‘Paxlovid rebound’ raises questions about how long COVID antiviral treatment will last


President Biden testing positive for COVID-19 again days after completing a course of Paxlovid has raised questions about whether the duration of antiviral treatment should be reconsidered.

Just days after completing a five-day course of COVID-19 antiviral treatment from Pfizer, Biden’s doctor, Kevin O’Connor, said in a letter Saturday that the president had tested positive again. As of Wednesday, Biden still tested positive for COVID-19.

This phenomenon has become known as the “Paxlovid rebound”, when a person tests positive for the coronavirus again even after initially testing negative after a round of treatment with the antiviral. A recent pre-print study found that Paxlovid rebound occurred in 3.5% and 5.4% of coronavirus infections 7 days and 30 days after treatment, respectively. Biden’s chief medical adviser, Anthony Fauci, also experienced Paxlovid’s rebound after contracting the virus and began a second round of treatment.

Some experts have called for studies on extending Paxlovid treatments to be prioritized, as early research has suggested that Paxlovid rebound may occur due to insufficient exposure to the drug. Researchers at the University of California, San Diego School of Medicine said last month that the drug may not be reaching enough infected cells in the allotted time.

Paxlovid, under emergency use authorization issued by the Food and Drug Administration (FDA), is administered in two doses taken daily for five days. Physicians are not permitted to prescribe longer treatment cycles, and clinical data on cycles longer than five days is not yet complete.

Earlier this year, Fauci said the National Institutes of Health was in talks with Pfizer about studies looking at longer courses of Paxlovid, though no updates on those possible trials were released.

“I’m actually still flabbergasted that we haven’t set up a clinical trial to figure this out. It’s an easy thing to do,” Robert M. Wachter, director of the Department of Medicine at The Hill, told The Hill. the University of California at San Francisco.

“It wouldn’t cost that much to be able to rack up enough patients in a week or two and follow them for a few weeks so we could have an answer,” Wachter said, adding that the data needed to potentially extend the duration of a round of Paxlovid could have already been collected if the trials had started just a few months ago.

According to Wachter, there is no similar antiviral “analogies” to compare Paxlovid to. Viral rebound is generally not tested and other antiviral treatments are not given in the same way.

Eric Toner, senior fellow at the Johns Hopkins Center for Health Security at the Bloomberg School of Public Health, noted that viral rebound has rarely been studied as much as it is now in the context of COVID. However, Toner said cases of virus or bacterial infections persisted after treatment.

The viral rebound cases of the coronavirus are also not unique to Paxlovid. Rebound cases with molnupiravir, the COVID-19 antiviral created by Merck and Ridgeback, have also been seen.

People who experience antiviral rebound cases are still at risk of transmitting COVID-19 to others. Michael Charness, a researcher at the Veterans Administration Medical Center in Boston, recently told CNN that he and his colleagues have observed at least two cases of people infecting others after their symptoms reappear. Both cases involved people who tested positive again after taking Paxlovid.

People tend to have much milder symptoms that go away quite easily on their own after testing positive again, Toner said. For this reason, he said a second round of treatment, even if Paxlovid rebounds, is probably not necessary. O’Connor, Biden’s doctor, provided regular updates on the president’s health, but did not reveal whether he had started a second course of Paxlovid like Fauci has.

While the need for and feasibility of longer Paxlovid cycles remains unclear, the United States may find itself relying more on antivirals as new, more infectious and better able to evade protection, COVID-19 variants emerge. immune, continue to appear.

“If we see more variants and they’re more evasive and we have more people with infections that are at risk of having a serious outcome, then antivirals will become more and more important,” Wachter said, although that he added: “As far as we know, none of this is really true.

He noted that even with subvariants like BA.5 spreading and causing more infections, current vaccines still offer strong protection against severe cases, hospitalizations and deaths.

Researchers have previously said it would be difficult, but not impossible, for COVID-19 to become resistant to the Paxlovid treatment because the drug targets a part of the virus that does not easily change.

When reached for comment, a Pfizer spokesperson pointed to a Centers for Disease Control and Prevention (CDC) health advisory issued earlier this year that stated that a brief return of COVID-19 symptoms after completion of Paxlovid treatment “could be part of the natural history of SARS-CoV-2.

“Although further evaluation is warranted, we have not seen any viral resistance emerge to date in patients treated with PAXLOVID, and we continue to monitor data from our ongoing clinical studies and safety monitoring. post-clearance,” the spokesperson said. “We remain very confident in the clinical efficacy of PAXLOVID to prevent serious consequences of COVID-19 in patients at increased risk.”

The Pfizer spokesperson did not comment on the possibility of longer Paxlovid courses.


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