As the COVID-19 pandemic enters its fourth year, a negative result on a little plastic at-home test feels a bit less comforting than it once did.
Still, you dutifully swab your nostrils before dinner parties, wait 15 minutes for the all-clear and then text the host "negative!" before leaving your KN95 mask at home.
It feels like the right thing to do, right?
The virus has mutated and then mutated again, with the tests offering at least some sense of control as the Greek letters pile up. But some experts caution against putting too much faith in a negative result.
So it's only fitting to do a reality check on what those rapid COVID-19 tests, also called antigen tests, can do — and what they can't.
Is the latest omicron variant tripping up at-home tests?
For the most part, the answer is no.
That's because as the virus evolves, scientists are mainly seeing changes in its spike protein, which is what the virus uses to attack and enter healthy cells. But the rapid antigen tests aren't actually looking for that spike protein.
"[The tests] rely on detection of the nucleocapsid protein, which is the protein that is directly encapsulating the viral RNA," says Dr. Robin Colgrove, a professor at Harvard Medical School and chair of the Diagnostics Committee of the Infectious Diseases Society of America.
He says this interior protein really hasn't changed much as the virus has mutated over the years. So, at least for now, the rapid tests can detect it.
Federal health agencies are monitoring the situation in case that changes. The Food and Drug Administration is working with the National Institutes of Health to study just how well the at-home tests work as the virus continues to evolve.
So far, the agencies have identified only one test — the Luminostics Inc. Clip COVID Rapid Antigen Test — that has been rendered less reliable in the face of new variants. And even then, the FDA says "the impact does not appear to be significant."
Are antigen tests taking longer to show a positive?
Some people report having negative antigen test results for days, despite having a known COVID-19 exposure and the telltale symptoms. Eventually, they test positive, but it can sometimes take as long as a week.
The phenomenon is somewhat mysterious, says Colgrove. He acknowledges that doctors are seeing it, but so far, it's only anecdotal.
"What kind of an experiment would you have to do to answer that question?" he says, explaining that it would be difficult to study.
Many factors could make it seem as though home tests are taking longer to register a positive result, such as the virus multiplying faster somewhere other than the nostrils in some patients, says Dr. Geoffrey Baird, chair of the Department of Laboratory Medicine and Pathology at the University of Washington School of Medicine.
But Baird says perhaps the biggest factor is human error. After all, people doing these tests at home make mistakes and aren't trained like those who are doing COVID-19 tests in a lab.
"There's going to be some people who stick it in their mouth," he says, explaining that not everyone follows the testing instructions as written. Some people even get mucus on the swab, mistakenly thinking mucus will have plenty of virus in it. "Actually you don't want snot on the thing."
And while, on average, people will get a positive antigen test result around the time they become infectious, Baird says it's important to remember that there will always be plenty of people on either side of that average: those who test positive much earlier than most and those who test positive much later.
How well do these tests really work?
Antigen tests can be useful in certain situations (more on that in a minute), but Baird stresses that they have their limits. That was true even before the pandemic.
"Similar technology has existed for influenza for years and the recommendation was not to use them," he says.
Antigen tests look for specific proteins inside the virus. Users typically swab their nostrils, and the tests take about 15 minutes to render a positive or negative result. But these at-home tests need much more virus to generate a positive result than a PCR test, which is done in a lab and involves trace amounts of viral genetic material "amplifying" over time. Results usually take a day or so to come back. Even if very little virus is present, there should be enough to trigger a positive result (PCR tests may also keep turning up positive long after someone has cleared the infection).
Both kinds of tests have their advantages and disadvantages. And there are two measures of test performance to know about: specificity and sensitivity.
Specificity is how good the test is at avoiding false positives. And sensitivity is how good the test is at finding the virus.
According to the CDC, antigen and PCR tests are both good at avoiding false positives, but PCR tests are generally more sensitive than home tests. That means antigen tests aren't all that useful for ruling out COVID-19, but they can be valuable for confirming that cold really is COVID-19.
If you don't have any symptoms though, don't count on antigen tests to give you a definitive answer on whether or not you're in the clear. This is also what researchers found when they took a look at more than 100 studies of antigen tests and published their findings in the Cochrane Database of Systematic Reviews this past July.
"Rapid antigen tests are considerably less accurate when they are used in people with no signs or symptoms of infection, but do perform better in people who have been in contact with someone who has confirmed COVID‐19," they wrote.
The same researchers also found that not all home tests were equally accurate. Their review included 49 different kinds of tests.
"We saw a lot of variation in the sensitivity of different brands of tests and our overall results combine findings from different studies that evaluated the same tests," lead author Jacqueline Dinnes from the University of Birmingham said in a podcast about the report.
So what are these tests actually good for?
Even though it seems like a good idea to have everyone take a rapid COVID-19 test the day of a gathering to make sure they're negative, experts say that's not how the tests were meant to be used.
"A positive test is almost always true," Colgrove says. "So in a person with an exposure or a person with suggestive symptoms, if they do a test and it's positive, you're done. You have your diagnosis."
It's a slightly different story if you are getting over COVID-19 and are testing to see whether you're still positive.
But a negative "does not rule out" a COVID-19 infection, according to the Centers for Disease Control and Prevention. If someone tests negative, they're supposed to take another antigen test 48 hours later to see if it turns positive. And if that person has a known COVID exposure or symptoms, the FDA recommends a third test 48 hours after that.
The best way to use the tests is to know their limits and follow instructions for retesting when you get a negative result.
"In a person who had suggestive symptoms now, in the middle of the epidemic where the prevalence of the infection is high, a single negative test is not enough to rule out infection," Colgrove says.
If you have COVID-19 symptoms, even if your test is negative, it's a good idea to be cautious and just stay home.