Why a negative Covid-19 test before Thanksgiving isn’t an all-clear

More frequent Covid-19 testing is one key to help end the pandemic. But as individuals, we can’t rely on testing alone to protect ourselves and others.

Take this recent example: Public health officials in New Zealand reported on a cluster of cases that likely spread aboard a long-haul flight. Yet the suspected index cases — the people who likely spread the virus to others — tested negative for the virus a couple of days before boarding their plane in Switzerland and thought they weren’t infected.

This goes to show: A negative test is not an all-clear in terms of being able to safely interact with others without masks or other precautions. “Testing negative is not like a passport for people to go out and do whatever they want to do,” as Muge Cevik, a virologist and physician at the University of St. Andrews, told me earlier this fall.

As people make (unwise) plans to travel this Thanksgiving week, they should understand that testing negative does not mean it’s safe to be in close contact with other people. It does not mean it’s safe to take masks off.

Scientists don’t yet know exactly when a person who is infected with the coronavirus will start testing positive for the virus. There are situations when a person could test negative, be infected, and also be contagious. It’s also possible — since the virus multiplies itself exponentially in the body very quickly — that someone could test negative in the morning (and not be contagious), but by the afternoon test positive (and be very contagious).

Confusing? Yes, it is. But the bottom line is that Covid-19 diagnostic tests (both the slower, more common, viral genetic test — called RT-PCR — and the more rapid viral protein test, called an antigen test) are most accurate when used on people experiencing symptoms.

“One of the huge gaps now in the data is: What is the probability of testing positive before you get symptoms?” Benny Borremans, a disease ecologist at UCLA, said in October. Right now, scientists just don’t know for sure.

Why testing is less accurate before symptoms begin

There are several reasons scientists are unsure about when people will start testing positive for SARS-CoV-2. To understand why, and to make this less confusing, it’s helpful to think through all the things that have to happen for a Covid-19 test to come back positive.

First, the virus needs time to establish itself in a person’s body. This is called the incubation period, and it can take upward of two weeks. On average, this happens in about five or six days. During the incubation period, a person might not test positive because there’s not enough virus in their body to detect in a test.

“The virus particles, day by day, will multiply,” Cevik says. “The virus needs to reach a threshold for the PCR [i.e. viral genetic] tests to pick it up.” PCR is the more common Covid-19 diagnostic test because it requires a lower threshold of the virus to test positive; rapid antigen tests would require a higher level of virus to register a positive test.

Testing positive should coincide with being contagious. But it doesn’t always.

Generally, a person can start being infectious for the virus around two days before they start to show symptoms, in what’s known as the presymptomatic phase.

And, generally — but not always — scientists would expect that if a person is contagious, they’d test positive. After all, if they’re spewing enough virus out to get another person sick, they’re probably spewing enough virus out for a diagnostic test to pick up.

But when exactly a person makes the jump from testing negative and being non-infectious to testing positive and being infectious is hard to predict.

“If everything works as it should, the test should be positive if you are infectious at the very moment of the test, as there must be virus present then,” Justin Lessler, an epidemiologist at Johns Hopkins University, says. “However, you could easily test negative then become infectious a day, or even hours, after the test.” Unless you’re testing every hour, it’s impossible to get a fine-grained view on when the infectious period truly begins. (Also possible, but probably rarer: A person tests positive before they start to be contagious.)

Even if a person is contagious, they may not test positive. It could come down to where the sample for testing was taken from.

In general, “we consider the gold standard to be the nasopharyngeal swab,” Bobbi Pritt, the director of clinical microbiology at the Mayo Clinic, says. “That’s the deep nasal swab that goes all the way back into the back of your nose. Whereas other specimens — like a throat swab or just the very outer edge of your nose, like right inside your nostril — that’s not going to contain as much virus.”

Early on in the infection, a person who is incubating the virus is expected to test negative. Over the summer, Johns Hopkins researchers — including Lessler — published a paper estimating the likelihood of a false negative test in the first few days after being exposed to the virus. On the first day, they found the chance of a false negative near 100 percent. No test is going to find the virus so early. Through the first four days, that rate drops to 67 percent on day four, on average, but with a very large range of error. On the day people first reported symptoms, there’s still a significant false negative rate, at 38 percent.

What does this all add up to? “What we’re saying is don’t test anyone in less than four days after exposure,” Cevik says. It’s not going to tell you much about the person’s status. Or if a person is tested in that time, they ought to be retested a few days later.

“In general, five to eight days after exposure is the best time to test,” Cevik says. “Or day three after symptom onset.” That’s when the genetic RT-PCR tests are most likely to reveal a true positive.

Because nothing about Covid-19 can be simple, here’s another thing to consider: The antigen tests that produce quick results have a shorter window in which you’d expect a person would test positive.

They are also slightly less accurate, but this limitation can be overcome if they are used repeatedly. If used correctly, these tests will flag a positive in the window when a person is most likely to be contagious. And with repeated use, scientists hope these quick tests could help stop outbreaks from growing out of control.

A negative test without symptoms might not mean much. Keep your mask on.

Here’s the bottom line: “We don’t know when one will test positive pre-symptom onset for PCR or antigen tests,” epidemiologist A. Marm Kilpatrick writes in an email. He points to a few papers that try to quantify the probability of testing positive while asymptomatic, but they are hard to draw conclusions and recommendations from.

That’s because the incubation period — the time it takes from initial exposure for a person to become infectious — can vary greatly from person to person. (It can happen in four or five days, or up to two weeks.) “If someone has a long incubation period, our [work] suggests their infectiousness rises later and thus there would be a longer period where they’d test negative.”

If you have symptoms, you’re likely to test positive the day you start feeling ill, but not guaranteed. The first few days after starting to feel sick, you have a very high probability of testing positive.

We could learn more in the months ahead about testing asymptomatic and presymptomatic people, with studies following people after they have been exposed to the virus, and testing them repeatedly over a few weeks to determine the likelihood of testing positive before symptoms begin. “We have a lot of data from symptom onset onwards, but we don’t have data in terms of presymptoms,” Cevik says.

This is why testing is no replacement for other Covid-19 mitigation measures, like quarantining people exposed to the virus, mask-wearing, and social distancing. Please, please remember this.

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