How Is COVID Testing Still This Confusing? – The Atlantic

Updated at 12:44 p.m. ET on November, 23 2021

In a world with perfect coronavirus tests, people could swab their nose or spit in a tube and get near-instant answers about their SARS-CoV-2 status. The products would be free, fast, and completely reliable. Positives would immediately shuttle people out of public spaces and, if needed, into treatment; negatives could green-light entry into every store, school, and office, and spring people out of isolation with no second thought. Tests would guarantee whether someone is contagious, or merely infected, or neither. And that status would hold true until each person had the chance to test again.

Unfortunately, that is not the reality we live innor will it ever be. No such test exists, K. C. Coffey, an infectious-disease physician and diagnostics expert at the University of Maryland School of Medicine, told me. Not for this virus, and not for any disease that I know of. And almost two years into this pandemic, imperfection isnt the only testing problem we have. For many Americans, testing remains inaccessible, unaffordable, and stillstill!ridiculously confusing.

Contradictory results, for instance, are an all-too-common conundrum. Cole Shacochis Edwards, a nurse in Maryland, discovered at the end of August that her daughter, Alden, had been exposed to the virus while masked at volleyball practice. Shacochis Edwards rapid-tested her family of four at home, while the high school ran a laboratory PCR on Alden. One week, 11 rapid antigen tests, 3 PCRs, and $125 later, their household was knee-deep in a baffling array of clashing results: Alden tested negative, then positive, then negative again, then positive again, then negative again; her father tested negative, then positive, then positive, then negative; Shacochis Edwards, who tested three times, and her son, who tested twice, stayed negative throughout. None of it was clear, she told me. Months after their testing saga, Shacochis Edwards is pretty sure the positives were wrongbut theres simply no way to know for sure.

Some conflicting results are just annoying. Others, though, can be a big problem when people misguidedly act on themunknowingly sparking outbreaks, derailing treatment, and squandering time and resources. And the confusion doesnt stop there. The tests come in an absurd number of flavors and packages, with subtle differences between brands. Theyre deployed in a disorienting variety of settings: doctors offices, community testing sites, apartment living rooms, and more. Theyre being asked to serve several very different purposes, including diagnosis of sick patients and screening of people who feel totally symptom-free.

Our tests are imperfectthats not going to change. The trick, then, is learning to deal with their limitations; to rely on them, but also not ask too much.

Tests are virus hunters. The best ones are able to accomplish two things: accurately pinpointing the pathogen in a person whos definitely infecteda metric called sensitivityand ruling out its existence in someone whos definitely not, or specificity. Tests with great sensitivity will almost never mistake an infected person for a virus-free onea false negative. High specificity, meanwhile, means reliably skirting false positives.

Our tests accomplish this in two broad ways. They search for specific snippets of the viruss genetic material, putting them in the category of molecular tests, or find hunks of pathogen protein, which is the job of antigen tests. (Most of the rapid tests you can find in stores are antigen, while PCR tests are molecular.) Both types will make mistakes, but whereas molecular tests repeatedly copy viral genetic material until its detectable, making it easier to root out the pathogen when its quite scarce, antigen tests just survey samples for SARS-CoV-2 proteins that are already there. That means theyre likelier to miss infections, especially in people with no symptoms.

Even super-sensitive, super-specific tests can spit out more errors when theyre mishandled, or when people swab themselves sloppily. That can be pretty easy to do when instructions differ so much among brands, as they do for rapid antigen tests. (Wait 24 hours between tests! No, 36! Swivel it in your nose four times! No, five! Dip a strip in liquid! No, drop the liquid into a plastic strip! Wait 10 minutes for your result! No, 15!)

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Random substances can also dupe certain tests: Soda, fruit juice, ketchup, and a bunch of other household liquids have produced rapid-antigen false positives, an oopsie that some kids in the United Kingdom have apparently been gleefully exploiting to recuse themselves from school. Manufacturing snafus can also trigger false positives, as recently happened with Ellume, a company that sells rapid antigen tests and had to recall some 2 million of them in the United States. (Sean Parsons, Ellumes CEO, told me that the issue is now under control and that his company is already producing and shipping new product to the U.S.)

Even when theyre perfectly deployed, tests can detect bits of the virus only at the moment a sample is taken. Testing negative for the virus isnt some sort of permanent identity; it doesnt even guarantee that the pathogen isnt there. Viruses are always multiplying, and a test that cant find the virus in someones nose in the morning might pick it up come afternoon. People can also contract the virus between the tests they take, making a negative, then a positive, another totally plausible scenario. That means a test thats taken two days before a Thanksgiving gathering wont have any bearing on a persons status during the event itself. People want tests to be prospective, Gigi Kwik Gronvall, a senior scholar at the Johns Hopkins Center for Health Security, told me. None are.

Recently, I asked more than two dozen peopleco-workers, family members, experts, strangers on Twitterwhat they envisioned the perfect coronavirus test to be. The answers I got were all over the place.

People wanted tests that were cheap and accessible (which theyre currently not), ideally something that could give them a lightning-fast answer at home. They also, unsurprisingly, wanted totally accurate results. But what they wanted those results to accomplish differed immensely. Some said theyd test only if they were feeling unwell, while others were way more interested in using the tests as routine checks in the absence of symptoms or exposures, a tactic called screening, to reassure them that they werent infectious to others.

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At least for now, certain tests will be better suited to some situations than others. The best test to use depends on the question youre asking of it, Coffey told me. When someones sick or getting admitted into a hospital, for instance, health-care workers will generally reach first for the most precise, sensitive test they can get their hands on. A missed infection here is high-stakes: Someone could be excluded from a sorely needed treatment, or put other people at risk. But lab tests are inconvenient for the people who take them, and very often slow. Samples have to be collected by a professional, then sent out for processing; people can be left waiting for several days, during which their infection status might have changed.

Using a rapid test can be much more convenient, especially if people feel unwell at homeand these tests do work great for that. But things get hairier when these products are used for screening purposes. Asymptomatic infections are a lot harder to detect in general, because theres no obvious bodily signal to prompt a test. Youre essentially randomly sampling, which means more errors will inevitably crop up, Linoj Samuel, a clinical microbiologist at the Henry Ford Health System in Michigan, told me. To patch this problem, the FDA has green-lit several rapid tests that tell users to administer them seriallyat least once every couple of days. A test that misses the virus one day will hopefully catch it the next, especially if levels are rising.

But for those hoping to narrow in on the people who are carrying the most virus in their airwayand probably pose the biggest contagious risk to othersrapid antigen tests might be enough to do the trick precisely because they are less sensitive. They wont catch all infections, but not all infections are infectious; a positive antigen result, at least, could be a decent indication that someone should stay home, even if theyre feeling perfectly fine. That logic isnt airtight, though. Antigen-positive is not precisely synonymous with infectious; antigen negatives cannot guarantee that someone is not. For SARS-CoV-2, we dont know the thresholdhow much virus you need to be carrying to be contagious, Melissa B. Miller, a clinical microbiologist at the University of North Carolina at Chapel Hill, told me. People on the border of positivity, for instance, might still transmit.

People are turning to testing for asymptomatic check-ins that can give them peace of mind before a big event, or even give them the go-ahead to travel overseas. But a lot of these screening tests were initially designed to diagnose people who were already sickand the tests performance wont necessarily hold when theyre being repeatedly used on symptom-free people at home.

Part of the problem can be traced back to how the United States thinking on testing has evolved. Early on in the pandemic, regulatory agencies like the FDA prioritized tests for symptomatic patients; the agency has since noticeably shifted its stance, authorizing dozens of tests that can now be taken at home. But there are still some relics that have influenced how the tests have, and have not, been evaluated for use.

Tests such as the Abbott BinaxNOW, for example, were first studied as a rapid diagnostic that people could take shortly after their symptoms first appeared. It can now be used as a screener, when it is serially administered at home to asymptomatic people (which is why the tests are sold in packs of two). But to nab that expanded authorization from the FDA, the company didnt have to submit any data on the tests performance when it was serially administered at home, or how well it worked in asymptomatic people. Instead, the FDA has been green-lighting serial tests based on how well their results match up to PCR results in symptomatic people. They just have to detect 80 percent of the infections that the super-sensitive molecular tests do, in a clinical setting.

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I asked the FDA why that was. The FDA does not feel that requiring specific serial-testing data from each manufacturer is necessary due to the current state of knowledge on serial testing, James McKinney, a spokesperson, told me. (Some companies that already have products for sale, including Abbott and Becton, Dickinson, are collecting additional data now under FDA advisement.)

The repurposing of tests feels a little weird, experts told me. I dont see how you can reuse the same data, for very different goals, Jorge Caballero, a co-founder of Coders Against COVID, whos been tracking coronavirus-test availability and performance, told me. That doesnt mean these tests are useless if you dont have symptoms. But without more evidence, were still determining exactly what theyre able to tell us when we self-administer them once, twice, or more, even as were feeling fine.

The results produced by a coronavirus test arent actually the end of the testing pipeline. Next comes interpretation, and thats a nest of confusions in its own right. Sure, tests can be wrong, but the likelihood that they are wrong changes depending on whos using them, how, and when. People dont always talk about what to do when theyre shocked by a resultbut that sense of surprise can sometimes be the first sign that the tests intel is wrong. People should have some confidence on how likely it is they have the disease when they test, Coffey told me. Ideally, the test should confirm what you already think.

Consider, for example, an unvaccinated person who starts feeling sniffly and feverish five days after mingling unmasked with a bunch of people at a party, several of whom tested positive the next day. That persons likelihood of having the virus is pretty high; if they test positive, they can be pretty sure thats right. Random screenings of healthy, vaccinated people with no symptoms and no known exposures, meanwhile, are way more likely to be negative, and positives here should raise at least a few more eyebrows. Some will be correct, but truly weird results such as these may warrant a re-check with a more accurate test.

Yet another wrinkle has become particularly relevant as more and more people get vaccinated. Tests, which look only for pieces of pathogens, cant distinguish between actively replicating virus that poses an actual transmission threat, and harmless hunks of virus left behind by immune cells that have obliterated the threat. A positive test for a vaccinated person might not mean exactly the same thing it does in someone who hasnt yet had a shotmaybe, positive for positive, theyre less contagious. Thats not to say that noninfectious infections arent still important to track. But positives and negatives always have to be framed in context: when and why theyre being taken, and also by whom.

Tests will have to be part of our future, for as long as this virus is with us. But understanding their drawbacks is just as essential as celebrating their perks. Unlike masks and vaccines, which can proactively stop sickness, tests are by default reactive, catching only infections that have already begun. In and of themselves, they dont stop transmission, Coffey told me. Its about what you do with the test. If you dont do anything with the result, the test did nothing.

This article previously misstated the type of coronavirus test manufactured by the company Ellume.

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How Is COVID Testing Still This Confusing? - The Atlantic