Coronavirus FAQ: I'm confused by the new testing advice! Do it once, twice ... thrice?

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So you had dinner – indoors – with a friend and the next day got a call from your dining companion: "I hate to tell you – but I'm now testing positive for COVID." Uh oh, did you catch it from your friend?

Or you wake up in the middle of the night with a scratchy throat, a cough and a feeling that your head is going to float off your neck. Could it be COVID?

In both these scenarios, the question about whether or not you have COVID can be answered by a self-test or a PCR test. Many people opt for the self-test option since you can now easily pick up self-tests and get an answer in 15 minutes in the comfort of your home.

But if you take an at-home test and it's negative ... are you really in the clear?

That's a question the CDC and the FDA are addressing in guidance issued yesterday on COVID protocols. And there's a little bit of confusion.

The CDC says that if you were exposed to COVID, "instead of quarantining" you should wear a "high-quality mask for 10 days and get tested on day 5. If that test is negative, the CDC thinks you're good to go. And if you think you are sick and that it might be COVID-19, "isolate" until you get test results. The CDC states: "If your results are negative, you can end your isolation."

The FDA, however, now says that one negative test isn't enough. Here's what the FDA advised in a "safety communication" released on August 11: If you have symptoms, you should take another test 48 hours later. If you don't have symptoms, you should take three tests, each 48 hours apart. Only if all those tests are negative should you consider yourself to be COVID-free.

And the FDA isn't the only one to think repeat testing is the way to go. Infectious disease experts agree that the only way to be sure you don't have COVID after a negative home test, is to test again – either with another home test or a more sensitive PCR.

Okay... so why am I being asked to redo my home tests if they're negative?

We get it, repeat testing isn't the most convenient thing. The problem is that those home tests aren't especially sensitive at the beginning of a COVID infection.

"There is a recognition that [at-home rapid antigen tests] are less sensitive than PCR tests," says Dr. Apurv Soni, professor at the University of Massachusetts School of Medicine. "But it's not that they don't work, it's just that we need a better understanding of what an effective testing regimen should be."

The FDA made its recommendations based on a yearlong study it did in collaboration with the NIH and University of Massachusetts School of Medicine that was released preprint on medRxiv on August 6.

That study showed that if you take a home test on the day you get a COVID infection, there's a good chance it's going to come back negative – meaning you could be infectious but a home test won't yet show it.

"The data very convincingly show" that if you take another test or two, you can be pretty sure if you have COVID or not, says Soni, who was the lead author on that paper.

Soni says, "If you are concerned about having an infection and you have symptoms, you should take two tests 48 hours apart. If you do not have symptoms, you should take three tests, one every 48 hours. That's it."

So why aren't home tests great at picking up COVID infections? I thought that's what they were supposed to do.

Okay, so now that we know officially know that a single at-home rapid test isn't particularly great at detecting an early case of COVID, the question is: Why not?

Scientists estimate that 95% of the U.S. population has some amount of immunity to COVID due to vaccination or previous infection.

"We're more immune to the virus than we were in 2020," says Soni. "So the way your body reacts to the virus is different than it was in 2020. Antigen tests [home tests] are really good at detecting infection when the viral load is above a certain threshold." But because of the various degrees of immunity most people now have, "the rate at which the viral load increases in your body is slower."

After another few days though, the amount of virus in your body will probably be high enough to be picked up by a home test.

Does the FDA recommendation to repeat test have anything to do with omicron or the new subvariants?

The good news is that it doesn't seem like omicron is having any effect on the sensitivity of the tests. "The currently known variants do not affect the result of the rapid test," says Meriem Bekliz, postdoctoral researcher in emerging viruses at the University of Geneva.

Bekliz is the lead author on a paper published on August 8 in Microbiology Spectrum showing that there's not a difference in how a home test picks up the delta variant and the first subvariant of omicron, BA.1.

But what about the new BA.4 and BA.5 variants? New research shows that those variants are particularly adept at evading your immune system, but are they just as good at evading detection from your at-home rapid tests?

"The rapid home antigen-based tests can detect [all the] omicron subvariants," says Dr. Preeti Malani, professor of medicine at the University of Michigan. "The home tests do not rely on the spike protein, which is where the mutations occur in variants."

The spike protein is what our immune system looks for to identify and neutralize COVID. It's what many of the vaccines are based on. And its why changes in the spike protein have allowed new variants of COVID to somewhat evade detection by our vaccine-primed immune systems.

The home rapid antigen tests detect a different protein, the nucleocapsid. And all of the omicron subvariants have the same version of the nucleocapsid. What does that mean? "Theoretically, there should be no difference in detection sensitivity between omicron BA.1 and its sub-variants [including BA.4/BA.5]," Bekliz says.

What if after two tests 48 hours apart, I'm still sick and still testing negative?

So yeah, maybe you just don't have COVID. "There may be an alternative virus or even a bacterial infection like strep throat, causing illness and not COVID," says Malani.

Still, two negative tests 48 hours apart isn't 100% definitive. "Besides repeating the home test, you can also consider testing with PCR," Malani says.

PCR tests are more sensitive to lower viral loads than the at-home rapid antigen tests. So if you take a PCR test while sick and it comes back negative, then you can be fairly comfortable knowing it's not COVID.

However, just because you don't have COVID doesn't mean you are OK to head into the office. "If you are ill, whether due to COVID or some other virus, you should stay away from others," says Malani.

So does this really mean if I have dinner with a friend who then tells me they have COVID that I need to test three times over six days?

This is where things get a bit tricky. Even Soni admits that testing for that long, "is a little impractical." But he also says: "If you do repeat a test [ahead of whatever social event you want to go to] that gives you the highest confidence that you're not infected and therefore not passing infection on to others."

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