Inaccurate results from rapid COVID-19 tests raise concerns about widespread screening
Dozens of people who took quick-result coronavirus tests at a Manchester, Vermont, clinic in July were told they had the virus, only to be informed days later that more accurate lab tests concluded they didn't.
Last week, Quidel, the company that makes the rapid antigen test used by the clinic, stood by the original results. The top executive said it's "highly likely" his company's test was correct, and the state of Vermont's conflicting lab-based test was "at risk of providing inaccurate results."
As companies and universities create their own strategies to widely test employees and students – even those with no symptoms of COVID-19 or no known exposure to the virus – experts warn such confusion over conflicting results is inevitable.
Widespread testing can identify people who have the virus and halt the spread of some new cases. But because no test is infallible, some cases will be missed, and some people will be forced to miss work after false positives.
Ohio Gov. Mike DeWine said this month he tested positive on a rapid diagnostic to detect the COVID-19 virus before he was to greet President Donald Trump at a Cleveland airport. Two follow-up tests using a more precise, lab-based test showed the governor didn't have the virus.
In Maine, 19 summer campers tested positive last month using a rapidantigen test, only to be cleared by the state's lab test, the Bangor Daily News reported.
It's a scenario that will "come up over and over again," said Jennifer Nuzzo, a senior scholar at the Johns Hopkins Center for Health Security.
"We are going to blanket the country with tests," said Nuzzo, an associate professor at the Johns Hopkins Bloomberg School of Public Health. "A lot of the push around testing has really been approached from a tech-forward perspective with a goal of trying to reopen our economy and not necessarily thinking through what the consequences are."
Without a vaccine to prevent COVID-19, the nation has relied on testing to identify who has the virus and must be isolated. Everyone else is urged to keep their distance from others, wear masks and wash their hands.
Assistant Secretary for Health Brett Giroir said the USA should have up to 90 million tests in September – an average of about 3 million tests each day. As many as 40 million tests will be "point of care" tests with rapid results.
The Food and Drug Administration granted emergency use authorization to three rapid antigen test manufacturers to diagnose COVID-19: Quidel, LumiraDx and Becton, Dickinson.
The Trump administration invoked the Defense Production Act last week on federal contracts with Quidel and Becton to expedite production of antigen testing machines that can provide immediate results for 14,000 nursing homes. The effort "is our highest priority to save lives," Giroir said.
The National Institutes of Health issues grants through a $1.5 billion "Shark Tank"-style competition called Rapid Acceleration of Diagnostics. The goal is to bring capacity up to 6 million daily tests by December.
Lab experts worry the push to test millions of Americans every day, without policies on how to use and interpret results, could confuse people who get conflicting answers, as it happened at the Vermont clinic.
PCR tests detect the virus's genetic material. They find even low levels of the virus, so they have been the diagnostic test for public health and clinical labs since the beginning of the pandemic.
Antigen tests detect specific proteins on the surface of the virus. Testing materials are cheaper and more plentiful, and the tests are fast, delivering results in 15 minutes. They're less sensitive than PCR tests and more likely to miss a case.
Because no test is always accurate, doctors who analyze test results must consider other factors, such as how widespread the virus is in a community. If someone tests positive but shows no symptoms, has no known exposure and lives in a community with relatively few cases, it's difficult for a doctor to interpret that result.
"The false negative and false positive rates for any test are never zero," said Dr. Dwayne Breining, executive director of Northwell Labs.
Quidel, Vermont spar over results
On July 1, an 18-year-old on a family vacation from New York, who had displayed symptoms for four days, tested positive at Manchester Medical Center in Vermont. Five more people tested positive July 10. Those initial cases emerged during the town's busy tourist season, potentially infecting others at gatherings such as barbecues, soccer games, restaurants and bars.
Through July 17, 64 people tested positive and about half of them had symptoms, said Janel Kittredge, Manchester Medical Center's chief medical officer and owner.
The clinic faxed the results of each positive antigen test nightly to the Vermont Department of Health. For a case to be listed as official, Vermont requires confirmation with a PCR test.
The state Health Department said it could confirm just four cases from the Manchester clinic. The state set up a pop-up clinic to test hundreds of others before concluding there were no signs of an outbreak.
San Diego-based Quidel said it conducted its own investigation and found no issues with the clinic or the company's tests. It shared results with the state Health Department, the U.S. Centers for Disease Control and Prevention and the FDA.
The FDA informed Vermont it found no issues with Quidel's instruments or how they were used, the Vermont Department of Health said.
It's unclear what information the FDA reviewed, but a spokesman said no recall is warranted and the agency is "continuing our evaluation."
Vermont Health Commissioner Mark Levine said Friday it was inappropriate for the Quidel executive to question the accuracy of the state's PCR test. His agency said PCR "remains a very reliable test" and people should be confident in its results.
Schools, camps grapple with false results
Discrepancies among different testing methods are common in the lab industry.
The difference with COVID-19 is the nation has never attempted to test such a large portion of the population. Never have such large groups of Americans been ordered to quarantine based on test results.
"If you test enough people, you will get a false positive; you will get a false negative with any test," Breining said. "And the question is now, what are going to be the consequences of it? How do you manage it?"
Breining said his son attends a school in Manhattan with about 3,000 students. One proposal for New York City schools would require all students in a classroom to quarantine if one tests positive. If a student in another classroom tests positive, the entire school would shut down for two weeks.
Routine, inexpensive testing of New York City students, teachers and staffers would allow schools to quickly identify new cases. Schools would sometimes close based on test results that might be inaccurate.
The key is to develop policies that require a confirmation test to gauge whether the initial test is accurate, Breining said.
The Maine Health Department did not identify the summer camp with 19 false positives, but other camps took notice.
Camp Modin, which served about 360 kids from New York, New Jersey, Connecticut and other states, concluded camp without a single case. Organizers met with epidemiologists for months to carefully plan multiple rounds of testing, cleaning protocols and who would be allowed on the grounds.
Campers were tested three times – a lab test before they arrived, a rapid test at the camp and another lab test days later. One camper tested positive after arriving, but medical staff concluded it was a false positive after the child was tested seven times. Nevertheless, the child was isolated in a medical unit until there were no signs of COVID-19.
The camp operated as a bubble without allowing anyone in or out. Staff arrived two weeks before the start of camp and also underwent three rounds of tests.
“Everyone bought into it,” said Howard Salzberg, the camp’s executive director. “Ironically, this is the healthiest summer we’ve ever had.”
Positive results mean caregivers must take unpaid leave
Inaccurate results could harm caregivers or nursing home assistants who take care of vulnerable patients.
"Clearly, the example of a nursing home, we would want to know very quickly if somebody is bringing the virus in there," Nuzzo said. "But there are also consequences to inaccurately identifying somebody who has to stay home and is unable to work, possibly putting patients at risk because of the shortages in the workforce."
Sherry Perry, a certified nursing assistant, works in a nursing home and has a second job as a home health aide.
The Lebanon, Tennessee, resident agrees testing is vital to protect vulnerable residents and health care workers. But she said it's financially devastating when nursing assistants must take unpaid leave when they test positive, despite questions about the accuracy of some tests.
Perry had to take a week off work after a co-worker tested positive. She was not paid but had enough savings to tide her over. Other colleagues struggle.
"Most CNAs (nursing assistants) are living check to check," said Perry, who is co-chair of the National Association of Health Care Assistants.
Some nurses use vacation time and sick days during quarantine, leaving less flexibility to take time off for other reasons."Our job is not only physical but emotional, too," Perry said. "We get burned out really easily."
Nursing homes in New Hampshire and Texas have reported false positives. In Connecticut, errors at the state lab meant 90 people, including nursing home residents, registered false positives from mid-June through mid-July.
Such inaccurate results can disrupt operations and waste resources. However, industry representatives said widespread testing is critically important to protect residents and workers.
Mark Parkinson, president and CEO of the American Health Care Association and National Center for Assisted Living, said the bigger challenge this summer has been getting timely results to patients and staff.
In July, more Americans sought tests than the nation's labs could process in a timely manner. There are signs that the bottleneck is improving. Two major commercial labs, Quest Diagnostics and LabCorp, said average turnaround times have improved.
Nursing homes need rapid antigen tests to provide quick results to residents and staff, Parkinson said. If test results are inaccurate, nursing homes should retest samples to correct errors.
"You can always retest a positive result to get a confirmation," Parkinson said. "It's accurate to say the antigen tests are not as precise as the PCR tests. But the speed of getting results probably outweighs the disadvantage of their slightly reduced accuracy."
Speed more vital than accuracy?
Some experts want the FDA to loosen oversight of rapid tests that can be taken at home and deliver immediate results, albeit without the sensitivity or accuracy of lab tests.
Michael Mina, an infectious disease epidemiologist at the Harvard T.H. Chan School of Public Health, said more inexpensive, at-home tests will be accurate enough to detect when somebody is infectious.
PCR testing can pick up signs of the virus even when somebody is no longer infectious, he said. That means some people are unnecessarily quarantined after they recovered.
"The travesty is that we’re spending so much time focusing on capturing people over here by mistake that we’re missing the people who are actually infected, and those are the people we really should be quarantining," Mina said.
Dr. Rachel Levine, the Pennsylvania secretary of health, agreed rapid tests at clinics and homes could be an important tool to stop COVID-19. "We’ll see if that is available by the end of this year," Levine said.
Gov. Tom Wolf announced a medical device company, OraSure Technologies, will expand in Pennsylvania and is working to develop a rapid antigen test. The company expects to seek FDA's emergency use authorization by September, aiming to bring the test to the market before the end of the year.
Others said the bigger challenge rests not with the technology but with deciding how to manage and interpret results that are not always correct.
That requires coordination, Breining said, "preferably at the national level, that up until now, we’ve demonstrated we are incapable of doing effectively."
Contributing: Karen Weintraub
Ken Alltucker is on Twitter as @kalltucker or can be emailed at firstname.lastname@example.org