Seeing that bright red line appear on an at-home Covid-19 test can feel inevitable during a surge like the one under way now. What can be surprising is how many days later that line keeps popping up.

The Centers for Disease Control and Prevention recommends five days from first symptoms or diagnosis as a minimum isolation period before infected people can return to public activities while maintaining certain precautions. Yet some people continue to test positive for the Covid-19 virus on rapid tests beyond those five days. Some even test positive after 10 days and after symptoms have resolved.

The question then becomes: How long are people infectious? Into the pandemic’s third year, as new, more infectious variants continue to circulate widely and more people have built-up immune defenses, researchers aren’t totally sure when or how long individuals with Covid-19 might be contagious and shedding virus, particularly at the end of an infection.

“It’s still up for debate,” said Nathaniel Hafer, director of operations for the University of Massachusetts Center for Clinical and Translational Science.

The isolation guidance that the CDC updated amid Omicron’s rapid spread is likely leading some people to leave isolation while they are contagious, some health experts and clinicians said, particularly if people don’t wait for a negative rapid test and aren’t wearing high-quality masks for a full 10 days.

“We know that people will be returning to work while they’re still infectious, even if they feel better,” said Carina Marquez, an associate professor and infectious-disease doctor at the University of California, San Francisco.

Dr. Marquez said she tested positive on an at-home test for 13 days recently, a period when she decided to work remotely. For those without that option, Dr. Marquez said that they should stop isolating after getting a negative rapid test, or they should stop isolating after 10 days and wear a mask, whichever comes first.

No test can perfectly tell whether someone with Covid-19 is contagious.

Photo: Justin Sullivan/Getty Images

The CDC recommends that everyone wear a well-fitted mask and avoid travel and being around high-risk people for 10 days, no matter when the person leaves isolation.

The CDC didn’t immediately comment on its guidance.

No test can perfectly tell whether someone with Covid-19 is contagious, infectious-disease experts and laboratorians said. A more accurate indicator is culturable virus, a test of whether a virus sample taken from a patient can infect cells in a lab. But such tests are complex and can only be run in labs with certain safety protocols.

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Several studies suggest that positive results on rapid antigen tests such as the iHealth, QuickVue and BinaxNow often match with culturable virus results. Some public-health experts have encouraged people to use at-home tests as a gauge for infectiousness, especially since they have become more widely available.

The tests often only turn positive when a person is carrying large amounts of virus. At the beginning of an infection, when a person’s viral load is rising, it might take a few days before tests turn positive. That is why health authorities recommend that people with symptoms and negative rapid-test results wait and retest or get a more sensitive lab-based PCR test.

As a person’s viral load drops, rapid tests are a better indicator of who is no longer infectious, public-health experts said. The University of Chicago started deploying the tests in December to figure out which healthcare workers could safely come back to work and help alleviate staffing shortages before 10 days of isolation, said Emily Landon, UChicago Medicine’s executive medical director of infection prevention and control.

More than 40% of 260 healthcare workers who felt well enough to work were positive the first time they took a rapid test between days five and 10 of an infection, Dr. Landon and her colleagues found, according to a preprint study that isn’t peer-reviewed.

“We didn’t feel comfortable having them come back,” Dr. Landon said.

The CDC has said data shows that most transmission occurs early in the course of infection and that peak infectiousness declines within a week of symptom onset. Much of that data was gathered before the emergence of an Omicron variant much more infectious than those that preceded it.

More recent studies have demonstrated that a significant portion of people test positive on rapid tests after five days, including one published by the CDC in February that found 54% of people had positive rapid-test results between days five and nine after symptoms or diagnosis. The percentage of positive results declined over time. The authors wrote that the evidence reinforced the importance of mask use during that period and that rapid tests could be a useful tool for guiding isolation recommendations.

Studies have found that a negative rapid test after an initial diagnosis is a solid sign that a person is likely no longer contagious.

Photo: John Tully/Bloomberg News

One recent study found that only 17% of vaccinated college students had culturable virus beyond day five, while a separate study of people with mild Covid-19 cases found more than 50% had culturable virus at day five and 25% did at day eight. Neither study has been peer-reviewed.

“It does make us concerned that people are still able to transmit at day five or day eight,” said Amy Barczak, an infectious-disease doctor at Massachusetts General Hospital in Boston and senior author of one of the studies.

Both studies found that a negative rapid test after an initial diagnosis is a good indicator that a person no longer has culturable virus and a solid sign they are likely no longer contagious. With a positive rapid-test result toward the tail end of the 10 days, however, it can be more difficult to tell how infectious that person might be, especially if they are feeling better and the line is growing fainter.

“You should consider yourself potentially having transmissible virus,” said Tara Bouton, an assistant professor of medicine at Boston University School of Medicine and lead author on another one of the studies. People who stop isolating before 10 days should wear a high-quality mask like an N95 and keep contacts to a minimum, Dr. Bouton said.

Immunocompromised people and those who get severely ill can be contagious even longer, studies suggest, and patients who experience rebounding symptoms or who test positive again after taking Pfizer Inc.’s Paxlovid pill should also assume that they are contagious, infectious-disease experts said.

Generally, studies suggest it is rare for virus to be culturable after 10 days. Infectious-disease experts disagree about whether most people should continue to test beyond that point.

“These tests aren’t perfect,” UChicago’s Dr. Landon said. “They underestimate contagiousness in the beginning of illness and overestimate at the end…but not by that much.”

Write to Brianna Abbott at brianna.abbott@wsj.com