involving universities, hospitals, government, and industry to evaluate and use new types of tests, including antibody tests, a spokesman said.
Alter and colleagues at the Ragon Institute and MGH built a highly accurate antibody test and brought it to the Broad Institute, where automation will ramp up production. They’re running more than 1,000 tests a day for research purposes, and Alter hopes to hit 10,000 per day in a couple of weeks.
Many direct-to-consumer antibody tests look like pregnancy tests, offering a simple positive or negative result. But the Broad is running a more sophisticated test that shows the levels of three antibodies, Alter says, with 99 percent accuracy 14 days after the onset of symptoms.
“What we're hoping is that there's going to be an actual numerical number that will give us a cutoff of protection,” Alter said.
Combining those results with data from sero-epidemiology studies that track people over time, checking for any reinfection, Alter seeks to understand what level and quality of antibodies will confer immunity protection.
“The minute we have that information, then we can reenter society. Because that is all the knowledge we need,” said Alter, who estimated that such results could be three to six months away. “It’s not that long to wait and be able to — with actual data — say definitively if you go out there, you are going to be safe.”
Experts agree that antibody testing will ultimately need to be done on a mass scale to meet the needs of the marketplace. “Probably every Uber driver’s going to want to know if they’re infected, every restaurant’s going to want to have their people tested,” said Alter.
So even as policymakers seek federal guidance and FDA-approved antibody tests, researchers are exploring ways to make high-quality tests more widely available, including commercial collaborations.
“The problem is that there’s just no time; we can’t wait,” Alter said. “We need to build something now. Because if we wait for those guys to put out their perfect, FDA-approved tests, then we basically just watch the epidemic spread through the population, and we have no information.”
Walt, who co-directs the Mass General Brigham Center for COVID Innovation, forecasts that when Massachusetts residents return to their workplaces, many could need repeated antibody tests, adding up to perhaps half a million tests per week.
So his team examined scores of consumer and “point-of-care” tests — the kind that could be used in doctors’ offices — and is vetting the best ones. Walt plans to publish the final results, and once the top performers are clinically validated, employ them in communities and hospitals under clinical supervision.
Last month the federal government began requiring health insurers to cover antibody tests for free. But Mina is calling for public support of serological studies, noting that unlike diagnostic COVID-19 testing in health care settings, serological surveillance has no clear path for reimbursement. He hopes the state will provide funding, he said.
“I am very concerned that these efforts may fall flat if there is not a rapid infusion of monetary and political support to ensure they get off the ground in a way that is useful for public health," Mina said.