However, some people who take Paxlovid — and some who don’t — experience a rebound case of Covid-19, with a resurgence of symptoms or positive tests just days after completing treatment and testing negative.
And recent high-profile rebound cases, including President Joe Biden, Dr. Anthony Fauci and first lady Jill Biden, are raising questions about just how frequently this happens.
“From the data we have so far, Covid-19 rebound is a relatively infrequent event — this is not happening the majority of the time,” a spokesperson from the US Centers for Disease Control and Prevention told CNN. “A small percentage of people with Covid-19 experience a rebound of symptoms, including those who take antiviral medication, such as Paxlovid.”
Experts say that rebound cases are probably more common than data suggests, but it’s difficult to know by exactly how much.
There’s a wide range of estimates for what that “small percentage” might be — from less than 1% of people who take Paxlovid to more than 10% — and definitions of a rebound case are lacking consistency.
It’s important to get a better handle on the specifics for both individual patients and the broader community, says Dr. Michael Charness, of the Veterans Administration Medical Center in Boston, who has collaborated with a team of researchers at Columbia University to look into cases of Covid-19 that return after Paxlovid treatment.
People experiencing a rebound case can be contagious, so they should be aware of the possibility that they might need to reisolate in line with CDC guidance, he said. And for others, the return of symptoms or a positive test can “certainly be a source of concern for many people, wondering ‘Why is this happening to me?'”
Tracking Covid-19 rebound
Pfizer does not have additional data on rebound cases beyond the clinical trials, which were conducted during a time when the Delta variant was dominant and the majority of people were unvaccinated.
But according to Aditya Shah, an infectious disease specialist and an author of the report, the true rate is probably closer to 10%.
“You have to acknowledge the limitations of doing this kind of study. All these patients are home, and not every patient who has rebounded symptoms is going to contact their doctor,” Shah said. “So our study definitely had an under representation of true cases.”
Charness also estimates that the Covid-19 rebound rate for vaccinated people who have taken Paxlovid is in a similar range, but uncertainty remains.
“There has not been a study that gives us a clear answer. It’s probably not 50%, and it’s probably not 2%,” he said. “I wouldn’t be surprised if it’s in that 5 to 10% range for people who are treated in the 1 to 2% range in people who are untreated.”
According to the CDC, preliminary data suggests that people with comorbidities may be more likely to experience a rebound case. However, studies to examine risk factors are “ongoing” and “there is no conclusive evidence at this time and more research is needed” they said.
‘Rebound is going to be an inconvenience’
Despite the potential for a rebound case, experts agree that Paxlovid is still a good treatment option.
If a rebound case of Covid-19 is one cost of taking Paxlovid, but it must be weighed against the costs of what could happen with no treatment, Charness said.
The vast majority of people who have a rebound case of Covid-19 after taking Paxlovid have been found to have mild symptoms. Sometimes they may come back stronger, as in Fauci’s case, but they remain far from the levels of severe disease that Paxlovid is meant to protect from.
“I think that, especially for people who are at significant risk for progression, it’s important to take Paxlovid,” he said. “A percentage of those people — yet to be determined — are going to have rebound. But in almost all of those people, the rebound is going to be an inconvenience. And that inconvenience, really, is not as important as the potential of avoiding hospitalization or death.”
Both President Biden and Fauci received a second course of Paxlovid to treat their rebound cases. And just this week, the FDA requested more data from Pfizer to study patients who may need a second course of treatment.
“While further evaluation is needed, we continue to monitor data from our ongoing clinical studies and post-authorization safety surveillance,” Pfizer said in a statement. “We remain very confident in its clinical effectiveness at preventing severe outcomes from COVID-19 in patients at increased risk.”
In terms of rebound cases, Charness says a lot of work has been done, but many questions remain.
“I reflect back to February and March when this was something that really wasn’t known and when people who experienced rebound were calling their providers and being told as a test must be wrong,” he said. “Between then and now, there’s been a huge dissemination of information, which is a good thing, but people aren’t 100% sure how to handle it.”