Lindsay Liebig was driving the winding roads of rural Vermont with her 4-year-old son strapped in the backseat when she got the call. Despite having no symptoms, she’d tested positive for the coronavirus.
“So that was anxiety-inducing,” said the 35-year-old, who got tested after her son spiked a fever. “I accepted that I had coronavirus and was like, well [damn], I gotta make some phone calls here.”
Liebig would ultimately be one of 65 people who tested positive last week after completing the rapid antigen test offered at a private medical clinic in the heart of Manchester, Vt., a town of fewer than 5,000. News of an outbreak set off alarms in a state that to-date had fared well in the pandemic, registering the second-fewest cases in the country. Many local restaurants and retailers quickly shut down. The Saturday farmers market was canceled. State officials with little information scrambled to answer questions from reporters and the public as to how and where the outbreak began.
But in Vermont, positive antigen tests — a relatively new way of detecting an active COVID infection — require confirmation by another test: a polymerase chain reaction, or PCR, test, the gold-standard used by the government, hospitals, and professional sports teams. Of the 65 people who’d received those positive antigen tests, 48 would ultimately test negative via PCR. Liebig was one of them.
A community on edge was now a community confused. Had there been an outbreak? The state’s health department said no, while the clinic stood by its findings that showed positive test results. The Manchester town Facebook forum erupted with questions about antigen testing, authorized in May by the FDA for emergency use. What to make of this apparent testing stalemate?
Attempts at answering that question proved to be a lesson in the current fractured state of testing in the United States as well as a reminder of how little is still known six months into the pandemic about the coronavirus and the methods used to mitigate its spread.
Antigen testing, which also requires a nasal swab but can return results in just 15 minutes, has been heralded as a cheap and speedy alternative to the cumbersome and pricey PCR tests, which in the United States can take anywhere from a day to two weeks to process. Rather than lugging vials off to a lab where they’re heated, cooled, and spun, antigen test cassettes are inserted into a small on-site machine that quickly reads the results.
But although the antigen test was recently authorized by the Food and Drug Administration, it is not formally approved, meaning only a handful of studies — submitted by the very companies that markets the product — have been completed to verify its reliability.
“It’s amazing how little the FDA requires for an emergency-use application,” said Dr. David Hamer, an infectious disease expert at Boston University and a physician at Boston Medical Center. “To me, the antigen test is just not ready for prime-time use, especially to identify individual infections.”
Given the danger the virus poses, the government has tried to move quickly to provisionally approve new medical products that could help ameliorate shortages and mitigate the spread of the virus. Other devices that have been authorized, but not officially approved, include face masks and ventilators, as well as PCR tests from companies such as Abbott.
Unlike PCR tests, which detect the presence of genetic material, antigen tests detect specific proteins on the surface of a virus. In May, the rapid antigen test for COVID-19, made by the San Diego-based Quidel, became the first of its kind available for public use. A second product, made by New Jersey company Becton Dickinson, also received authorization in July. The Manchester clinic uses the Quidel test.
Quidel completed just three studies on its product, all involving frozen samples, before requesting authorization. A package insert for the product warns that “performance may be different with fresh samples.” Such sparse data is typically insufficient for public use, but the federal government’s Emergency Use Authorization authority allows unapproved medical products to be used in public health emergencies when no approved alternative is available.
“We don’t have any independent validation on these antigen tests,” said Dr. Gigi Gronvall, a biosecurity expert at the Johns Hopkins Center for Health Security. “Often those studies come out differently from those of the manufacturer. It’s just they don’t have access to the volume of samples necessary to do thorough testing.”
But even the limited studies have shown sensitivity to be the test’s Achilles’ heel, meaning sometimes the test produces false negatives. In one study, 20 percent of positive COVID cases were missed. Typically, the false negatives stem from those with smaller viral loads, who are not overly contagious at the time of testing.
Still, this noted lack of sensitivity does not explain what went awry in Vermont. It’s possible that the clinic received a faulty batch of tests or the processing machine malfunctioned. Quidel has sent a representative to Manchester to oversee and investigate operations, according to Bill Sklar, a spokesman for the company. The Manchester Medical Center maintains it followed protocol while running the tests, while the Vermont health department is treating the results as a cluster of false positives.
“At this time, there is nothing to indicate a failure of the Quidel test system,” said Sklar. “We don’t want to get ahead of the facts in Manchester, but we will work tirelessly with authorities there to determine the truth and respond accordingly.”
But not every state categorizes the results that way. In fact, the way each state observes positive antigen tests speaks to the disjointed nature of the nation’s pandemic response, despite its porous state borders and roving population. Rhode Island and Massachusetts include positive antigen tests in their daily case total, while Vermont and New Hampshire require confirmation via PCR. New York, where Liebig lives, is treating her as a presumptive positive case for COVID and mandating quarantine, despite her negative PCR test.
Liebig is relatively certain she’s negative since she has shown no symptoms herself and no one around her has reported symptoms. But she worries this testing debacle and the tussle between the clinic and the state only exacerbate a skepticism of testing systems.
“I got tested because I wanted to err on the side of caution, but this incident definitely makes me question the numbers to some degree,” she said. “It feeds all the conspiracy theories that this is some sort of political machine out to stop Trump from being elected. It’s all very frustrating.”
Regardless, some experts maintain that the clinic probably shouldn’t be administering the test in the first place. Dr. Janel Kittredge, the owner of the Manchester clinic, told the Manchester Journal she opted to purchase the antigen test after having difficulty obtaining PCR test kits. Other private practices across the country are doing the same, in part due to the shortages and in part due to the low price of the antigen test, which they can make a quick profit off of.
Manchester Medical center charges $65 a swab for an antigen test, while PCR tests are generally offered for free. In Massachusetts, CareWell Urgent Care clinics offer both PCR and antigen tests for $160 each but warn that the former may now take 10-14 days to process.
But the rapid antigen test is most effective when performed on a large group of individuals on a near-daily basis. Each person would have an up-to-date idea of their infection status and, even if the test misses a few cases, it would likely identify the most contagious in the bunch. PCR tests, by comparison, are quite accurate but can take days to return results, rendering them obsolete since a person could have become infected in the interim period.
Until there is a vaccine, testing is widely seen as the greatest tool in containing future infections and allowing a return to normalcy. Some infectious disease doctors see the antigen test as the key to opening the door to a reality where students could be screened before each school day or fans before each sporting event. The Trump administration announced a small step in that direction last week via a plan to provide nursing homes in hard-hit areas with a limited supply of antigen tests to test residents and nurses on a weekly basis. Massachusetts officials are not aware of any Massachusetts nursing homes receiving such aid, according to the state’s health department.
“If only the federal government would perfect them slightly and then produce them in the hundreds of millions or billions, you could practically stop transmission overnight,” said Dr. Michael Mina, an assistant professor of epidemiology at the Harvard T.H. Chan School of Public Health. “There is a whole new world to be had.”
Hanna Krueger can be reached at firstname.lastname@example.org. Follow her on Twitter @hannaskrueger.