WASHINGTON (AP) — President Joe Biden tested positive for COVID-19 again Saturday, slightly more than three days after he was cleared to exit coronavirus isolation, the White House said, in a rare case of “rebound” following treatment with an anti-viral drug.

White House physician Dr. Kevin O’Connor said in a letter that Biden “has experienced no reemergence of symptoms, and continues to feel quite well.”

In accordance with Centers for Disease Control and Prevention guidelines, Biden will reenter isolation for at least five full days. The agency says most rebound cases remain mild and that severe disease during that period has not been reported.

Word of Biden’s positive test came — he had been negative Friday morning — just two hours after the White House announced a presidential visit to Michigan this coming Tuesday to highlight the passage of a bill to promote domestic high-tech manufacturing. Biden had also been scheduled to visit his home in Wilmington, Delaware, on Sunday morning, where first lady Jill Biden has been staying while the president was positive. Both trips have been canceled as Biden has returned to isolation.

Biden, 79, was treated with the anti-viral drug Paxlovid, and tested negative for the virus on Tuesday and Wednesday. He was then cleared to leave isolation while wearing a mask indoors. His positive tests puts him among the minority of those prescribed the drug to experience a rebound case of the virus.

Both the Food and Drug Administration and Pfizer point out that 1% to 2% of people in Pfizer’s original study on Paxlovid saw their virus levels rebound after 10 days. The rate was about the same among people taking the drug or dummy pills, “so it is unclear at this point that this is related to drug treatment,” according to the FDA.

While Biden was testing negative, he returned to holding in-person indoor events and meetings with staff at the White House and was wearing a mask, in accordance with CDC guidelines. But the president removed his mask indoors when delivering remarks on Thursday and during a meeting with CEOs on the White House complex.

Asked why Biden appeared to be breaching CDC protocols, press secretary Karine Jean-Pierre said, “They were socially distanced. They were far enough apart. So we made it safe for them to be together, to be on that stage.”

Regulators are still studying the prevalence and virulence of rebound cases, but the CDC in May warned doctors that it has been reported to occur within two days to eight days after initially testing negative for the virus.

“Limited information currently available from case reports suggests that persons treated with Paxlovid who experience COVID-19 rebound have had mild illness; there are no reports of severe disease,” the agency said at the time.

When Biden was initially released from isolation on Wednesday, O’Connor said the president would “increase his testing cadence” to catch any potential rebound of the virus.

Patients should re-isolate for at least 5 days. Per CDC guidance, they can end their re-isolation period after 5 full days if fever has resolved for 24 hours (without the use of fever-reducing medication) and symptoms are improving. The patient should wear a mask for a total of 10 days after rebound symptoms started.”

Paxlovid has been proven to significantly reduce severe disease and death among those most vulnerable to COVID-19. U.S. health officials have encouraged those who test positive to consult their doctors or pharmacists to see if they should be prescribed the treatment, despite the rebound risk.

Biden is fully vaccinated, after getting two doses of the Pfizer coronavirus vaccine shortly before taking office, a first booster shot in September and an additional dose March 30.

While patients who have recovered from earlier variants of COVID-19 have tended to have high levels of immunity to future reinfection for 90 days, Jha said that the BA.5 subvariant that infected Biden has proven to be more “immune-evasive.”

“We have seen lots of people get reinfected within 90 days,” he said, adding that officials don’t yet have data on how long those who have recovered from the BA.5 strain have protection from reinfection.