When Dr. Anthony Fauci got Covid in June, he took Paxlovid, an antiviral drug for people with mild to moderate symptoms whose ages or immune statuses put them at high risk for severe disease. The treatment consists of three pills taken twice daily for five days.
Fauci finished the treatment and tested negative for Covid. But about three days later, a test came back positive again. His symptoms — runny nose, sore throat and fever — resurfaced, too.
A small minority of people who take Paxlovid see a similar rebound effect.
"When you look at the studies, it generally does not occur very often," Fauci, who directs the National Institute of Allergy and Infectious Diseases and is President Joe Biden's chief medical adviser, said Tuesday on MSNBC's "Morning Joe." But he noted that there have been "anecdotal cases" that suggest rebounds are more common now than they were in clinical trials.
Around 1% to 2% of people taking Paxlovid in Pfizer's clinical trial tested positive for the coronavirus after having tested negative. Rebound rates are around 5% among the tens of thousands of people who've taken the drug in real-life settings, the White House Covid response coordinator, Dr. Ashish Jha, said at a news conference last week.
"If you look at Twitter, it feels like everybody has rebound," Jha said. "But it turns out there's actually clinical data."
A small study in June found that less than 1% of Covid patients had their symptoms rebound around nine days, on average, after they took Paxlovid. In a larger study of 13,600 Covid patients, which hasn't been peer-reviewed, 6% had their symptoms rebound in the month following the treatment.
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Dr. Aditya Shah, an infectious disease specialist at the Mayo Clinic who led the small study, said it's difficult for people to self-diagnose rebound cases. Ideally, people would have proof that they tested positive, then negative, then positive again, he said.
The real number of rebound cases "could be as high as 5 to 10%, but I don't think it is as common as the general community is making it out to be," Shah said.
The Centers for Disease Control and Prevention said in May that symptoms usually rebound two to eight days after Paxlovid is stopped, if they come back at all.
People who continue to test positive may still be contagious, so the CDC recommends that people restart isolation for at least five days if their illness returns.
The treatment may not be long enough
Some disease experts suspect the Paxlovid regimen is too short to clear the virus in certain people.
"One of the theories is that your natural immunity just can't kick in quickly enough, since you have to treat within five days of symptoms, so that's pretty early on in the course" of illness, said Dr. Peter Gulick, an associate professor of medicine at Michigan State University.
When someone takes Paxlovid, "it probably knocks that viral load down to a point where the body's not reacting to it clinically with any kind of inflammation," Gulick said. That would explain why symptoms initially resolve within about five days.
But some people may still have lingering virus in their bodies, particularly if they had high viral loads to begin with or the virus spread to areas that drugs can't easily reach. In that case, symptoms could come back.
"There might even be reservoirs," Gulick said. "We don't know Paxlovid's ability to get into certain little areas of the body where the virus may be."
Shah, however, isn't sure that extending the treatment course would benefit patients: "I would be hesitant to say right now, 'Yeah, sure, take a 10-day course,' because that has zero evidence to support it."
Disease experts said that it's possible that older or immunocompromised people may be more likely to have symptoms rebound or to test positive again after having taken Paxlovid but that there's no good data to support the theory yet.
In any case, rebounding symptoms should be mild. A June CDC study found that less than 1% of people taking Paxlovid were admitted to the hospital or the emergency department for Covid in the five to 15 days after they stopped the treatment.
"Paxlovid is working really well and preventing serious illness, rebound or no rebound," Jha said last week. "That's why the president took it."
Biden finished his five-day course of Paxlovid on Monday. Experts said he should know whether his symptoms have rebounded in the next few days.