CDC warns of ‘Covid-19 rebound’ after taking Paxlovid antiviral pills

Some Americans who take Paxlovid, an antiviral for Covid-19, may see their symptoms rebound after a brief recovery, the Centers for Disease Control and Prevention said in an advisory Tuesday.

The Food and Drug Administration cleared Paxlovid for emergency use in December for people age 12 and older who have mild or moderate Covid but are at high risk for a severe case. This includes older Americans, people who are obese, smokers or pregnant women, and people with underlying medical conditions such as diabetes, HIV or cancer.

The drug regimen consists of three pills taken twice a day for five days. But two to eight days after completing treatment and testing negative, some patients may test positive again and see their symptoms return, the CDC said.

The opinion confirmed a trend that many patients and doctors have been discussing for at least a month. A case study published online in late April sequenced virus samples from a 71-year-old man who saw his disease rebound after completing Paxlovid. The study, which is being reviewed by a medical journal, found no indication that the man had developed resistance to the drug; instead, the authors suggested that symptoms could return “before natural immunity is sufficient to completely eliminate” the virus.

More recently, three prominent doctors documented so-called Paxlovid bounces within their own homes on Twitter.

Dr. Bob Wachter, chair of the department of medicine at the University of California, San Francisco, chronicled the case of his wife, Katie Hafner.

“While the rebound cases seem to be mild and self-limiting, the rebound is still a big disappointment,” he wrote on tuesday. “Katie was forced back into solitary confinement for about another week, her symptoms got worse…and she could have infected someone (including me!) if she hadn’t been extremely careful.

Dr. Tatiana Prowell, associate professor of oncology at Johns Hopkins, and Dr. Peter Hotez, dean of the National School of Tropical Medicine at Baylor College of Medicine, told similar anecdotes.

“Day 22 from the start. Still symptomatic. Rapid test always very positive. What do we do? Prowell tweeted on Monday.

“Either this post-Paxlovid relapse is real, something unique to BA.2.12 (though I can’t confirm that)…or something… We’ll figure this out eventually, but it’s still a puzzle” , Hotez wrote last weekreferring to an omicron subvariant that is now the predominant strain in the United States

The three experts said, however, that the rebounds do not necessarily mean that Paxlovid does not work. The Pfizer clinical trial showed that Paxlovid reduced the risk of hospitalization or death in high-risk Covid patients by 88% within five days of symptom onset. The National Institutes of Health still recommends it over other treatments for mild or moderate Covid.

Additionally, the CDC has so far identified no cases of serious illness among people whose symptoms or infection rebounded after taking Paxlovid. On average, patients whose symptoms returned or who tested positive again saw these second-round illnesses improve or resolve within three days. They did not require additional treatments, the CDC said.

The agency, however, recommended that people with Covid rebounds start their isolation again. The CDC has not yet determined whether patients with Covid rebounds are more or less likely to spread the virus than they were during their initial illness.

“A brief return of symptoms may be part of the natural history” of coronavirus infections for some people, whether they took Paxlovid or were vaccinated or boosted, the CDC said.

The Pfizer clinical trial identified similar rates of Covid rebounds among participants who recently completed Paxlovid and those who recently received a placebo.

Paxlovid must be taken within five days of being diagnosed with Covid. Some medical experts, including Wachter, have questioned whether patients would benefit from longer treatment. Other experts have questioned whether Paxlovid is being administered too early in an illness.

At least, the CDC said, rebound Covid cases don’t appear to be related to reinfection.

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