Blood tests for antibodies to the novel coronavirus will be “foundational, fundamental,” to sending Californians back to work, California Gov. Gavin Newsom said on Monday—but medical experts caution that there’s still a lot we don’t know about whether the tests are reliable enough to ensure people’s safety.
Testing people’s blood for antibodies may help determine who has already had the disease and recovered. But just because someone tests positive for antibodies doesn’t necessarily mean they are immune to the virus—or that they will remain that way over time.
Antibodies are immune proteins that attack viruses and other pathogens. Unlike the diagnostic tests that are backlogged across the country, antibody tests—sometimes called serologic tests—don’t sniff out the virus itself. Instead, they search the blood for these proteins, teasing out who has been infected, and who hasn’t.
“We really need the antibody test. The whole country is waiting for a good antibody test,” said Philip Norris, a professor of laboratory medicine at the University of California, San Francisco, and vice president of research at Vitalant Research Institute. “It will change how we can address this epidemic so dramatically. We’re operating with blinders on now.”
Newsom said that figuring out whether people have antibodies to the virus “will allow us to process new protocols in order to get people back into the workforce, or least back into society in more traditional ways.”
Charity Dean, assistant director at the California Department of Public Health, congratulated Stanford University about its development of an antibody test on Saturday. “We’re very excited that this is a California home-grown test that is going to be rolled out in the next week for actual use on Californians,” Dean said.
Stanford spokeswoman Lisa Kim said that the university has developed two antibody tests—one for use in research, and the other for use in the lab. But she declined to discuss the timeframe or make any experts available for an interview.
Some People Already Are Being Tested
Antibody testing of some people already is occurring. The Centers for Disease Control and Prevention is using the tests to survey hotspots for viral spread. A team at Vitalant is testing blood donors from across the country with multiple antibody screens.
Stanford has rolled out a community-wide antibody surveillance effort, The Mercury News reported. And the Food and Drug Administration recently granted emergency use authorization to one antibody test developed by a company called Cellex.
But even when a reliable test is developed, its production and use has to be scaled up to reach millions of people.
There’s a balance to navigate, said David Pride, associate director of University of California, San Diego’s, clinical microbiology lab—between waiting until scientists fully understand immunity to the novel coronavirus, or allowing people to go out in public again.
“We can know the answers eventually,” he said. “But what are we going to do three months from now? What are we going to tell people—stay at home, or go out? So there’s the strict science, ‘We have to go with the data,’ and then there’s the, ‘What is practical to get life back to normal?’ And those two things are almost in direct opposition.”
Norris expects to see the test prioritized for healthcare workers—for whom every extra bit of protection helps.
“At the medical centers, everybody would love to get an antibody test so that we can apportion those on the front line, and give those jobs to folks who already have antibodies,” he said. “So in theory, I do think it’s a great idea.”
Does Immunity Last?
Relying on antibody tests to determine who can avoid the shelter-in-place order means answering a big question: Can you get the new coronavirus twice?
Right now, reports are mixed. But preliminary findings in monkeys suggest that once infected with the virus, reinfection was unlikely a month later. The evidence hasn’t yet been published in an academic journal, but a team of infectious disease experts called the results reassuring in the Journal of the American Medical Association.
“I think it’s probably a good assumption that if you had (the virus), and you developed an antibody response, you’re unlikely to get it again in the short term,” Pride said.
Researchers around the world are racing to find out for certain—and whether protection persists long-term.
“It won’t be tomorrow,” Norris said. “But people are working hard to make it happen.”
The epidemic started only a few months ago, so there have been no long-term investigations into immunity, according to an article published Monday in the Journal of the American Medical Association. There are also no biological markers yet to separate those who are still vulnerable from those who are immune, such as the levels of antibodies that are protective.
“We don’t know what the correlation is between the antibody levels that we measure and the protection that’s conferred by that antibody,” said Philip Felgner, director of the vaccine research and development center at the UC Irvine School of Medicine. “That’s the link that we don’t have yet.”
Early research suggests that most people infected start producing antibodies against the novel coronavirus between one and two weeks after showing symptoms. And preliminary studies hint that these antibodies can neutralize the virus. Μore research is needed to bear that out.
To test whether antibodies can block the virus from penetrating cells, Norris’ colleague at Vitalant created a safer stand-in for the virus by equipping the more benign vesicular stomatitis virus with a key coronavirus protein. Then he mixed his declawed virus with cells, and added serum from two patients who had recovered.
The antibodies blocked the virus from getting inside the cells, preventing a successful infection. That’s the rationale behind treating sick patients with plasma filled with antibodies from people who have recovered. However, clinical trials are needed to determine if it works.
There’s another open question: How long does immunity last?Long-term follow-ups of people who survived the first SARS epidemic in 2002 and 2003 suggest that their antibodies lasted for about two years, before disappearing in about a quarter of the study participants after three years.
Studies of milder coronaviruses indicate that reinfection is possible, but that the symptoms tend to be less severe the second time around.
In the 1990s, a team of scientists in the United Kingdom spritzed “nasal washings” containing a mild coronavirus up the noses of 15 volunteers. Ten became infected; eight came down with colds; and a year later, most of the infected volunteers had slightly higher levels f antibodies in their blood than the volunteers who weren’t infected.
When the volunteers were re-exposed a year later, all five who hadn’t been infected the first time became infected, and one showed symptoms. Of the ones who had been infected the previous year, two-thirds became re-infected—but none developed symptoms.
Again, it’s hard to draw conclusions from such a small study. But that, and the possibility that the virus itself might change over time, is why Felgner cautions against pinning hopes on the idea that antibodies mean imperviousness to the virus. Instead, he proposed a more measured view:
“They’re going to have to say this immune response that’s being measured here doesn’t necessarily protect me entirely from this infection. But it may reduce the severity if I do get another exposure,” he said.
The Worst-Case Scenario: False Security
It’s one thing to use an antibody test academically to investigate the virus—where it spreads and how people’s bodies fight it off. It’s another thing to rely on it to shape public policy and determine who should take on greater risks of exposure—which is what Newsom has hinted at.
Newsom said last week that testing for antibodies “is all part of our strategy to get people … back into some semblance of normalcy.”
But it’s still too early for Felgner to be completely comfortable with that idea. Antibody responses vary from person to person. Some may not make enough or send the right kinds to the lungs to fight off the virus.
“That’s what gives everybody who works on the science a queasy feeling of insecurity—because there are so many obvious things that need to be checked, to get confidence in this,” Felgner said. “And we don’t have those answers yet.”
Still, those answers are coming. Felgner’s team is planning to survey healthcare workers over time for a constellation of antibodies. The goal is to compare these antibody fingerprints to symptoms to understand why some get severe disease, and others escape relatively symptoms-free.
Inaccurate tests could put people at risk if the results indicate that someone has antibodies, when in fact, they don’t—a result known as a false positive. That could happen if a test detects antibodies against other coronaviruses, like the ones that cause colds, and misinterprets them as antibodies against the novel coronavirus.
“So suddenly you’re getting a lot of positives where you shouldn’t, and people falsely think they’re protected,” Norris said. “That would be the worst-case scenario.”
That’s why researchers around the state are carefully vetting which tests to use. Nam Tran, associate professor and senior director of clinical pathology at University of California, Davis, said his team is working with a Southern California company called Diazyme to develop an in-house antibody test.
“I’ve received over 100 emails from numerous manufacturers—some I’ve never even heard of before,” Tran said. “You don’t want to jump on it out of desperation and have a bad test. Can you imagine I tell a patient or an employee ‘Oh, you’re immune to COIVID-19,’ and it turns out they weren’t weren’t? We can’t do that.”
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