CDC on Tuesday issued a warning saying that patients who complete a five-day course of Paxlovid and experience a return of Covid-19 symptoms should isolate for an additional five days, marking the first guidance the agency has issued on what patients should do if they test positive for Covid-19 days after testing negative.

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'Viral rebound' after completing Paxlovid treatment

Paxlovid, an oral antiviral Covid-19 treatment, was first authorized for emergency use by FDA in December. According to clinical trial data, the drug was able to reduce the risk of hospitalization or death by almost 90% in unvaccinated patients at high risk of severe Covid-19 outcomes, leading many health experts to call the treatment a "game-changer."

However, a growing number of patients are now reporting cases of "viral rebound" after finishing Paxlovid. In such an event, individuals have reported finishing the five-day treatment, feeling better, and testing negative on an at-home rapid test. But then, their Covid-19 symptoms return, and they test positive again a few days later.

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A preprint case study reported that a 71-year-old man, who was fully vaccinated and boosted, saw his virus rebound after taking Paxlovid. The patient initially took Paxlovid the day his symptoms began and was symptom-free two days later. However, after a week, he was sick once again, with his symptoms lasting for roughly four days the second time.

Genetic sequences of the virus showed that it was the same throughout the patient's two symptomatic periods, indicating that it was not a reinfection from a different virus. In addition, researchers did not identify any mutations that would suggest it had developed a resistance to Paxlovid.

Previously, Pfizer reported that a small percentage of clinical trial patients saw their symptoms rebound roughly 10 to 14 days after starting Paxlovid, but the company noted that viral rebound had also occurred in similar rates among patients who received a placebo during the trial. Now, anecdotal reports and Twitter surveys have found that as many as 47% of respondents who took Paxlovid say they went through a rebound, USA Today reports.

CDC issues isolation recommendation after Paxlovid rebound

Previously, it was not clear whether patients experiencing a viral rebound of Covid-19 symptoms are contagious and should continue isolating or seek another course of treatment.

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Now, a study from a team of Boston researchers, which has not yet been peer-reviewed, found levels of live virus in various rebounding patients for up to 11 days after completing Paxlovid, the Boston Globe reports.

"This strongly increased the suspicion that they are contagious," said Mark Siedner, an infectious disease clinician and researcher at Massachusetts General Hospital and coauthor of the study. "It's not just that they rebound. It's that they rebound and it seems like they start from the beginning, their virus goes way up," Siedner said. "It's a really unique phenomenon."

CDC says those who experience such a rebound should isolate for an additional five days.

"If you get better and then you get worse again or if you decide to test and you have a test that's positive, especially after a negative test result, the recommendation is to re-isolate for at least five more days and continue masking for at least 10 more days," said Lauri Hicks, CMO of CDC's Covid-19 response.

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Although this guidance is specific to those who rebound after taking Paxlovid, Hicks said anyone who tests positive or feels poorly again should stay away from others.

CDC added that there's "currently no evidence that additional treatment is needed with Paxlovid or other anti-[coronavirus] therapies in cases where COVID-19 rebound is suspected" and noted that a return of symptoms may be part of the natural course of the coronavirus in patients, "independent of treatment with Paxlovid and regardless of vaccination status."

Daniel Griffin, an infectious disease specialist at Northwell Health, said he doesn't believe it's a good idea to recommend a second period of isolation, as some patients will still test positive on a rapid antigen test for more than two weeks after their diagnosis, despite research showing the majority of coronavirus transmissions occur within the first five days of infection.

"If you ask too much from your patients, there's a point where they say, 'You know what, that's unreasonable,' and they don't do anything," he said. "If we now start saying that everyone who has a couple more days of feeling crummy has to isolate again, it's going to be hard at this stage of the pandemic to get people not to just say, 'I'm not going to listen at all.'" (Gleeson, Becker's Hospital Review, 5/25; Weintraub, USA Today, 5/25; AHA News, 5/24; Bendix, NBC News, 5/24; Lazar, Boston Globe, 5/24)