CU Boulder research finds waiting two days improves accuracy of at-home COVID tests

In a new study, University of Colorado Boulder researchers found that if only one at-home test is available, the most accurate results for COVID start two days after the start of symptoms. For the flu and respiratory syncytial virus, however, it’s recommended to take a rapid test immediately after symptoms arise.

The study used a mathematical model to answer questions about at-home rapid test timing and accuracy, not only for COVID but also for emerging tests for RSV, the flu and other infectious diseases.

“You cannot use the same test in the same way and expect to get the same results for different pathogens, or even different variants,” said Casey Middleton, first author of the study and a doctoral student in the CU Boulder department of Computer Science and the IQ Bio program.

For COVID testing, the reason it’s better to wait a couple days before testing lies in how the rapid tests detect disease, and their surprisingly high false negative rate when used too soon.

“Especially really early on for COVID, when your symptoms first start, we find that if you take that one test right away, there is a 95% chance that a negative result is a false negative,” said Middleton.

Waiting two days after symptoms brings that rate down to 70%. For those who can afford to take a second test on day three, the false negative rate dips lower, with the tests catching about a third of infections.

Rapid tests are built to detect those who are the most infectious, said Daniel Larremore, senior author of the study and a CU Boulder professor of computer science at the BioFrontiers Institute. So, if the amount of virus in a patient is relatively low — such as in the beginning stages of an infection, especially in someone who has built up an immunity — the rapid test may produce a false negative.

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“It’s not that we were using tests incorrectly before, in fact, for the founder strain of SARS-CoV-2, if you felt symptoms, yeah, you should test right away,” said Larremore. “But the virus has changed, and humans’ immune systems have also been updated with vaccinations and infections, and so the way that our bodies respond has also changed. We get the signal that we’re infected a lot earlier now from symptoms.”

Middleton clarifies that while the risk of so many false negatives sounds worrying, making the tests sensitive to those who are the most infectious is an efficient way to keep transmission rates low.

“If you think about who you care most about detecting, those who have the highest viral loads — the most virus inside of them — are really who we would prefer to catch, and rapid tests are still really highly linked to your infectiousness,” said Middleton. “Thinking about the population as a whole, if we can just catch those people who have the most virus, that can still be really productive for preventing transmission.”

As the COVID landscape continues to change, so should best practices when it comes to testing. Because of at-home tests’ high false negative rate — especially in those with built-up immunity — it’s important to continue to test throughout the illness period if there are tests available.

“Maybe that negative test result should not be entirely believed if you still have symptoms, and (you should be) making sure that you are just staying home as long as your symptoms persist,” said Middleton. “If possible, when you still have symptoms two days later, go ahead and go get another one of those rapid tests.”

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Assuming that enough at-home tests are available, the study also suggests that a “test to exit” strategy — in which people test again before determining whether to return to work and socialize — can prevent more COVID infections with less inconvenience than the five-day isolation policy that was standard Centers for Disease Control advice until March.

“There have been enormous investments made in the U.S. and around the world in the next generation of diagnostic tests,” said Larremore. “We can expect that testing in the next decade is just going to get better and better and better. That means an earlier ability to detect, fewer false negatives, fewer false positives, and the price points should continue to drop.”

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