Antibodies tests deemed vital are seen as flawed
A law firm in Scottsdale, Ariz., tested employees who hoped, with the prick of a finger, to learn if they might be immune. In Laredo, community leaders secured 20,000 of the new tests to gauge how many residents had been infected.
In recent weeks, the U.S. has seen the first rollout of blood tests for coronavirus antibodies, widely heralded as crucial tools to assess the reach of the pandemic in the nation, restart the economy and reintegrate society.
But for all their promise, the tests — intended to signal whether people may have built immunity to the virus — are already raising alarms.
Officials fear that the effort may prove as problematic as the earlier launch of diagnostic tests that failed
to monitor which Americans, and how many, had been infected or developed the disease the coronavirus causes. Criticized for a tragically slow and rigid oversight of those tests months ago, the federal government is now faulted by public health officials and scientists for greenlighting the antibody tests too quickly and without adequate scrutiny.
The Food and Drug Administration has allowed about 90 companies, many based in China, to sell tests that have not gotten government vetting, saying the pandemic warrants an urgent response. But the agency has since warned that some of those businesses are making false claims about their products; health officials, like their counterparts overseas, have found others deeply flawed.
Tests of “frankly dubious quality” have flooded the U.S. market, said Scott Becker, executive director of the Association of Public Health Laboratories. Many of them, akin to home pregnancy tests, are easy to take and promise rapid results.
And the federal guidance that does exist is so confusing that health care providers are administering certain tests unaware that they may not be authorized to do so. Some are misusing antibody test results to diagnose the disease, not realizing that they can miss the early stages of infection.
“People don’t understand how dangerous this test is,” said Michael Osterholm, an infectious disease expert at the University of Minnesota. “We sacrificed quality for speed, and in the end, when it’s people’s lives that are hanging in the balance, safety has to take precedence over speed.”
Even as government agencies, companies and academic researchers scramble to validate existing tests and create better ones, there are doubts they can deliver as promised. Most tests now available
mistakenly flag at least some people as having antibodies when they do not, which could foster a dangerously false belief that those people have immunity.
And even if the tests do improve, their availability could be hampered by the same manufacturing shortages that have prevented the COVID-19 diagnostic tests from scaling up adequately.
As President Donald Trump presses to reopen the country and several states consider lifting lockdowns in the next few weeks, widespread screening is considered critical.
Epidemiologists are testing for antibodies in hot spots to better measure the extent of the outbreaks, and government officials intend to use those results to help decide when and how to return residents to daily life. But many scientists and political leaders say the country is nowhere close to deploying enough diagnostic and antibody tests at the speed and volume required.
Recent testing around the country demonstrates the challenges of using the new products.
Soon after it helped screen the Rose Law Group, the firm in Arizona, a lab stopped providing rapid tests to other clients, fearing that they might not comply with federal guidelines, and switched to more sophisticated lab-based tests.
In Laredo, officials discovered that the tests they received were woefully inadequate. The local health department found them to have a reliability of about 20 percent, far from the 93 percent to 97 percent the company had claimed. A police investigation led to a federal seizure of the tests.
Easiest, most unreliable
More than 90 companies have jumped into the market since the FDA eased its rules and allowed antibody tests to be sold without formal federal review or approval.
Some of those companies are startups; others have established records. In a federal guidance document March 16, the FDA required them to validate their results on their own and notify the agency that they had done so.
Their products vary. Some test only for a transient antibody that spikes while the body is in the throes of an active infection. Another antibody, which peaks about four weeks after infection and marks longer-term immunity, is a separate target. There are tests that look for both antibodies; others also look for a third involved in respiratory infections.
The most reliable ones involve a laboratory technique called Elisa that can indicate the amount of antibodies a person may have. Researchers are not certain that people who have recovered from COVID-19 have immunity, though it would follow the usual pattern for viral infections. Higher levels generally mean a stronger physiological response, but it is unclear what levels are needed for immunity to the new coronavirus — or how long it might last.
“We’re really far from that,” said Osterholm, the disease expert. “We’re not even in the second inning of a nine-inning game at this point.”
Most of the tests offered are rapid tests that can be assessed in a doctor’s office and provide simple yes-orno results. Makers of the tests have aggressively marketed them to businesses and doctors, and thousands of Americans have already taken them, costing a patient roughly $60 to $115.
Rapid tests are by far the easiest to administer. But
they are also the most unreliable — so much so that the World Health Organization recommends against their use.
This month, the FDA warned that some companies marketing their antibody tests in the U.S. were falsely claiming that they had formal federal approval or that they could diagnose COVID-19.
In an effort to speed up access, the FDA apparently did not fully consider how these tests would be administered. The agency released a guidance document saying that antibody tests could be performed at “point-of-care” settings, indicating that doctors, nurses and others could give them to patients in their offices. But agency officials also acknowledged that under federal law, if a test has not been authorized by the agency, it must be conducted in so-called high-complexity laboratories, such as some large commercial facilities or public health labs. The officials declined to provide additional clarification.
“If you are getting an antibody test, and it’s being conducted in your physician’s office, it’s a red flag,” said Kelly Wroblewski, director of the infectious disease programs for the Association of Public Health Laboratories.
The FDA has received requests for emergency use
authorization from 120 antibody-testing developers. So far, it has granted formal approval to just four: Cellex, Ortho Clinical Diagnostics, Chembio Diagnostic Systems and the Mount Sinai Laboratory.
False positives
While political leaders and some health officials say that antibody testing will be essential to reopening the country, it is unlikely to meet expectations anytime soon.
Less than 5 percent of the U.S. population may be infected, and even in hot zones such as New York or New Orleans, the prevalence may not be higher than 10 percent to 15 percent, according to Osterholm. When the proportion of people exposed is that low, the tests’ false-positive rate — signaling antibodies where there are none — can limit the tests’ utility.
Researchers at the National Institutes of Health are validating some of the tests in cooperation with the FDA. This month, a Danish group published a small analysis of nine tests and found, as might be expected, that some performed better than others. A research group backed by the Chan Zuckerberg Initiative is working to assess all available tests using the same set of samples for each, with early results expected next week.