President Joe Biden tested positive for COVID-19 on Thursday and is experiencing “very mild symptoms,” underscoring the persistence of the highly contagious virus as new variants challenge the nation’s efforts to resume normalcy after two and a half years of pandemic disruptions.

White House Press Secretary Karine Jean-Pierre said Biden has begun taking Paxlovid, an antiviral drug designed to reduce the severity of the disease.

She said Biden has “very mild symptoms” and “will isolate at the White House while continuing to carry out all of his duties fully.” She said Biden has been in contact with members of the White House staff by phone and will participate in his planned meetings at the White House “via phone and Zoom from the residence.”

Biden, 79, 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.

Jean-Pierre said Biden had last tested negative on Tuesday, and he will stay isolated until he tests negative again. Biden had planned to visit Pennsylvania on Thursday to talk about his crime prevention plans and attend a Democratic fundraiser, and then spend a long weekend in Delaware. Those events are canceled.

First lady Jill Biden spoke to reporters as she arrived at a school in Detroit on Thursday, telling them she had just gotten off the phone with her husband.

“He’s doing fine,” she said. “He’s feeling good.”

The first lady, who was wearing a mask, said she tested negative earlier in the day.

Up to this point, Biden’s ability to avoid the virus seemed to defy the odds, even with the testing procedures in place for those expected to be in close contact with him. Prior waves of the virus swept through Washington’s political class, infecting Vice President Kamala Harris, Cabinet members, White House staffers and lawmakers. Biden has increasingly stepped up his travel schedule and resumed holding large indoor events where not everyone is tested.

Top White House officials in recent months have been matter-of-fact about the likelihood of the president getting COVID, a measure of how engrained the virus has become in society — and of its diminished threat for those who are up to date on their vaccinations and with access to treatments.

When administered within five days of symptoms appearing, Paxlovid, produced by drugmaker Pfizer, has been proven to bring about a 90% reduction in hospitalizations and deaths among patients most likely to get severe disease.

In an April 30 speech to more than 2,600 attendees at the White House Correspondents’ Association dinner, Biden acknowledged the risks of attending large events, but said it was worthwhile to attend.

“I know there are questions about whether we should gather here tonight because of COVID,” he said. “Well, we’re here to show the country that we’re getting through this pandemic.”

Biden is far from the first world leader — and not the first U.S. president — to get the coronavirus, which has infected British Prime Minister Boris Johnson, French President Emmanuel Macron and more than a dozen other leaders and high-ranking officials globally.

When Biden’s predecessor, President Donald Trump, contracted the disease in October 2020, it was a far different time. Vaccines were not available and treatment options were limited and less advanced. After being diagnosed with COVID-19 at the White House, Trump was given an experimental antibody treatment and steroids after his blood oxygen levels fell dangerously low. He was hospitalized at Walter Reed National Military Medical Center for three days

While much of the world has resumed normal rhythms after the early lockdowns to control spikes in cases and deaths, the virus still serves as a disrupter in daily life as people are forced to change plans, isolate and calculate the risks of taking part in various activities.

And after more than two years and over a million deaths in the U.S., the virus is still killing an average of 353 people a day in the U.S., according to the Centers for Disease Control and Prevention. The unvaccinated are at far greater risk, more than two times more likely to test positive and nine times more likely to die from the virus than those who have received at least a primary dose of the vaccines, according to the public health agency.

The White House has faced a flurry of questions about COVID-19 protocols surrounding the president. The spring Washington outbreak came weeks after the Centers for Disease Control and Prevention eased face-covering guidance in most of the U.S.

As the virus crept closer to Biden, then-White House press secretary Jen Psaki said Biden believed it to be “vitally important to him, to his presidency, to the American people,” to travel and continue to host large events.

She added of Biden, “Just like many Americans, he makes risk assessments.”

The highly transmissible omicron variant is the dominant strain in the U.S., but scientists say it poses a lower risk for severe illness to those who are up to date on their vaccinations. The BA.5 sub-strain, believed to be even more contagious, now makes up more than 65% of U.S. cases.

“There’s a lot of infections across America,” White House COVID-19 coordinator Dr. Ashish Jha said May 18, blaming the highly-transmissible variants, as well as relaxing mitigation measures like mask requirements.

The coronavirus pandemic helped put Biden in the White House, as he pledged to handle COVID-19 better than his predecessor. After initial months of success surging the nation’s supply and availability of vaccines, the virus became a morass for the Democrat in the first year of his presidency, as he struggled to boost the country’s vaccination rate and to stay ahead of the unpredictable disease.

As cases sharply declined earlier this year, Biden again highlighted his administration’s efforts to end the pandemic and help the nation regain a sense of normalcy.

In his State of the Union address on March 1, Biden said it was safe for most Americans to resume their normal pre-pandemic activities, citing declining case rates, vaccinations and newly developed therapeutics.

“Tonight, I can say we are moving forward safely, back to more normal routines,” he said. “It’s time for Americans to get back to work and fill our great downtowns again.”

Yet in recent weeks, U.S. officials have called for the public to exercise caution once again over the BA.5 variant, and appealed to the public to seek out booster shots if eligible and for most Americans to consider whether they should wear a face mask in public indoor settings.

“We should not let it disrupt our lives,” Dr. Anthony Fauci, the nation’s top infectious disease expert said July 12, “but we cannot deny that it is a reality that we need to deal with.”

The White House has sought to go above and beyond public health guidelines to protect the president, with all visitors and staff, required to attest to their vaccination status or submit to daily tests. Additionally, people expected to be in close proximity to Biden are tested daily.

Still, Biden has increasingly demonstrated a willingness to participate in larger, indoor events in recent months — riskier activities for contracting the virus — and many have had people not wearing masks. White House officials say Biden was intent on showing he can fulfill his presidential responsibilities without fear of the virus, believing he was well protected against severe outcomes

“His doctors are comfortable that he could continue to carry out his duties because of all these steps and precautions and protections he’s taken,” Psaki said on April 8.

In studies, the vaccines most widely used in the U.S. have been found to protect against severe illness and hospitalization, but new cases have emerged even among those who are fully vaccinated.