By Jennifer Henderson

As high levels of COVID-19 transmission persist, people continue to wonder how long they should isolate after learning they're infected.

One especially perplexing predicament is what to do when you continue to see positive results on a rapid antigen test, but it's been 5 days (or more) and your symptoms have resolved.

So, what could cause someone to continue to test positive?

It may be due to weakened virus that continues to replicate, said Benjamin tenOever, PhD, a microbiologist at NYU Grossman School of Medicine. It may also happen as a result of broken virus genomes.

Because the Omicron variant tends to stay localized in the upper respiratory tract, especially in those who are vaccinated and boosted, that may lead to more nucleocapsid protein in the back of the throat and nose, he said. And broken virus genomes can remain present after viruses make bad versions of themselves.

"If you are testing antigen positive, you should assume a low level of virus infection," tenOever said. "You are possibly transmissible."

This possibility may be difficult to grapple with on the heels of recently updated guidance from the CDC.

Last month, the CDC announced that those testing positive for COVID-19 could isolate for just 5 days if they are asymptomatic, down from a previous recommendation of 10 days. Though the CDC has since clarified that rapid antigen testing towards the end of that period is the best approach, the agency hasn't directed people to seek it out.

This approach differs from that of the U.K., which just this week updated its own guidance to say that people can stop isolating after 5 days only if they have two negative rapid antigen tests taken on consecutive days.

The first test should not be taken before the fifth day after symptoms have started (or the day a test was taken if symptoms were not present), the U.K. Health Security Agency stated. The isolation period remains 10 days for people without negative results from two tests on consecutive days.

The CDC noted that the reduced isolation period was prompted by data that suggest most transmission "occurs early in the course of illness, generally in the 1-2 days prior to onset of symptoms and the 2-3 days after."

A paper published in December, and cited by CDC in its updated guidance, found that "[e]vidence from 113 studies done in 17 countries shows that SARS-CoV-2 viral RNA can be detected as early as 6 days before symptom onset, concentrations peak around the time of symptom onset or a few days later, and it usually becomes undetectable from upper respiratory tract samples about 2 weeks after symptom onset, and with no substantial differences between adults and children."

These studies suggest that "the mean period of infectiousness and risk of transmission could be restricted to the period between 2 and 3 days before and 8 days after symptom onset."

However, these data pre-date the Omicron surge. And the CDC's latest approach to isolation isn't foolproof.

A new study from Harvard University that looked at a small number of cases from the National Basketball Association's COVID-19 testing program found that more than half of Omicron cases identified within a day of a previous negative test were still infectious 5 days after a first positive test, dipping to 25% on day six and 13% on day seven. The study -- which was not peer-reviewed -- used PCR testing.

Isolation periods, testing out of them, and the possibility of lingering infectiousness are definitely being discussed in medical circles, said Geoffrey Baird, MD, PhD, chair of the department of laboratory medicine and pathology at the University of Washington School of Medicine in Seattle. This is especially relevant when it comes to staffing shortages that are occurring across the country.

Overall, the question of "what is the real value of the test on any one specific day" persists, Baird said. "This is the challenge of doing public health."

It's about striking a balance between what is "medically right and accepted by the population," he added.

Ultimately, the country will need to determine how it will use rapid antigen tests going forward and whether that includes testing out of isolation, he said.

The percentage of people that would continue to test positive days or even weeks after their symptoms have subsided is likely very limited, tenOever pointed out. If it is well beyond 10 days and you are still testing positive, seeking out further medical advice or evaluation may be warranted.