For a recent flight that required a negative COVID-19 test result, I went through a process so silly and laborious that it got me wondering. First, I booked an appointment at an approved testing center, about a 25-minute drive from my home. Upon arriving, I paid $175 to take a polymerase chain reaction (PCR) test. I then drove home, downloaded an app and waited 24 hours—all to receive results that, in many other countries, can be obtained in a fraction of the time without ever leaving the house.
So why, more than a year into a pandemic, does the U.S. lag behind other developed nations in the deployment of rapid antigen testing? Recently, for the first time, we received a hint that our nation’s top health officials have been wondering the same thing.
On March 31 the Food and Drug Administration effectively made a game-changing announcement: two rapid at-home antigen tests, Abbott’s BinaxNOW and Quidel’s QuickVue, will soon be sold over the counter (OTC) on drugstore shelves, without the need for a prescription.
That may sound like a little. It’s a lot. It is of such critical potential impact, in fact, that Harvard University epidemiologist Michael Mina—who has for months been a vocal advocate of rapid antigen testing for screening purposes for months—proclaimed in an April 1 media call that March 31 “was a massively important day … on the testing front.”
There’s no prescription needed. You can self-administer the test at home—or, depending upon the need, at schools, workplaces and community centers, for example—so that you and the people around you can know almost immediately whether it’s safe to congregate. Because the virus that causes COVID-19, SARS-CoV-2, and its variants can spread asymptomatically, experts believe these tests could help detect them early, while people may be vectors of infection, and thus break the chain of transmission.
“Had we had these tests in a widely scalable at-home, simple to use fashion last summer, we could have prevented hundreds of thousands of deaths. We could have prevented surges of cases,” Mina said in the April 1 press conference. This pandemic “is still a massive tragedy every single day. And if we can use these types of tests to mitigate spread moving forward … that alone might be enough to ensure that outbreaks don't grow.”
This is clearly a shared view that is acted upon in other countries. Switzerland’s Federal Council recently announced it is “massively expanding” its rapid testing system with "free tests for all." As of March 8, everyone in Germany can receive rapid antigen testing once a week for free at a screening center or pharmacy, according to Sandra Ciesek, director of the Institute of Medical Virology at University Hospital Frankfurt in Germany. The Federal Council aims to increase this to five free self-tests per person a month as better tests become available. "To ensure that everyone can be tested immediately, all tests in pharmacies and test centres will be free of charge, even for people without symptoms,” the council wrote in a news release.
And in January, England committed to scaling up its rapid testing program. By March, free testing for all businesses was offered, and as of April 9th, twice-a-week free testing is available to everyone in the country. Regular workplace testing is a vital part of our route back to normal life,” said U.K. health secretary Matt Hancock in a March statement. “These rapid tests will [allow] positive cases of COVID-19 to be caught quickly, which is crucial in helping businesses protect their workplaces and employees as we cautiously lift restrictions.”
In the U.S., by comparison, things moved at an agonizingly sludgy pace. An FDA official told me the agency cannot compel manufacturers to submit applications for specific tests. Rather the developers decide for themselves whether to apply for a test that will be prescription or over-the-counter. Prior to the FDA’s statement March 31, of the 16 rapid antigen tests that had been approved, only one was greenlit for home over-the-counter use (without a prescription) by Ellume, and it is not yet available to the public for purchase. That is about to change dramatically.
The newly approved tests are authorized by the FDA for serial use, meaning an individual could be tested now and then again within 24 to 36 hours. Serial testing is important because it can improve the sensitivity of the test. If you’re in the early phase of infection, when viral levels are low, a test’s result may be a false negative—that is, it might show negative when, in fact, you’re positive for COVID. A test repeated the next day would more likely be positive, due to rapid increases in viral levels during the acute stage.
Mina and others hope that Americans will soon use these tests in the morning. Brush your teeth, take a quick 30-second test (it’s similar to a pregnancy test), come back in 10 to 15 minutes to check the results and, if clear, head to school or work. If you’re positive, do a more accurate nucleic acid amplification test (such as a PCR test) to be sure and then self-isolate.
Mina has pushed hard for the approval of these less expensive, simpler antigen tests for several reasons. One is simply scale. Manufacturers can ramp up production to tens of millions of tests per day, according to Mina—an amount that would be necessary if much of the population is using these assays. With Abbott’s BinaxNOW manufacturing facilities able to produce tens of millions of test per month and Quidel’s goal of 50 million of its QuickVue tests per month by the end of 2021, according to company spokespersons, Mina is hoping more companies will enter the space so availability in the near term does not become a big issue.
In a March 31 press release, Abbott said its test should be available nationally in “large quantities" at major food, drug and mass merchandiser retailers—and it has said they will be sold to retailers at a cost that will be in the “single digits.” A Quidel spokesperson wrote in an email exchange that the company will soon announce pricing on its two-test unit carton.
The need remains high for a continued buildup of fast, accessible testing, particularly for screening. ”We are in a risky period with variant growth, incomplete vaccination, return to school, increased population mobility and reduced mask wearing,” says Bruce Tromberg, director of the National Institute of Biomedical Imaging and Bioengineering at the National Institutes of Health in an interview. “The need to do screening, using accessible tests at home, on a large scale and on a regular cadence, is even more important.”
PCR tests have been recognized as the gold standard to diagnose acute infection with SARS-CoV-2 because of their high sensitivity—but they often require a central lab for processing and many cannot be done quickly, and delays in reporting the results increase the chance that someone is spreading the virus while waiting to hear back on their test. While not every PCR test costs the $175 that I paid (the Centers for Disease Control and Prevention (CDC) website estimates an average price of $75 to $100), its higher cost means that lower-income Americans will be less likely to be able afford it. Easier access to testing for these communities, which have shouldered much of the burden of COVID-19 and are facing health inequities, is welcome.
How accurate are these tests? The scientific community has debated the performance of rapid antigen tests. Officials at the CDC, along with most experts, believe antigen tests are less sensitive than PCR tests. In the April press conference, however, Mina contended that while PCR is the standard for diagnostic tests, it is “horribly not specific” for knowing who needs to isolate. He said it detected far too many remnants of viral RNA a week to two weeks, or more, after someone has become infectious. “This is not a public health test,” he said. “You can’t take a test that’s meant to be specific to the infectious period and make a gold standard against it that is totally not specific to the infectious period.”
In contrast, Mina believes rapid antigen tests have “excellent contagiousness sensitivity” (more than 98 percent sensitive) and that they're good at detecting people who have COVID during the period when they are most infectious and capable of transmitting virus to others. At this point, viral titers are high, and “the rapid tests will be positive,” Mina says. “When viral levels fall, the tests turn negative.” The Infectious Disease Society of America’s Website states, “Rapid tests may ultimately contribute to better SARS-CoV-2 containment via more efficient detection and subsequent isolation,” but it makes “no recommendations for or against using rapid tests.”
Where more experts do agree, and the CDC and FDA concur, is that rapid antigen tests, when performed serially, may increase the chances of detecting individuals who might be missed early with a single test. In a recent press release, Quidel indicated the test “shows excellent performance, with positive results agreeing with PCR 83.5 % of the time, and negative results agreeing 99.2% of the time.” A spokesperson at Abbott says BinaxNOW’s overall performance demonstrates 84.6 percent sensitivity and 98.5 percent specificity in people at seven days or less post-symptom onset at all Ct (cycle threshold) counts.
(If you’re curious as to whether these tests will detect the new variants, many experts believe they will. Mina explained at the press conference that they are unlikely to lose their effectiveness because the virus is mutating at a different part than the proteins these rapid tests are targeting.)
Approval of these tests comes on the heels of the FDA’s recent announcement of a streamlined pathway to emergency use authorization (EUA) for at-home screening tests, which allows companies to take already authorized prescription-based tests and apply to sell an over-the-counter claim without completing large trials. This appears to be working now with several over-the-counter tests approved.
In an interview, an FDA spokesperson said that based on more positive data related to serial testing that demonstrates good performance, a developer could potentially get an EUA approval for less sensitive tests, and be able to submit data post authorization. They indicated too that they do not hold any of the point-of-care tests or at-home tests to near the same high threshold as lab-based PCR test. In a press release, Jeff Shuren, M.D., J.D., director of the FDA’s Center for Devices and Radiological Health said, “As we've said all along, if it’s a good test, we’ll authorize it.”
Both the Biden administration and the CDC have indicated support for rapid testing. In February, President Joe Biden’s team announced that it would contribute $230 million to increase production of the Ellume antigen tests—the only OTC product on the market at the time authorized for both symptomatic and asymptomatic use. The company is expected to supply the U.S. with approximately 100,000 tests per month through July (and a total of 8.5 million guaranteed to the U.S. government), which is a start. Andy Slavitt, senior adviser for COVID-19 response at the White House, told reporters, “That’s good, but it’s obviously not where we will need to be.”
The CDC recently issued extensive new guidance related to the use of screening tests for COVID-19. In collaboration with the NIH, the agency announced a new public health initiative on March 31. The “Say Yes! COVID Test” initiative will enable 160,000 residents across two communities to perform free, rapid antigen tests three times a week for a month. “The new initiative is exciting,” Tromberg says. “It’s a real-world demonstration of how rapid-accessible tests can be used to stop the chain of transmission and reduce prevalence.”
This is our future, and it’s one way to help open our country. “Reliable and widely available testing is a critical part of our efforts to stop the spread of COVID-19,” said CDC director Rochelle Walensky in a recent statement. Abbott CEO Robert Ford took it a step further in the company’s March 31 press release, saying, "Together with vaccines, the BinaxNOW Self Test will help Americans get back to doing what they want and need to do—like going to work and school or seeing friends and family—with greater confidence."
It’s the kind of development Mina has been lobbying for during the better part of a year. Now, he said in the April 1 press conference, the FDA, CDC, NIH and White House “are all sort of simultaneously recognizing this is a very powerful tool over the last two, two and a half weeks…. I think that we should consider this sort of a pivotal change in the … testing landscape in the U.S.”
In Germany, meanwhile, the famed Berliner Ensemble theater has reopened to sold-out audiences. To attend the show, visitors must wear masks, social distance and present not only their tickets but a negative COVID result from a rapid test taken just 12 hours prior to showtime. It’s working quite well. Very soon, Americans, too, may be able to make their own curtain call.
This is an opinion and analysis article.