Serology testing is becoming a new pandemic buzzword, at the center of many of the most ambitious and reputable recovery plans. A report by Scott Gottlieb, former Food and Drug Administration commissioner under President Trump, highlights the blood-based tests as an important way to reopen society. So does a plan from Ezekiel Emanuel, one of the architects of the Affordable Care Act under President Barack Obama. In late January, Tom Inglesby of the Johns Hopkins Center for Health Security called for “urgent serology development programs” in case the coronavirus could not be contained.
The theory is that such testing could be used to divide the world into people who’ve had it and aren’t at risk anymore — and those who are. Health-care workers with immunity could return to the front lines. Large employers could test their workers to find out who could return to work first. Health insurers might use the tests to tell members whether it is risky to go out into the world. People who know they have a level of immunity could help others. In the Ebola outbreak in Congo, survivors played a special role in providing care — and much-needed human contact — to people who were sick.
“This is going to be a very valuable portion of the population,” said Gigi Gronvall, a senior scholar at the Center for Health Security. “They are people who are presumably protected, and can volunteer. They can have important roles if they have jobs that are critical — they can have that job, they can declare they’re not going to suddenly come down with coronavirus.”
Figuring out how much of the population has fought off the virus and whether they truly are immune — and for how long — will be essential for informing sweeping, long-term decisions about when to lift stay-at-home orders, reopen schools and resume business as usual. And it could also be a targeted way to safely restart normal life sooner.
Germany has said it will start looking for disease-fighting antibodies in a study of 100,000 people, and could issue certificates that indicate someone has immunity. Gronvall said she has been considering several ideas, perhaps armbands that declare immunity or something like the “Carte Jaune,” the yellow slip of paper that people carried in their passports to assure countries they had received key vaccinations.
But experts on testing warn that these new serology tests come with logistical and scientific challenges just as big, if not bigger, than the ones that made the scale-up of diagnostic testing for active infections so difficult. The mass deployment of blood-based testing will require many millions of accurate tests, a system to take reliable samples, and a slew of decisions that may have to be made based on incomplete knowledge. Will a certain level of antibodies be necessary to declare someone likely to be immune? How lasting and complete will that immunity be? When is the best time to start doing such tests, given that many who are tested today and have no evidence of exposure to the virus may be infected tomorrow? And how will people declare their immunity status?
The uncertainties come as companies have already begun to jump in, offering these antibody blood tests while diagnostic tests based on deep nasal swabs for acutely ill people are still in short supply — almost guaranteeing confusion about how the serology tests should be used.
Elitza Theel, an associate professor of laboratory medicine and pathology at the Mayo Clinic in Rochester, Minn., said that serology tests should not be used for people who have symptoms now. That’s because the tests don’t detect the virus directly, but an immune response that may take eight to 14 days to develop. A person who is a few days into the illness may test negative and be falsely reassured.
Kelly Wroblewski, director of infectious diseases at the Association of Public Health Laboratories, said that one of the biggest concerns about the serology tests that will be offered in the coming weeks and months is the possibility that they haven’t been vetted well enough to know whether they are triggered by antibodies for other illnesses, leading to “false positive” results.
The FDA announced that it “does not intend to object” to the distribution of such tests, so long as they carry warning statements that they have not been reviewed by the FDA and can’t be used as the sole basis to make a diagnosis.
The evidence about what to tell people about their immunity is still uncertain.
“The ideal situation is maybe we test everyone and those people that have developed immunity, we assume have protective immunity and can go back out into the workforce,” Theel said. “I think that’s a possibility, but one of the questions that remains is: Just because you have antibodies, doesn’t necessarily mean they’re at a protective level. That’s something we need to look at and evaluate — and what that protective level is, I don’t think we know that either.”
Florian Krammer, a professor of microbiology at the Icahn School of Medicine at Mount Sinai in New York, created a serology test and is working to supply other labs with a necessary component to stand up such testing at other laboratories. Although it isn’t clear how long-lasting or complete immunity is, he said that based on other coronavirus infections — including with coronaviruses that cause common cold symptoms — people who have had it are likely to be protected.
One small study of a common cold-causing coronavirus in 1990 found that people could be reinfected after a year, but did not develop symptoms. Other studies have documented that antibodies for severe acute respiratory syndrome (SARS), another type of coronavirus, persisted for two years and then declined by three years.
“That doesn’t mean you’re not immune anymore, it means antibody levels are going down,” said Krammer, who added that looking at other coronaviruses, he thinks people could be immune to the novel coronavirus for about one to three years.
Logistical questions remain about who would scale up testing — which could be federal or state governments, insurers or even employers eager to get employees back to work.
One model for how the screening could be used is being tested in Telluride, Colo., where United Biomedical is offering serology tests to all 8,000 residents of San Miguel County. Positive results will be treated as presumptive active infections and health officials will recommend self-isolation for 14 days, said Susan Lilly, public information officer for the county. Those people will be directed to get the nasal swab test that is being used widely across the United States to confirm infection.
Telluride is home to Mei Mei Hu and Lou Reese, the married co-chief executive officers of UBI, a privately held New York-based biopharmaceutical company that develops immunotherapeutics and vaccines for chronic and infectious diseases.
“Our goal is to test the whole county and see the prevalence, who is infected, who has already been exposed to it,” said Hu, who said she thinks it is the first community-wide testing effort. The company is offering the test free, and screening is voluntary. It plans to offer the test to other “hot spots,” she said.
Everyone who is tested will be asked to return in two weeks to take a second test that will show how their immune response has evolved.
The tests should provide “the ability to know how many people have been exposed to the coronavirus and developed immunity,” said Reese, adding that those people then can help deal with the crisis without worrying about being infected.
But there isn’t a guidebook to follow for when and how to roll out such testing more broadly.
“I think a lot of groups are trying to figure that out right now,” Marc Lipsitch, an epidemiologist at the Harvard T.H. Chan School of Public Health, said at a news conference last week. “We’ve never had quite this situation.”
Wroblewski, of the public health laboratories, said she was aware of a few state public health labs in hard-hit areas, such as New York, beginning to develop their own serology tests. She added that the idea of using such testing to reopen society in an organized way was intriguing and might work in theory, but one of the problems is that testing isn’t a magic bullet. It provides information that can inform decisions about how to respond in a coordinated way — which will be the job of those leading the response.
“The reality is, and what’s been somewhat frustrating throughout the whole response, is the idea that more testing is going to solve problems, solve the outbreak,” Wroblewski said. “Testing really provides information, and that’s all it does — it doesn’t stop viruses from transmitting. You still have to enforce the same public health measures, the stay-at-home orders and everything else, and people have to follow them for lab data to do anything effective.”