WASHINGTON — With President Trump and many others eager to see the country recover from the coronavirus, antibody tests are emerging as a crucial marker of just how prepared the nation is to lift restrictive measures that have kept about nine out of 10 Americans under lockdown for weeks.
Those tests have been quickly brought to market, with maximum speed and minimum oversight, recalling the disorganized rollout of diagnostic tests throughout March. And this time around, the near-total absence of federal regulation could result in the American market being flooded with tests that one former director of the Centers for Disease Control and Prevention described as “junk.”
There are now 110 different corporations and laboratories offering coronavirus tests, but only four of those tests have been vetted by the Food and Drug Administration under Emergency Use Authorization guidelines, which can expedite approval of medical products during a public health crisis.
Lockdowns have so far slowed the spread of the coronavirus, which has infected 722,000 Americans and resulted in more than 34,000 deaths. Although infections and deaths are continuing, Trump said last Thursday some states could begin to lift measures that have brought the American economy to a virtual standstill.
Antibody blood tests will be an important aspect of that effort. Those tests can reveal who has already been infected with the coronavirus and whether they showed symptoms at the time. The nasal-swab tests that have been administered to more than 3 million Americans are meant to tell people they are sick, whereas antibody tests are able to tell them they had been sick earlier and (presumably) don’t have to worry about becoming sick again.
Reliable antibody testing could, therefore, be a key aspect of reopening the country.
“Antibody testing is very important. It’s just that it needs to be done right, so that it improves the effort against COVID-19,” says Dr. Mark Birenbaum, director of the National Independent Laboratory Association, a group that represents many smaller laboratories around the country.
In other words, the tests have to be accurate in order to be useful.
Antibodies are proteins deployed by the immune system against disease. When found in the bloodstream, they indicate that a person is either fighting off or has recently fought off a disease, and can confer immunity against future infection. Some nations have considered so-called immunity passports that would authorize those who have recovered from COVID-19, the disease caused by the coronavirus, to return to work.
Doctors believe that people who contracted a coronavirus infection and then cleared the virus from their systems are immune, at least for a period of time, although the scope of that immunity remains a point of intense debate in the medical community.
In addition, people who have recovered from COVID-19 can donate their blood plasma to be harvested for antibody-rich convalescent serum, which can then be used to treat other patients.
But if the antibody tests give false results, they could actually severely hamper a return to normal.
Right now, 106 of the 110 tests being marketed in the United States have not gone through the external validation process pharmaceutical companies are subject to. And many of the unauthorized manufacturers are based in China, where biosecurity has long been a concern. Patients will simply have to hope that LifeAssay Diagnostics (Cape Town, South Africa), Euroimmun (Lübeck, Germany) and Lepu Medical Technology (Beijing) are responsible marketers of their products.
The lack of regulation and organization could present an opening to unscrupulous operators. In fact, it already has. Florida-based CoronaCide is suing a California company, the Wellness Matrix Group, for reselling its antibody tests as home kits. The tests were intended to be used specifically in medical settings.
“The FDA has been very cautious about the antibody tests,” Dr. Deborah Birx, response coordinator of the White House coronavirus task force, said at a briefing last week. Birx then referred to reports of other nations experiencing high error rates in their antibody tests. “You never want to tell someone that they have an antibody and potential immunity when they don’t,” Birx said.
At that same briefing, Trump celebrated the authorization of two antibody tests by the FDA. Missing was context — that while there are four tests that do have such authorization, there are 106 that do not.
The problems already evident in the rollout of antibody tests by private companies like CoronaCide and Euroimunn, and the federal government’s receding oversight of that process, recall the delays, errors and disorganization that dogged the implementation of diagnostic tests throughout February and March. The experience of other nations suggests that more aggressive testing in the early stages of the pandemic could have reduced its eventual spread. Testing in later stages of a pandemic could keep it from coming back.
If those tests are even accurate.
“These tests create more uncertainty than before,” infectious disease specialist Kelly Wroblewski of the Association of Public Health Laboratories told reporters last week. Her group represents state-run laboratories, none of which are yet using antibody tests.
Approved tests are coming. The first test approved under the Emergency Use Authorization was developed by the North Carolina-based company Cellex and manufactured in Suzhou, China. But it has not yet been available in the United States because Chinese customs officials have held up exports of the tests, a company representative told Yahoo News.
“They are quite hopeful that they will receive clearance to ship next week,” the Cellex representative said.
The other tests have been granted what amounts to blanket approval under a March 16 guidance from the FDA that said antibody tests, also known as serology tests, did not immediately require the same Emergency Use Authorization certification that Cellex asked for and received. The other manufacturers were encouraged to obtain a certification but could still sell their tests in the U.S. without one.
The guidance appeared to signal a recognition that greater testing capacity is desperately needed if the United States wants to follow Germany’s path out of the pandemic. In that country, antibody tests have helped chart the course.
But whereas Germany was prepared to test its population for the virus, the U.S. — with four times as many people — was not. Desperate to catch up, the FDA needs what help it can get from the private sector, and it is willing to cede some of its regulatory power for the sake of speed. Hence the March 16 guidance says that tests “should be validated prior to use” but does not make that validation mandatory.
While there could be obvious legal consequences for a company that peddles faulty tests, for now the federal government is tacitly sanctioning the sale of such tests. Because those consequences are so obvious, the FDA appears to be calculating that most corporations that have the know-how to market a coronavirus antibody test will know better than to attempt profiteering during a public health crisis.
The guidance additionally “recommends” that manufacturers make clear in their marketing that the government has not approved their tests. But again, they are not required to.
Claiming the imprimatur of the federal government could be an attractive way to gain a competitive edge in a crowded market. Wellness Matrix Group, the California company accused of misrepresenting antibody tests as suited for home use, had its stock suspended from trading by the Securities and Exchange Commission earlier this month because of assertions “made through affiliated websites and a company consultant about selling at-home COVID-19 testing kits that had been approved by the FDA.”
Large institutional entities will probably buy their tests from like-sized vendors. Some, like the Mount Sinai Medical Center in Manhattan, will even develop their own antibody assays. But both demand and supply are high enough, and oversight hands-off enough, for disaster to strike.
“The problem is that we don’t know what the rates are for any of these kits when used ‘in the field,’” Birenbaum of the National Independent Laboratory Association wrote to Yahoo News in a text message. “So how can we pick the best to use to slow the spread of the COVID-19 virus?”
Birenbaum said that while some of his member laboratories have discussed implementing antibody tests, they have been hesitant to do so. “Our labs are all CLIA-certified,” he told Yahoo News, using the acronym for a set of regulations known as Clinical Laboratory Improvement Amendments, adding that members of his association “only use tests that meet CLIA requirements.” None of the tests currently on the market appear to meet that certification.
The skepticism was validated by a brief on serological testing published last week by the American Clinical Laboratory Association, which represents some of the biggest corporate laboratories in the nation (Birenbaum’s group, NILA, tends to represent smaller labs). That brief identifies several problems, including supply chain bottlenecks and the proliferation of incorrect results.
“To ensure that the U.S. can reopen and stay open for business, the federal government must play the leading role in scaling up and financing widespread SARS CoV-2 serologic testing,” the association said, using the formal name of the coronavirus pathogen.
The financing issue has seemingly been resolved, with the Trump administration saying that the cost of the tests should be covered. But scaling up, and doing so with a commitment to testing accuracy, has presented a challenge.
Diagnostic testing got off to a slow start in the U.S. in part because the CDC insisted on creating its own assays, instead of using the ones that had been developed by the World Health Organization and successfully deployed in China. The CDC-created test was faulty, and fixing it took several weeks.
The Trump administration eventually lifted restrictions on who could manufacture and deploy diagnostic tests, falsely asserting that those measures had been put in place by the Obama administration. With the antibody tests, however, medical experts fear federal officials may have erred in the other direction, letting private industry decide virtually every aspect of the antibody testing regime.
An official working on the White House coronavirus response told Yahoo News that “the Task Force is aware of the quantity of tests, and is in the process of developing distribution concepts that will assist in moving our country and economy forward. Test quantities are shared on a confidential basis by the manufacturer.”
But that official would not say whether a single task force official was working with private companies to coordinate where those antibody tests were going. Because so many companies have been permitted to sell antibody tests, such coordination would be extremely difficult.
The federal government is also scrambling to collect data on the tests that are already in use. FDA spokesperson Stephanie Caccomo told Yahoo News that “serology test developers should notify FDA that they have validated their tests, even when they do not provide validation or accuracy data at this time to the FDA. Developers also should include certain disclaimers on any results generated by their tests.”
Caccomo added that the FDA is working with the National Institutes of Health, the Biomedical Advanced Research and Development Authority and the CDC to “rapidly evaluate the performance characteristics of these tests.”
The situation could improve as large corporate laboratories create antibody tests of their own. Even without federal guidance, they have the institutional resources to create safe, reliable tests. Biomedical giant Abbott Laboratories is in the process of shipping 4 million of its own antibody tests, company public affairs manager Shelley Lange told Yahoo News, adding that Abbott expected to have 20 million antibody tests available to the public by June.
Mayo Clinic Laboratories, another leader in the field, is also expected to introduce its own antibody test soon, with a projected capacity of 8,000 tests per day.
But for now, the antibody testing landscape is a free-for-all, where profits compete with well-intentioned public health imperatives. That tension even worries the FDA, whose March 16 announcement that private companies could proceed without federal approval largely created the current scenario.
“I am concerned that some of the antibody tests that are on the market that haven’t gone through the FDA scientific review may not be as accurate as we’d like them to be,” FDA Commissioner Stephen Hahn said on “Meet the Press” last week, without mentioning that those tests did not have to go through an FDA review because the agency waived the review process.
And whereas both state and private laboratories clamored for diagnostic tests for much of February and March, both are now staying away. There are now antibody tests being offered in Seattle — where the coronavirus epidemic began in the U.S. — according to city spokesperson Chelsea Kellogg. New York City, which has been devastated by the disease, has only Mount Sinai, the Manhattan hospital, conducting antibody testing.
It is impossible to say whether that discrepancy represents a wariness on the part of public health officials, disorganization on the White House coronavirus task force, snags in the biomedical supply chain or a combination of all three factors.
The greatest worry is that the tests incorrectly tell people they are immune from the coronavirus (a false positive) or fails to detect that they do have antibodies to the disease (a false negative). That could unduly frighten people or give them a false sense of security.
“We can’t really afford to spend a lot of resources on trying to make heads or tails out of what will turn out to be not-good data,” Association of Public Health Laboratories program director Eric Blank warned last week. “We can’t really rely on those 90-odd tests that FDA has on that list.” (The number of tests on that FDA list has grown by about two dozen since Blank made those comments.)
That concern has evidently been confirmed by reports from South Korea that an antibody test widely deployed there has been giving inaccurate results. That is the situation public health officials in the U.S. are desperate to avoid. And that is why many state and private laboratories are staying away for now, even if antibody testing is a tantalizing tool that could help America beat back the coronavirus.
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