President Joe Biden has tested positive again for COVID-19, the latest and most prominent example of what doctors call “Paxlovid rebound.”
When Biden tested positive for COVID-19 earlier this month, doctors immediately prescribed Paxlovid, an anti-viral drug that can prevent severe illness in higher-risk patients.
Last week, Biden, 79, tested negative for the virus after finishing the prescribed five-day course of Paxlovid. But doctors were watching closely for signs of a “rebound” — a positive test, a recurrence, or even a worsening of COVID symptoms that some patients have experienced after taking the drug.
Biden has experienced “no reemergence of symptoms, and continues to feel quite well.
“However, given his positive antigen test, he will reinitiate strict isolation procedures,” Dr. Kevin O’Connor, the president’s physician, wrote in a Saturday memo. (See story, Page D9.)
Medical experts in New Hampshire say cases of COVID rebound after treatment with Paxlovid are happening here, but they stress that the drug has proven remarkably effective in preventing the worst complications of COVID-19 — hospitalizations and death.
Dr. Rebecca Wang, an infectious disease physician at Dartmouth Hitchcock Medical Center, said Paxlovid works.
“Never really in recent history for a respiratory virus can I think of an anti-viral medication being as effective, demonstrated in scientific literature, as what Paxlovid has shown,” she said.
One study of high-risk, unvaccinated patients showed an 89% reduction in hospitalizations and death from COVID, Wang said. As a result, “I really would say it has become the standard, when someone’s diagnosed with COVID, to at least assess 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 non-hospitalized adults with COVID-19.
Under the FDA emergency authorization for the drug, Wang said, patients need to have at least one risk factor for severe disease, but the Centers for Disease Control and Prevention lists a broad range of risk categories. That includes serious medical conditions such as cancer, chronic lung, kidney or liver disease and heart conditions, but it also includes pregnancy, mental health conditions and being overweight with a body mass index of 25 or higher.
“When you look at the American population, probably more people would qualify for Paxlovid than those who wouldn’t,” Wang said.
Throughout the pandemic, Wang has developed COVID protocols for Dartmouth Hitchcock, which have had to be continually revised as the pandemic has gone on, she said. For instance, monoclonal antibodies have proven unsuccessful against some of the new variants of the virus.
But Paxlovid, which blocks viral replication, has proven effective against all known variants, Wang said. That’s why, she said, “I’m optimistic these new antiviral medications will be less prone to having issues with emerging variants.”
Even when patients do rebound, their symptoms typically are mild, Wang said.
How it works
Dr. Jonathan Ballard, chief medical officer at 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 to be a two-part disease, Ballard said. “First it’s the spread of the virus in the body, the replication,” he said. But the secondary part, which is more dangerous, is “the immune system component, the inflammation, the swelling of lungs, that causes a lot of the really bad outcomes,” 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 with some people experiencing Paxlovid rebound, the treatment is still recommended for anyone at a higher risk, Ballard said. “So even if you do test positive again or have some rebound symptoms, you’re decreasing your risk of having an overwhelming, large immune effect,” he said.
“I would imagine if the president’s physician believes it important enough for him to take it, I think it’s probably also important enough for anyone else who has those risk factors in New Hampshire,” Ballard said.
One theory about the cause of the rebound some patients experience is that even after five days of the medication, a small amount of virus might remain that could be capable of replicating, Wang said. Then, “Once you take the anti-viral drug away, it does start to replicate and cause patients to develop symptoms,” she said.
That’s also what happened last month to Dr. Anthony Fauci, who told reporters that days after he finished treatment with Paxlovid, he tested positive again and experienced worse symptoms. But the 81-year-old director of the National Institute of Allergy and Infectious Disease also credited the drug with keeping him out of the hospital.
Paxlovid isn’t perfect
It’s not that Paxlovid is making people sick or causing the virus to become resistant, Wang said.
“It is theoretically possible that simply with the number of days you’re getting, it might not be fully suppressing the virus or the potential it can start to replicate again after you stop,” she said. “I don’t think it’s crazy to think maybe in 6 to 12 months, the course that’s recommended by national authorities might change.”
There has been some discussion about whether a second course of medication is warranted in rebound cases, Wang said, or whether a longer course of Paxlovid might prevent a recurrence of symptoms. Earlier this year, Pfizer, the company that makes Paxlovid, suggested that a longer course of the medication might be beneficial, she said, but “the FDA countered that.”
When researchers went back to the original Paxlovid study, they found that 1% to 2% of the subjects had experienced a rebound after taking the drug, Wang said. But she said, “In real life, that number does seem to be higher.”
“Part of the challenge is that the population that Paxlovid was studied in was in patients who were unvaccinated who had never had COVID before,” Wang said. “The number of people who fit that criteria is shrinking.”
So, does taking Paxlovid potentially lengthen the amount of time you have to isolate, staying home from work and avoiding at-risk 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’s no right or wrong answer,” she said. “As with many aspects of medicine, there’s no one-size-fits-all.”
Patients with liver or kidney conditions have to take a lower dose of Paxlovid. Young, healthy individuals who are vaccinated and boosted and who have only mild COVID-19 symptoms might choose not to take the medication, Wang said.
Anticipating a surge
Ballard from DHHS said Paxlovid is an important part of the state’s strategy in this third year of the pandemic.
“We do expect a fall/winter surge when people have to go back indoors more and have more potential spread of the disease, whether or not we have additional variants,’’ he said. “We’re planning under that assumption.”
DHHS has worked with the federal government and with major pharmacy chains to make sure that Paxlovid is widely available, Ballard said.
“Our goal this year is now with therapeutics and increased testing, that will decrease the severity of the impacts on our hospital system,” he said. “That’s what we will be looking at closely, our hospitalization numbers.”
As part of the state’s strategy, pharmacists in New Hampshire soon will be able to dispense the medication.
The Food and Drug Administration earlier this month revised its emergency use authorization for Paxlovid to allow licensed pharmacists to dispense Paxlovid. In response, New Hampshire’s Board of Pharmacy recently sent a notification to all licensed pharmacists.
“New Hampshire licensed pharmacists may dispense Paxlovid pursuant to a standing order issued by a New Hampshire licensed health care professional who is authorized to prescribe such medication for the treatment of COVID-19,” the board said.
“All (pharmacy) chains have medical directors, and we’re working with those medical directors trying to figure out how this new development with direct Paxlovid dispensing may work out,” Ballard said.
DHHS also is working on ways to make the drug available to vulnerable populations, such as those who are homebound or who lack transportation, Ballard said.
“The overall goal is to make sure it’s really readily 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 primary care provider whenever you test positive,” Ballard said. For those without a regular doctor, urgent care clinics are a good option, he said.
The medication is most effective when taken within five days of symptom onset, Wang said. “You do have the clock ticking,” she said.
Is there any evidence that Paxlovid could prevent long-term effects of COVID?
Another million-dollar question, Wang said. “It’s going to be at some point in the future an important part of this risk/benefit discussion,” she said. “We don’t have any answers at this point in time.”
“The coronavirus is still novel and these therapies are even more novel,” Wang said.
“I think it’s hard to be patient and be told, ‘Be patient, you’ll get more information soon,’ but I think that is the reality of the situation right now,” she said.