In mid-June, Joanna Dreifus hit a pandemic milestone. The final member of her household—her teenage son—reached the point of full vaccination. “We had about two weeks where I thought, Phew, we’re okay,” Dreifus, a special-needs-education consultant in New York City, told me. Then the Delta variant took over. By July Fourth weekend, murmurs of post-vaccination infections, though uncommon, were starting to trickle into her social-media feeds. “I knew I’d need to stock up on more tests,” Dreifus said.
She estimates that she’s now using at-home antigen tests—the over-the-counter ones that return results in minutes—to screen her family for the coronavirus about three times a month. She pulls them out when anyone feels a sniffle coming on, or when she and her kids, 15 and 18, are about to visit her elderly, vaccinated parents. Dreifus knows the vaccines are still doing their part, but “Delta has basically taken us back to many of our pre-vaccination precautions,” she told me. Combined with masking, distancing, and socializing mostly outdoors, tests bring her extra peace of mind.
Dreifus’s decision turned out to be prescient. In early July, the CDC was still insisting that fully vaccinated people didn’t need to mask indoors, or seek out tests after virus exposures if they didn’t have symptoms—guidelines that hinged on the assumption that vaccinated people were almost never getting infected. By month’s end, spurred by Delta’s rise, the agency rolled those recommendations back. Vaccines clearly still curb a person’s chances of catching the coronavirus and passing it on. But they can’t stave off those outcomes completely, especially in the parts of the United States where the super-transmissible variant is running rampant. Right now, that’s just about everywhere.
As infections skyrocket, many Americans, like Dreifus, are clamoring once again for tests. Over-the-counter, at-home tests in particular have been flying off pharmacy shelves and out of online inventories, as companies scramble to scale up demand. People are turning to these tests when they feel sick, to avoid an onerous trip to a testing site or a doctor’s office or the days-long wait that tends to come with laboratory-based tests. At-home tests are also being heavily marketed as an option for folks who feel healthy to screen themselves before they venture out into the world. At an extreme, rapid tests have even become bouncers for big events—sports games, weddings, concerts, clubs—whereby negatives sometimes green-light people to enter packed indoor settings, or even strip off their mask. “I still see people throwing parties and testing people as they come in at the door,” Omai Garner, a clinical microbiologist and diagnostics expert at UCLA, told me.
But that, Garner and other experts say, is exactly the wrong approach. Tests have never completely ruled out that someone is infected or infectious, which means they don’t work as one-off tickets to freedom, carte blanche to ditch other public-health recommendations. Delta has made blasé approaches to testing all the more precarious. And with the world only partly vaccinated, interpreting test results has gotten trickier as well.
Coronavirus testing is in a much different place than it was a year ago. Thanks to the rise of at-home diagnostics, people with means and access no longer have to tangle with the backlogged laboratory testing that plagued the country earlier in the pandemic. Dozens of FDA-authorized tests now include a home-collection option; although some need to be shipped out for processing, require a prescription, or call for telehealth supervision, others are available over the counter and can run from start to finish at home, no proctor necessary. “It’s about availability and ease of use,” says Benedicte Callan, a health-policy researcher in New Jersey, who’s been regularly buying a popular at-home version of an antigen test called the BinaxNOW, made by Abbott Laboratories, for her family. The credit-card-size contraption runs at roughly $25 for a pair of shallow-nose-swab tests, and can return a result in about 15 minutes.
These tests are helping to fill a big diagnostic chasm. Last winter and spring, as health departments pivoted their resources to vaccines, many mass testing sites closed, and surveillance efforts petered out. Demand for tests plummeted so sharply that Abbott reportedly instructed factory workers to destroy their inventory earlier this summer, depleting their stocks just before demand skyrocketed again. (Abbott subsequently published a rebuttal to The New York Times’ report.) Now, with Delta blazing, turnaround times for laboratory tests have ballooned into several-day waits—potentially too late to stop an outbreak.
Researchers have long known that rapid antigen tests, although convenient, sacrifice some accuracy for their art. Compared with PCR-based laboratory tests, they’re not very good at rooting out the coronavirus when it’s present in low amounts. Whereas PCR testing involves repeatedly xeroxing SARS-CoV-2’s genetic material, so that it can be detected even when it’s exceedingly scarce, antigen tests just scan for what’s already floating around—a coarser kind of survey. (A different type of rapid test pantomimes the PCR’s process and is thus more accurate, but some models can cost two or three times more, and are often sold out.)
Garner says the tests will work best for people who already feel ill. “If you’ve got a kid and they come home with a fever, that’s a good way to use it,” he told me. Trials run by test makers show that when antigen tests are taken in the first few days after someone’s symptoms start, their results can match up with those of PCR tests more than 80 percent of the time, though data collected by independent research groups have often produced slightly less stellar results. When antigen tests are used in people who feel healthy, however, their performance tends to take a nosedive. Studies have found that some of the tests might catch fewer than half of the symptomless infections identified by PCR. The people the tests miss might be recently infected, for instance, and incubating the virus at low levels before it truly takes off. They can still be contagious. “Literally all that tells you is, at that minute, you didn’t have a ton of virus,” Garner told me. (False positives, too, can become a concern, but they’re less of an issue when case rates are high, as they are now.)
Some accuracy issues can be averted by taking these tests several times a week, if people can find and afford them. Low-level infections that are missed one day could be caught the next. And at the community level, some researchers have argued, widespread, frequent testing could help identify many of the people who are harboring the most virus, and are potentially most poised to spread it—a sort of quantity patch for the tests’ quality flaws. Repeat testing is what the FDA now recommends for people using over-the-counter tests as asymptomatic screens. The two-pack BinaxNOW tests, for instance, are meant to be taken fewer than three days apart; some models advocate that rapid tests be taken almost daily. “It’s clear that testing, particularly rapid testing, will be needed to manage this next phase of the pandemic,” John Koval, Abbott’s director of public affairs for rapid diagnostics, told me.
But often, that’s not how people rely on rapid tests. “Using these one-off, for one event, is not watertight,” Alison Buttenheim, a behavioral scientist at the University of Pennsylvania who studies vaccines, told me. Negatives—even a pair of them—can’t guarantee that the virus wasn’t there, just that it wasn’t measured. And tests can’t predict the future if they’re taken days in advance of an event. Delta has a penchant for building to high levels in the airway, which does likely make it easy to detect, but it accumulates fast, so it might leave open only a small opportunity to pinpoint the virus before it hops into someone else. “It’s a tighter, earlier window,” Susan Butler-Wu, a clinical microbiologist at the University of Southern California, told me. Federal documentation for most rapid tests still calls negative results “presumptive,” noting that sometimes, it’s a good idea to confirm with a laboratory test.
Vaccination complicates all of this further. An infection that takes root in an immunized person simply won’t look the same as it does in someone who’s never seen the virus before; with shot-trained immune cells at the ready, the pathogen will get stamped out faster. Researchers are still figuring out how commonly, and for how long, vaccinated people may be contagious. For them, positive results could merely be an indication of debris from the virus, after immune cells have defeated it—junk that doesn’t actually pose a transmission threat. Sometimes, a symptomless positive is just “your vaccinated body doing the exact thing it’s supposed to do,” Jennifer Nuzzo, the lead epidemiologist for the COVID-19 Testing Insights Initiative at the Johns Hopkins Coronavirus Resource Center, told me. Until we know more, positive test results should still send people into isolation. But vaccines might lower the likelihood that positives are infectiously meaningful.
None of this should imply that vaccines have made tests obsolete. Rather, testing etiquette is getting rewritten, as the virus continues to shape-shift and the nature of infections change. Having testing available, in any form, certainly offers more protection than not. But navigating all the uncertainties of life with Delta—and any variants beyond—demands reckoning again with the limitations of tests, and squaring them with the current pandemic moment.
Interpreting a test result isn’t just about checking a cartridge for a colored line, or the words positive or negative. If you have symptoms, live in a high-transmission county, or had a recent exposure to a known COVID-19 case, you have a higher so-called pre-test probability and can have good confidence in a result that says the virus is there. But the converse of that is also true: Negatives might not actually be negatives if they seem like they shouldn’t be. When in doubt, Butler-Wu recommends considering the goal of testing and setting expectations accordingly. Or, as she said a colleague once rather vividly described it to her: “Doing a test is like picking your nose. Don’t do it unless you have a plan for what to do with what you find.” At best, a test can stop you from heading out the door with a burgeoning infection. At worst, it could mistakenly embolden someone to take an unnecessary risk. “You have to consider: What’s the cost of being wrong?” Buttenheim told me. Tests sample individuals, but their results affect entire communities.
That makes it all the more troubling that self-testing has become so socioeconomically stratified. Most tests’ current prices—and woefully inadequate availability—make them unaffordable to many Americans, including some of the same communities that already lack access to mass testing sites. (Weekly two-packs of the BinaxNOW for a family of four would run up a monthly bill of about $400.) The global portrait for at-home testing looks even worse; many other countries haven’t had the supply or infrastructure necessary to roll out at-home tests, says Neha Agarwal, who leads the PATH Diagnostics Program, a nonprofit that’s been tracking coronavirus tests. A lot of over-the-counter tests also don’t require people to report their results, potentially stymieing efforts to track whom the virus is infecting, and forecast where it might head next.
As we approach two years of facing off against this virus, many of us, as hosts, are different now: more knowledgeable and, thanks to vaccines, far better defended. We have more and better tests. But like everything else in our pandemic toolkit, tests will fail when they’re asked to bear the prevention burden alone.
Author: Amaury Abreu
