How confident can you be in a coronavirus test?

Katherine J. Wu, The New York Times

Posted at Dec 24 2020 10:33 AM

How confident can you be in a coronavirus test? 1
A woman has a swab sample taken for a coronavirus disease (COVID-19) antigen test at a cultural center in the working class neighborhood of Vallecas in Madrid, Spain, October 1, 2020. Sergio Perez, Reuters/File

In mid-November, David Piegaro tested positive for the coronavirus. His results came too late.

The night before, Piegaro, a member of the National Guard, had driven to New Jersey to visit his family after receiving two negative rapid test results two days in a row. By the next morning, he was gone. But the single overnight stay was enough to spread the virus Piegaro was unknowingly carrying to multiple members of his family, including his grandfather, who ended up spending two weeks in the hospital.

“Those two negative results gave me more confidence than I should’ve had that I could see my grandfather,” Piegaro said.

Since the start of the pandemic, the US Food and Drug Administration has issued emergency green lights to more than 200 types of coronavirus tests, each with its own curiosities and quirks. Yet we tend to talk about all of them in the same binary way, with identical terms: positive, negative, true, false.

But when it comes to interpreting results, not all positives and negatives are equally reliable. Factors like whether you had symptoms, or the number of people in your neighborhood who are infected, can influence how confident you should be in your test results.

“It’s about context,” said Andrea Prinzi, a clinical microbiologist and diagnostics researcher at the University of Colorado Anschutz Graduate School. “Your test doesn’t end when you get your result.”

WHY 'POSITIVE' AND 'NEGATIVE' ARE MISLEADING 

Experts say these words imply a deceptive permanence. “Negative” can mislead people into thinking they are safer from the virus than they actually are.

Some people may mistakenly believe that testing negative gives them a free pass to socialize — “I got a negative test and now I can go visit grandma”– said Dr. Ashish Jha, the dean of the Brown University School of Public Health.

But certain types of tests, especially the rapid ones, aren’t reliable at picking up on low levels of the virus and might mislabel infected people as “negative.” And no test can capture a person’s status in the future. People who test negative one morning might be positive by the next, either simply because the test missed the virus, or because they were newly infected.

A “negative” may be better described as a given test’s inability to detect the virus at a single point in time: an empty freeze frame.

'NOT DETECTED' DOESN'T MEAN IT'S NOT THERE 

Many coronavirus test results already say “detected” or “not detected” as their default readout, a distinction that several experts call more useful.

“‘Not detected’ really points to the moment,” said Dr. Valerie Fitzhugh, a pathologist at Rutgers University. “It wasn’t detected today. That doesn’t mean I won’t have it tomorrow.”

Some tests, called molecular tests, look for the coronavirus’ genetic material, or RNA. (Whether done by a nose swab or saliva, these tests are generally considered to be reliable, especially if processed in a lab with a technique called polymerase chain reaction, or PCR.) Others, called antigen tests, hunt instead for pieces of coronavirus proteins, or antigens. 

Antigen tests tend to be faster, but are worse than molecular tests at identifying coronavirus cases, especially when the virus is present at relatively low levels, making it possible for someone to be RNA “positive,” but antigen “negative.”

This may occur because the virus is on its way out of the body, or because it has largely failed to gain a foothold. But it’s also possible that antigen tests might not identify the virus on its upswing, in the early days of infection.

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WHY THE 'WHY' OF TESTING MATTERS 

No test is perfect. But the likelihood of a false positive or a false negative can vary drastically depending on the circumstances under which a test was taken. The two most important of these are people’s recent health history, and how much the virus has spread in their community. Scientists call the confluence of these factors pretest probability.

If a person recently started feeling sick with COVID-like symptoms or interacted with someone infected, there is already good reason to suspect the virus is present.

People in this category who test positive can usually be pretty confident in a positive or “detected” result, said Dr. Benjamin Mazer, a pathologist at Johns Hopkins University. They sought out the test with the idea that something was likely to be amiss — like dusting for fingerprints at the scene of a crime that’s already occurred.

In such a situation, a “not detected” result might seem more suspicious, and warrant a retest, especially in an area where the virus has been running rampant.

The opposite is true of a screening test — a routine check for the healthy and symptomless. Pretty much anyone can opt for a screen, introducing more noise into the search for the virus. It’s more like hunting for a felon before any wrongdoing has occurred. That means more errors will inevitably crop up.

With screening, “you’ll need to be more cautious with your result,” said Prinzi of the University of Colorado. Healthy people with no known exposures who live where the virus is scarce are pretty unlikely to test positive. If they do, FDA guidelines say that these people might want to confirm the positive result with another test, especially if the original was an antigen test, which tends to produce more false positives. (In the meantime, it’s still a good idea to self-isolate.)

In regions where coronavirus cases are rare, false positives could outnumber true positives — a situation that could cause undue harm and erode trust in testing. These errors will also go up when a less accurate test is used.

TEST AND INTERPRET WISELY 

Now that fully at-home rapid tests are trickling into the market, Americans may need to confront these testing conundrums regularly. Two of the three home tests cleared by the FDA to date are antigen tests; one of those requires a prescription and is intended for use only in people with symptoms. A third is a prescription-only molecular test, made by Lucira Health.

Whether you receive your result at a testing site or in your living room, think about how you’ve been feeling and where you’ve been. If there’s reason to think your test should detect the virus, such as symptoms, a recent exposure or a current outbreak in your community, a positive result is probably correct. That probability increases if the test you’re using has a reputation of being very accurate, such as a laboratory test.

A surprise positive shouldn’t be dismissed, though, especially as the number of coronavirus cases continues to balloon — increasing the pretest probability for millions of people nationwide.

© The New York Times Company

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