A recent preprint study found that rapid Covid-19 tests often returned false negatives in the early days of an infection—including in four cases where individuals actually transmitted the virus while testing negative.

Radio Advisory episode: Omicron—what it means for health care policy

Study details

For the study, researchers looked at 30 people who worked in settings in New York and San Francisco where they were required to be tested for Covid-19 daily—and, importantly, who were required to receive both a rapid antigen test and a PCR test.

The study found that all rapid tests used, which included the Abbott BinaxNOW test and the Quidel QuickVue test, remained negative on day 0 and day 1 of infection after a positive PCR test.

The omicron variant: The 'good,' 'bad,' and 'ugly' scenarios

In itself, it's not surprising that PCR tests were quicker to pick up early infections, as they're more sensitive to low levels of the coronavirus than rapid antigen tests. But strikingly, in 28 of the 30 cases where rapid tests returned a false negative, the viral levels detected by PCR testing were high enough that patients could have transmitted the virus to other people, the researchers said.

In fact, the researchers documented four cases in which an infected person actually transmitted the coronavirus while their rapid tests were still reporting negative results.

"It's absolutely likely there were many more than four transmissions," said Blythe Adamson, lead author on the study and principal epidemiologist at Infectious Economics. "There were likely many more."

The researchers concluded, "Based on viral load and transmissions confirmed through epidemiological investigation, most omicron cases were infectious for several days before being detectable by rapid antigen tests."

The study also found that viral loads peaked in the participants' saliva one to two days before it peaked in the samples taken from nasal swabs.

Discussion

Experts say the study suggests two things: that omicron behaves differently than previous variants of the virus, and that a negative rapid test doesn't necessarily mean a person does not have transmissible levels of the coronavirus.

"I think that with every new variant that comes, scientists have to question whether the things that were previously true are still true," Adamson said. "This one has a different way it travels, a different mechanism of action of symptoms, it has different windows of transmission."

"We know that PCR tests are more sensitive than antigen tests—this is not new information," Abbott Laboratories said in a statement. "We also know that PCR tests are so sensitive that they do not indicate infectiousness and thus are not a practical tool for keeping the workforce and economy moving."

The findings of a high viral load in saliva as opposed to nasal swabs is consistent with another preprint study from South Africa. This accumulating evidence "might be an indicator that that's where the virus is growing first," Gigi Gronvall, an immunologist and testing expert at Johns Hopkins Bloomberg School of Public Health, said. "So if you're going to look for the virus, which is what the tests do, then you may find more of it faster in the throat swab over the nose."

Ultimately, "[t]he message is not that we should stop using [rapid] tests," Isabella Eckerle, a clinical virologist at the University of Geneva in Switzerland, said. Instead, people should be careful in interpreting what a negative rapid test means, especially if they have symptoms or think they've been exposed to the coronavirus.

"It's not a ticket that allows you to go back to normal or to drop any other measures," Eckerle said.

"A negative result may not actually be a negative result," Anne Wyllie, a microbiologist at the Yale School of Public Health and an author on the study, said. "People should not ignore high risk exposures. They should not ignore symptoms." (Herper, STAT News, 1/5; Anthes/Jewett, New York Times, 1/5; Owens, Axios, 1/6)