Rapid antigen tests for SARS-CoV-2 are cheap, fast, and easy to distribute. They are not as accurate as molecular PCR tests. However, their popularity—and availability—continues to grow, especially during variant surges. According to a March 2022 Morbidity and Mortality Report from the Centers for Disease Control and Prevention, at-home test use among respondents with self-reported COVID-19-like symptoms increased from the time of delta (5.7%) to omicron (20.1%). They found that of those who used tests, 39.4% did so because of a recent exposure to the virus and 28.9% did because of COVID-19-like symptoms.
“Speed is absolutely crucial when your goal is to do something quickly that improves the effectiveness of a treatment strategy, even if accuracy is a little bit lower,” said Michael Mina, MD, PhD, chief science officer of eMed and former Harvard epidemiologist. “Rapid antigen tests become a much more effective test when we really step back and say, ‘what’s our goal here?’”
New data show that Americans have mixed feelings about rapid tests. They don’t have much confidence in the result, but nevertheless want to stock up. In an Economist/YouGov poll conducted in January 2022, more than 55% said they would be ordering free tests provided by the government. At the same time, only 9% place “a great deal of trust” in at-home rapid antigen tests. This is quite a bit lower than the still not-so-great numbers for PCR: Only 35% have high trust in the results of PCR tests conducted by healthcare workers outside of the home.
Rapid Tests as Part of a Serial Testing Strategy
Rapid antigen tests often have only a mediocre reputation among clinical laboratorians because they are not as accurate as PCR tests. A recent study in Clinical Chemistry found that rapid antigen tests had an analytical sensitivity that varied from 66.5% to 88.3% (2021; doi:10.1093/clinchem/hvab138).
However, while someone who tests too early in their disease course or has an asymptomatic SARS-CoV-2 infection may get a false negative from a rapid antigen test, false positives are rare.
“When you start doing serial testing, the false negativity is mitigated and mitigated well,” said Wilbur Lam, MD, PhD, professor of pediatrics and biomedical engineering at Emory University and Georgia Institute of Technology. Lam is a principal investigator of a center reviewing COVID-19 diagnostic tests for the National Institute of Health’s Rapid Acceleration of Diagnostics (RADx) program. Many countries, including Britain, Singapore, and India, have made rapid antigen tests very inexpensive or free to encourage people to test often as part of their public health response. “They’re pretty useful for a symptomatic person who may be in day one of infection and even more useful if used again the next few days,” Lam said.
Rapid antigen tests are also helpful during surges because they don’t pile onto a sharp increase in demand on laboratory services, said Bradley Karon, MD, PhD, codirector of the point-of-care testing program at the Mayo Clinic in Rochester, Minnesota. If someone who is symptomatic tests positive on a rapid test at home, they may not necessarily need a PCR test run by a laboratory to prove they’re sick, thus freeing up capacity for patients needing molecular COVID-19 testing and other laboratory testing needed in healthcare centers.
“The value of rapid tests increases as the prevalence of disease increases. That’s why there’s been so much focus on rapid antigen tests during the omicron wave. There was more virus transmission than any of the previous surges,” he said.
Rapid Tests for Results Right Now
When considering the usefulness of rapid tests, Mina thinks not just about accuracy but also about what he calls “effective accuracy.” More accurate tests are good, but only if patients and medical professionals can get results quickly enough. Early in the pandemic, PCR test results could take more than a week. In early January 2022, Quest Diagnostics was reporting an average of 2–3 days for PCR results (though that number had dropped to 1 day as of March 20, 2022).
“Laboratories have had a hard time with antigen tests in general, and there’s good reason for that given the accuracy, but it’s about speed and really rethinking the role that test has in the middle of a pandemic for treatment and limiting spread,” Mina said.
He likened rapid antigen tests to frozen section biopsies, which can let surgeons know if cancer, infection, or other diseases are present in a mass in 45 minutes, while surgery is actively happening. “The importance of a frozen section biopsy, even if it’s not as accurate as a fully formed and fixed tissue that we might look at under a microscope in ideal settings, is speed. In the middle of a surgery, you can’t wait 3 days,” he said. Likewise, in the middle of a pandemic, especially during a surge in virus cases, a 15-minute test is going to be more critical than one that takes days.
“If you get results back from a 100% accurate test in 7 days, its effective accuracy is zero,” he said. “If you could get a rapid test that’s 90% sensitive back in five minutes, the effective accuracy is around 90%.”
Karon also pointed to a limit of PCR tests: that they can still turn positive for weeks after a patient has cleared a SARS-CoV-2 infection, which can be particularly distressing or even unhelpful if the patient had never been symptomatic. “Can I go to my family reunion or was this likely to be some time ago and I’m not likely to be infectious?” That doesn’t mean PCR tests have no role in the COVID-19 response, he added, but rapid antigen tests are more useful in these specific circumstances, as they identify someone more likely to have an active infection.
"Test to Treat"
On March 8, the U.S. Department of Health and Human Services launched a “Test to Treat” program, where patients who test positive for SARS-CoV-2 in a healthcare setting can then be given a prescription for Pfizer’s oral antiviral Paxlovid. Rapid tests are critical in this effort because treatment must be started within 5 days of symptom onset for it to be most effective.
But the rollout has been rocky. As part of the program, patients must test within a healthcare setting (even if it’s a rapid test), instead of being able to use a rapid test taken elsewhere. Monica Eng, a reporter with Axios Chicago, had already tested positive for SARS-CoV-2 on March 25, but had to get tested at a pharmacy listed on the Chicago Department of Public Health as a “Test to Treat” facility in order to get a Paxlovid prescription. The first 10 pharmacies she called said they’d never heard of the program or hadn’t started working within it yet.
For Test to Treat to really work, Mina said, people who test positive at home or work need easy access to treatment options rather than having to find a doctor’s office or pharmacy that can test them again and then make a recommendation. Ideally, these patients would be able to set up a telemedicine appointment to be evaluated and be prescribed the right treatment, whether that’s antiviral pills or monoclonal antibodies, he said.
Messaging About Rapid Tests
Clinical laboratorians can play a role in messaging about rapid antigen tests, both to healthcare practitioners on how best to use them, and to the general public. Many Americans relied on negative rapid tests to visit family during the December 2021 holidays, which coincided with the omicron surge, without understanding that a negative on this test wasn’t necessarily a green light to gather. Cases hit their U.S. peak in mid-January 2022.
“We can help create better messaging for the public, and stress that there is no perfect test,” said Lam. “There’s no such thing as 100% sensitivity and 100% specificity. Knowing that and trying to communicate that to the public is really important.”
That doesn’t mean bashing rapid tests, but educating the public on how to use them, and their limitations. At the time of this interview, Lam had just returned from a crowded conference where participants took a rapid test beforehand. “Even if we’re all negative, we should probably still wear masks and be wary of people who develop symptoms. That’s where you have to keep these imperfections in mind,” he said.
Karon added that it’s challenging enough to run the Mayo Clinic’s point of care testing program and communicate to healthcare workers the limitations of point-of-care tests. In the face of so much promotion around rapid tests to get people to use them, the communication challenge to the general public is enormous. “It’s a little like managing point-of-care testing for the whole country,” he said.
Clinical laboratorians can work with public health professionals, he said, to communicate both the limitations and importance of rapid tests while stressing the proper testing procedures. “I don’t know that it helps to say, ‘rapid antigen tests aren’t sensitive, don’t use them.’ That’s not taking public heath into consideration,” he said. “But we have challenges to overcome in terms of the testing and collecting process, and in proper interpretation of results. We need to be working together at the forefront on the use and value of rapid antigen tests.”
Jen A. Miller is a freelance journalist who lives in Audubon, New Jersey. +Twitter: @byJenAMiller