Take Negative COVID-19 Tests Seriously, But Not Literally

Kayleigh McEnany tested negative for COVID-19 last Thursday. She tested negative again on Friday. And on Saturday. And also on Sunday.

But she wasn’t negative on Monday.

And that presents a quandary even if you’re not the White House press secretary. What if you get tested because someone close to you tested positive, but your test shows you’re negative … yet three days later you aren’t, and, unlike McEnany, you have no idea you have COVID-19 because you don’t get tested daily?

The recent outbreak among White House staff and other Republican officials can provide some insight on how to make ourselves, and our communities, safer. That’s because, experts told me, sometimes a “negative” test result isn’t just a negative test result. Sometimes it’s just the first stop on the way to testing positive.

Those first few McEnany tests fall into the category of “false negatives,” said Bobbi Pritt, a microbiologist at the Mayo Clinic. She was infected, but the tests couldn’t tell that yet. Nobody knows exactly how common false negatives are, said Steven Woloshin, co-director of the Center for Medicine and Media at The Dartmouth Institute, but they aren’t rare. In one study from China, between 11 and 40 percent of tests1 conducted on 213 hospitalized, COVID-positive patients in the first seven days of illness came back negative. Another paper, this one a review of 34 studies accounting for more than 12,000 patients, suggested a false negative rate between 2 and 58 percent.

There are multiple reasons why a test could produce a false negative. In McEnany’s case, it’s likely because there’s a lag time between when someone gets an infectious dose of the SARS-COV-2 virus and when there is actually enough virus in their body to register on a test. “Say somebody gets exposed today, then half the people will start having positive test results in five days,” said Davey Smith, a translational research virologist at the University of California San Diego. “Eighty percent will have it by [day] 10 and virtually everyone would have it by 14.”

People who know they’ve been exposed to COVID-19 often want to come in right away and get a test, Smith said. But that’s the opposite of what you need to do. In order to test positive, you have to have enough virus in your system for the test to spot its genetic material in your sample. But virus replication takes time. If you’re tested on day four, there’s a greater than 50 percent chance that any negative test result is untrustworthy.

But it gets more complicated than that. Testing too soon is a concern for anyone, but if you’re one of the people who contracts COVID-19 and isn’t having a serious case, there’s also such a thing as testing too late, Pritt said. In mild cases, she told me, concentrations of virus in a person’s system can start to decline six days after infection — meaning if you got tested after that, the result might come back negative and people who have been in contact with you might not know they were ever at risk.

You can still test positive in the first week after infection — and serious cases can test positive for far longer — but the window for when everyone is most likely to get a “negative” that truly means negative is small. There’s a reason state health departments are recommending that asymptomatic people who think they’re at risk of COVID-19 be tested five to seven days after exposure. What’s more, Woloshin said, the tests only tell you if you have the virus — not whether or when you are contagious. It all leaves a lot of room for error.

This isn’t anything unique to COVID-19. With any virus, there will be differences in how long it takes to replicate to detectable levels. Some are fast. Some, like HIV for example, can take months. And how long it takes a respiratory virus like COVID to reach a detectable point can vary based on the strain of the virus, the person’s immune system, how much virus they inhaled to begin with, and other factors. “If I get a bunch of virus at once, the amount of time it takes to replicate enough to come out my nose is shorter,” Smith said.

But there are two other reasons why false negatives happen, Pritt told me. First, the test might not have reached the parts of your body where the virus concentrates. “The gold standard is still the nasal pharynx, several inches up your nose. The amount of virus is higher there than in the tip,” she said.

Then, there’s also errors in the tests themselves. No test is perfect, after all. And different tests have different profiles of how likely they are to fail. For example, PCR tests — the ones that the virus’ genetic traces in samples taken from deep in your nose — have been kind of the workhorse of diagnostic testing throughout the pandemic. There are different kinds, but generally, experts said, they all have what is called high sensitivity — that is, if you take them at the right time, they’re pretty unlikely to mess up in ways that result in false negatives. The newer rapid tests, on the other hand, are kind of the opposite. They might turn up some false negatives, but are very unlikely to give you a false positive. These traits make the different tests most useful in different settings, Smith said. He uses rapid tests in the ER, where patients come in symptomatic and the most important thing is to be able to trust that a positive test result is for real. For broadly testing the general public, though, you’d rather use a test that produces fewer false negatives, so you don’t send asymptomatic carriers out with a false sense of confidence, he told me. The White House was using rapid tests.

There are a couple of personal lessons you can take away from the outbreak of COVID-19 within the administration. First, consider your pretest probability — or the chances you’ve actually been in contact with the virus. Your likelihood of being infected is different if you’ve been, say, hanging around in the West Wing of the White House, than if you’ve been social distancing in a low-COVID part of the country, Woloshin said. If you take a test, and it comes back negative, the person with a low probability of having COVID-19 in the first place has good reason to believe the test. The person who didn’t, on the other hand, probably shouldn’t give a negative test result too much credence.

Second, quarantines matter. If you know you were exposed to COVID-19 and you get a test and it says negative, you did not just get yourself a “Get Out of Quarantine Free” card. Even after day five, studies done on real world patients have found a 20 percent probability of a false negative test. The Centers for Disease Control and Prevention currently advises people who have been exposed to COVID-19 to quarantine themselves for 14 days from the day they were exposed. McEnany didn’t do that in the days before she tested positive. It’s now been eight days since Joe Biden was exposed to President Trump during the debate, and he tested negative that whole time. But he hasn’t stopped campaigning. “As long as I’m in the window period there’s no real guaranteed safe time,” Smith said.

Third, tests can be useful tools, but you should be very careful how you use them. Say you want to hang out with some friends you haven’t seen in months — so you all go get COVID tests in preparation for meeting up. If you’re all negative, you might assume you’re in the clear. But experts are a bit cringey on that plan. “I can’t say that’s a good idea,” Pritt said. “But knowing that what people do is not always going to follow the guidelines … I understand that.”

You can use tests to reduce risk, but that only works if you know the test is just a snapshot of a moment in time. Ideally, if you’re going to try to do a “hall pass” situation, you want more than just one negative test result. You want people who have no symptoms and no exposures. You would want to get a test that has a high sensitivity. And you want to be able to trust that the people you’re getting together with are isolating themselves before and after taking the test — so you know that they didn’t walk out of the testing clinic and get infected the next day. Nothing is 100 percent, Smith told me. But, if it was done carefully, he didn’t think a hall pass was the worst idea in the world.

Ultimately, despite all the complexities, the takeaway is pretty simple, Woloshin said. “It’s a big mistake to rely only on tests,” he said. “You still need masks, social distancing, hand washing, ect. Especially if you’re in an area where there are high rates of COVID.”