President Joe Biden has tested positive again for COVID-19, the latest and most prominent example of what doctors are calling a “Paxlovid rebound.”
When Biden tested positive for COVID-19 earlier this month, doctors immediately prescribed Paxlovid, an antiviral drug that can prevent serious illness in higher-risk patients.
Last week, Biden, 79, tested negative for the virus after completing the mandatory five-day Paxlovid course. But doctors closely watched for signs of a “rebound” — a positive test, recurrence, or even worsening of COVID symptoms that some patients have been experiencing after taking the drug.
Biden has “ experienced no recurrence of symptoms and remains feeling reasonably well.
“However, given his positive antigen test, he will resume strict isolation procedures,” wrote Dr. Kevin O’Connor, the president’s doctor, in a memo on Saturday. (See story, page D9.)
Medical experts in New Hampshire say it’s seeing cases of COVID rebound after treatment with Paxlovid, but stress that the drug has been shown to be remarkably effective at preventing the worst complications of COVID-19 — hospitalization and death .
dr Rebecca Wang, an infectious diseases doctor at Dartmouth Hitchcock Medical Center, said Paxlovid is working.
“Never in the recent history of a respiratory virus can I imagine an antiviral drug being as effective as what has been demonstrated in the scientific literature as what Paxlovid has shown,” she said.
A study of unvaccinated high-risk patients showed an 89 percent reduction in hospitalizations and deaths from COVID, Wang said. As a result, “I would really say that when someone is diagnosed with COVID, it has become the standard to at least evaluate them to see if they would be a potential candidate for Paxlovid,” she said.
The National Institutes of Health treatment guidelines for COVID-19 list Paxlovid as the preferred therapy for nonhospitalized adults with COVID-19.
As part of the drug’s FDA emergency approval, Wang said patients must have at least one risk factor for serious disease, but the Centers for Disease Control and Prevention lists a wide range of risk categories. These include serious illnesses such as cancer, chronic lung, kidney or liver disease and heart disease, but also pregnancy, mental illness and being overweight with a body mass index of 25 or higher.
“If you look at the American population, probably more people would qualify for Paxlovid than those who wouldn’t,” Wang said.
During the pandemic, Wang has been developing COVID protocols for Dartmouth Hitchcock that have had to be constantly revised as the pandemic has unfolded, she said. For example, monoclonal antibodies against some of the new variants of the virus have proved unsuccessful.
But Paxlovid, which blocks viral replication, has been shown to be effective against all known variants, Wang said. For that reason, she said, “I’m optimistic that these new antiviral drugs will be less prone to problems with emerging variants.”
Even when patients recover, their symptoms are usually mild, Wang said.
How it works
dr Jonathan Ballard, chief medical officer in the state Department of Health and Human Services, said medical science knows a lot more about the coronavirus that causes COVID-19 than it did two years ago.
It’s now understood that it’s a two-part disease, Ballard said. “First of all, it’s the spread of the virus in the body, the replication,” he said. But the secondary part that’s more dangerous is “that component of the immune system, the inflammation, the swelling of the lungs, that’s causing a lot of the really bad results,” he said.
“So the way Paxlovid works is trying to slow down the replication of the virus so your body doesn’t have this overwhelming immune response,” he said.
That’s why, even for some people who experience a Paxlovid rebound, treatment is still recommended for those at higher risk, Ballard said. “So even if you test positive again or have some rebound symptoms, you reduce your risk of having an overwhelming, large immune effect,” he said.
“I would imagine that if the president’s doctor thinks it’s important enough for him to take it, I think it’s probably important enough for anyone else who has these risk factors in New Hampshire, too,” Ballard said.
One theory about the cause of the rebound some patients experience is that even after five days of medication, a small amount of virus could remain that could replicate, Wang said. Then: “As soon as you take the antiviral drug away, it begins to replicate and causes patients to develop symptoms,” she said.
The same thing happened last month with Dr. Anthony Fauci, who told reporters he tested positive again days after completing treatment with Paxlovid and had worse symptoms. But the 81-year-old director of the National Institute of Allergy and Infectious Diseases also credited the drug with keeping him out of the hospital.
Paxlovid is not perfect
It’s not that Paxlovid makes people sick or makes the virus resistant, Wang said.
“It’s theoretically possible that simply with the number of days you get it may not completely suppress the virus or the potential for it to be able to replicate again after you stop,” she said. “I don’t think it’s crazy to think that maybe the course recommended by national authorities could change in 6 to 12 months.”
There has been some debate as to whether a second medication is warranted in rebound cases, Wang said, or whether prolonged treatment with Paxlovid might prevent symptoms from recurring. Earlier this year, Pfizer, the company that makes Paxlovid, suggested that taking the drug longer might be beneficial, she said, but “the FDA disagreed.”
When researchers went back to the original Paxlovid study, they found that 1 to 2 percent of subjects experienced a rebound after taking the drug, Wang said. But she said, “In real life, that number appears to be higher.”
“Part of the challenge is that the population in which Paxlovid was studied was of unvaccinated patients who had never had COVID before,” Wang said. “The number of people who meet these criteria is shrinking.”
So is taking Paxlovid potentially increasing the time you have to isolate, stay home from work and avoid vulnerable relatives?
“That’s the million-dollar question,” Wang said.
This is where “shared decision-making” between medical providers and their patients is key, she said. “There is no right or wrong answer,” she said. “As with many aspects of medicine, there is no magic formula.”
Patients with liver or kidney disease need to take a lower dose of Paxlovid. Young, healthy individuals who are vaccinated and refreshed and have only mild COVID-19 symptoms may choose not to take the drug, Wang said.
In anticipation of an increase
DHHS’ Ballard said Paxlovid is an important part of the state’s strategy in this third year of the pandemic.
“We expect a spike in the fall/winter when people need to return indoors more and have more potential spread of the disease, whether or not we have additional variants,” he said. “We plan under this assumption.”
DHHS has been working with the federal government and with major pharmacy chains to ensure Paxlovid is widely available, Ballard said.
“Our goal this year is now for therapeutics and increased testing that will reduce the severity of the impact on our hospital system,” he said. “That’s what we’re going to look at closely, our hospitalization numbers.”
As part of the state’s strategy, pharmacists in New Hampshire will soon be able to dispense the drug.
The Food and Drug Administration revised its emergency use authorization for Paxlovid earlier this month to allow licensed pharmacists to dispense Paxlovid. In response, the New Hampshire Board of Pharmacy recently sent out a notice to all licensed pharmacists.
“Licensed pharmacists in New Hampshire may dispense Paxlovid pursuant to a standing order issued by a New Hampshire licensed healthcare professional authorized to prescribe such drugs to treat COVID-19,” the board said.
“All (pharmacy) chains have medical directors and we are working with those medical directors to see how this new development with direct delivery of Paxlovid might work,” Ballard said.
DHHS is also working on ways to make the drug available to vulnerable populations, such as B. for those who are housebound or lack transportation, Ballard said.
“The overall goal is to make sure it really is easily accessible to anyone who needs it,” he said.
Timing is important
Experts say it’s best to start taking Paxlovid as soon as possible after testing positive for COVID-19.
“The message is to call your GP if you test positive,” Ballard said. For those without a regular doctor, emergency clinics are a good option, he said.
The drug is most effective when taken within five days of the onset of symptoms, Wang said. “You make the clock tick,” she said.
Is there any evidence that Paxlovid could prevent the long-term effects of COVID?
Another million-dollar question, Wang said. “At some point in the future, it’s going to be an important part of that risk-benefit discussion,” she said. “We have no answers at this time.”
“Coronavirus is still new, and these therapies are even more novel,” Wang said.
“I think it’s hard to be patient and to be told, ‘Be patient, you’ll have more information soon’, but I think that’s the reality of the situation right now,” she said.