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Paxlovid rebound: Why Biden tested positive again after taking antivirals

Some people, including President Biden, may test positive for COVID-19 again after taking antiviral medications.
/ Source: TODAY

Like many Americans, President Biden tested positive for COVID-19 last month. But, following his infection, Biden experienced something a little less common: Paxlovid rebound.

Biden initially tested positive on July 21, according to a statement from his physician. He received the antiviral medication Paxlovid, which can help prevent severe COVID-19 disease in people with underlying risk factors for more serious symptoms. Biden completed his five-day course of Paxlovid and tested negative on July 26.

But a few days later, on July 30, he tested positive again on an antigen test — and went back into isolation. Initially, Biden reported that his symptoms hadn't come back. But this week the president is "experiencing a bit of a return of a loose cough," his physician wrote in a statement on Tuesday.

The decision to go back into isolation after rebounding was a good one, Dr. Taison Bell, assistant professor of medicine in the divisions of infectious diseases and international health and pulmonary and critical care medicine at the University of Virginia, told TODAY. "But it just demonstrates how difficult it is to really know exactly what to do in all these circumstances," he said.

As if COVID-19 isolation protocols weren't confusing enough, a rebound can make them even tougher to navigate.

What is Paxlovid rebound?

It's not entirely clear why some people develop a COVID-19 rebound after taking antiviral medications like Paxlovid and Lagevrio. These drugs work by suppressing SARS-CoV-2, the virus that causes COVID-19. So one theory is that the five-day course simply isn't long enough and leaves enough virus in people's bodies to reemerge as a rebound, NBC News explained.

Experts aren't sure how many people experience a rebound after taking antiviral medications, Dr. Ashish K. Jha, White House COVID-19 response coordinator, wrote on Twitter after the president tested positive again.

"In the clinical trial, the placebo group had almost as much rebound as Paxlovid group. Both groups about 2% of the time," he wrote. Looking at data from large health systems, rebound appears to occur between .05% and 10% of the time. "I know, big range," Jha wrote. "My best guess based on today’s data? About 5%."

Not everyone who tests positive again also develops rebound symptoms, Bell explained. So it's possible that Paxlovid rebound happens more often than we realize, but people aren't thinking to test because they don't feel sick again.

"If this was someone in the community who didn't have a physician following him around everywhere he went and wasn't getting tested every day, I suspect this is a person who would just be going about their normal activities," Bell said.

Case reports so far indicate that a rebound likely isn’t a reinfection, Dr. Emily Volk, president of the College of American Pathologists, told TODAY. “It also does not mean you’re resistant to the Paxlovid,” she said.

It’s worth noting that COVID-19 can cause a rebound on its own: "A brief return of symptoms may be part of the natural history of SARS-CoV-2 infection in some persons, independent of treatment with Paxlovid and regardless of vaccination status," the Centers for Disease Control and Prevention explain in a May health advisory.

A recent study found around one-third of people with COVID experience a rebound of their symptoms, regardless of whether they took Paxlovid, NBC News reported.

Are you still contagious if you rebound?

If you're still testing positive near the end of your infection or you test positive again after getting a negative result, you're less likely to infect others than you were at the beginning of your infection, experts told TODAY previously. But it's still best to err on the side of caution and take what precautions you can until you're in the clear.

The CDC recommends that anyone who might be experiencing a rebound follow the usual isolation guidelines.

"The reason to test is to say, 'OK, am I going to be safe to be around my loved ones or my colleagues who are vulnerable?" Volk said. "And if you have a test that says it's positive, you might not be safe." 

While it's not necessarily possible for everyone to stay home as long as recommended after testing positive again, you should stay home if you can, Volk recommended. And if you can't, take as many precautions as you can to keep those around you safe, including wearing a mask, she said. "It's really like being a good neighbor."

But it's important to remember that "transmission is not a binary thing," Bell said. "It depends on so many factors," including the precautions that people on both ends of a potential interaction are taking, like wearing masks.

So, it's challenging to say with certainty whether or not someone going through a rebound is or isn't going to spread the virus to others. But if they're testing positive, the chance is "high enough to justify going back into isolation putting on a mask," Bell said.

"Paying attention to rebound is important," Jha wrote, "because when you rebound, you can potentially be contagious." But it's “key” to remember that rebound doesn't seem to lead to severe symptoms or hospitalizations, he added.

Essentially, Paxlovid is doing what it was designed to do and keeping people out of the hospital. So if you take an antiviral medication, know that you might also experience a rebound, Bell said. "Be prepared for that possibility."

And don't let the possibility of a rebound keep you from taking the medication if your doctor thinks you could benefit from it. "(The) relatively rare phenomenon of COVID-19 rebound should not discourage anyone who needs to take Paxlovid because they are in a high-risk group," Volk said.