President Joe Biden on Saturday tested positive for the coronavirus again after previously testing negative in a case of "viral rebound," which can sometimes occur after taking the antiviral Paxlovid.

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Biden experiences 'viral rebound,' tests positive for Covid-19 again

On July 21, the White House announced Biden had tested positive for Covid-19 and was experiencing "very mild symptoms." Biden began isolating at the White House and started taking Paxlovid, an antiviral developed by Pfizer that has been shown to reduce hospitalizations and death from Covid-19 by 90% among patients at risk of developing a severe case of the disease.

Then, on July 27, the White House announced that Biden had tested negative for Covid-19, which Biden said would allow him to "return to work in person."

However, on Saturday, July 30, Biden tested positive again, "after testing negative on Tuesday evening, Wednesday morning, and Friday morning," according to Biden's physician, Kevin O'Connor. He said the president's test "represents 'rebound' positivity."

On Twitter, Biden announced, "Folks, today I tested positive for COVID again. This happens with a small minority of folks. I've got no symptoms but I am going to isolate for the safety of everyone around me. I'm still at work, and will be back on the road soon."

Folks, today I tested positive for COVID again.

This happens with a small minority of folks.

I’ve got no symptoms but I am going to isolate for the safety of everyone around me.

I’m still at work, and will be back on the road soon.

— President Biden (@POTUS) July 30, 2022

"The president has experienced no reemergence of symptoms, and continues to feel quite well," O'Connor said. "This being the case, there is no reason to re-initiate treatment at this time, but we will obviously continue close observation." Biden will be returning to "strict isolation procedures," O'Connor added.

In a video, Biden said he's "going to be working from home for the next couple days" and added that he's "feeling fine, everything's good."

A quick update. pic.twitter.com/FgT1sGlZCY

— President Biden (@POTUS) July 30, 2022

What do experts know about viral rebound?

Biden's rebound case highlights a phenomenon that is still being researched. In May, CDC 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.

"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.

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." CDC also 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."

How frequently Covid-19 rebound occurs is still uncertain, experts say. "It remains one of the most confusing things I can recall during the pandemic," said Bob Wachter, chair of medicine at the University of California, San Francisco.

Pfizer has said just 2% of their unvaccinated, high-risk patients who took Paxlovid in clinical trials experienced Covid-19 rebound. A study of 483 patients conducted by the Mayo Clinic in June found a rebound rate of less than 1%, while another study from Case Western Reserve University and NIH found that 5.4% of patients who took Paxlovid tested positive again after 30 days and 5.9% experienced a rebound of symptoms.

In a tweet, White House Covid-19 response coordinator Ashish Jha said real-world data suggests that the rate of viral rebound after taking Paxlovid is between 0.5% and 10%. He added that he hasn't seen any data suggesting rebound rates are higher than 10%.

Experts are also uncertain about why Covid-19 rebound happens. Daniel Griffin, an infectious disease expert, said he thinks rebounding has nothing to do with Paxlovid. He said physicians have seen that, especially in high-risk patients, having Covid-19 usually includes two weeks of worsening symptoms. Griffin said he thinks Paxlovid may suppress the first half of those symptoms, and when it stops working, the rebound occurs.

John Moore, a virologist at Weill Cornell Medicine, said he hasn't heard "anyone come up with a definitive cause" of Covid-19 rebound, adding that he believes Biden is "just the unlucky guy in the one out of 20. It's just a numbers game."

As a result of the confusing data regarding viral rebounds, Wachter said prescribing Paxlovid for healthy, vaccinated patients is a "massively complicated three-dimensional chess game."

"I can barely decide whether I want it, and I do this for a living," he said. (Joseph, STAT News, 7/30; Vakil, The Hill, 7/30; Frieden, MedPage Today, 7/30; Baker/Weiland, New York Times, 7/31; Gutman-Wei, The Atlantic, 7/30)