Paxlovid has come under fire over concerns about the “rebound” of COVID. This is the main takeaway from a series of papers showing that many people’s symptoms wax and wane before completely disappearing, whether or not people are taking antiviral medications.
Over the past few months, a number of peer-reviewed and preprint studies have investigated COVID patients in the placebo arms of clinical trials of paxlovid and other treatments. As part of the trial, patients in these groups were required to complete a daily symptom tracker. Researchers consistently found that 30% of those who didn’t take antivirals experienced a rebound of coughing, fatigue, headaches, or other symptoms after initially feeling better. Did.
These studies have shown that people who took antiviral drugs such as paxlovid (a combination of nilmatrelvir and ritonavir tablets) experienced a relapse of symptoms or a positive result after stopping the drug and having an immediate negative result. It is intended to address concerns about a phenomenon called Pax Lovid’s rebound that occurs when experiencing I am taking medication. His one of the first papers describing his COVID resurgence after administration of antiviral drugs was co-authored by his Davey Smith, an infectious disease specialist and researcher at the University of California, San Diego, and his colleagues. It’s a case study. But it didn’t take long before Smith’s research came back to haunt him. As anecdotal reports about the phenomenon began to pile up last summer, with reports including high-profile cases involving the likes of President Joe Biden and Anthony Fauci of the National Institutes of Health, public opinion against Pax Lovid began to decline. Once hailed as a savior for high-risk patients, the drug was abruptly dismissed as not worth the effort.
Despite paxlobid’s proven effectiveness in preventing serious illness and death in people considered at high risk, Smith found a growing resistance to paxlobid. “When Pax Lovid’s rebound started to pick up steam, he was, frankly, kind of annoyed,” he says. But perhaps more worrying is the fact that some doctors have become reluctant to prescribe it. increase. “My patients started saying they didn’t want to take it,” he adds.
Knowing that symptoms of respiratory viruses tend to come and go, regardless of the virus or treatment, Smith set out to better characterize the course of COVID itself. As chairman of his U.S. government-sponsored ACTIV-2 trial (a series of placebo-controlled studies aimed at evaluating new his COVID treatments), he had a ton of data at hand, so the trial and gave the placebo group extra information. scrutiny.
In one of the studies published in JAMA network open Last October, Smith and his colleagues examined a group of placebo subjects in the ACTIV-2 trial and found that 30% were symptom-free for at least two days before one or more symptoms returned. I found Of those who had recurrences of this condition, almost all had mild to moderate symptoms and none required hospitalization. They evaluated both symptom rebound and viral load (the amount of virus shed by infected people) in patients in the placebo group, measured by a PCR test. A sensitive test for infection by SARS-CoV-2, the virus that causes COVID. The researchers found that 10% of untreated subjects had symptoms that recurred after symptoms had completely resolved, 27% had some improvement and then worsened again, and 12% had no detectable virus itself. found that there was a recurrence of However, viral relapses rarely coincided with worsening symptoms, with only 1-2% of subjects experiencing both.
Smith was not surprised by this result. “As an infectious disease doctor, [I] We know that respiratory disease viruses often cycle this cycle,” he said, adding that it also happens with colds, flu and respiratory syncytial virus (RSV). “It’s just their nature.” This is most likely related to the body’s inflammatory response to the virus rather than the virus itself, he says. It lasts longer and fades as viral debris is cleared from the body.
Other infectious disease experts agree. “In my view, the rebound story has been exaggerated,” says Ziyad Al-Aly, a clinical epidemiologist and director of research and education services for the VA St. Louis Health Care System. He often hears of doctors resisting prescribing paxlovid to high-risk patients for fear of the many deplorable side effects of rebound and a bitter, metallic taste. . But COVID can lead to hospitalization and, worse, death. ”
Robert Wachter, medical director at the University of California, San Francisco, has heard similar reactions to Paxlovid. ’ he says. “I get it instinctively, but it doesn’t make sense when you look at the sober ledger of the drug’s benefits and drawbacks..It’s not a very close call.”
Another benefit Wachter and colleagues point to is the drug’s potential to reduce long-term COVID risk. COVID can cause a range of symptoms that last for months or years after initial infection. A recent preprint study by Al-Aly and his colleagues found that taking Paxlovid during his first five days after a positive test reduced his risk of long-term COVID symptoms to an average in a high-risk patient population. decreased by 26%. “We started thinking about why people are taking his COVID so long,” he says Al-Aly. There is also a hypothesis that SARS-CoV-2 “somehow stays in the body and causes clinical symptoms such as fatigue and brain fog”. I thought it might be possible to stop it and prevent it from going out of control. The researchers looked at subjects from a high-risk population who smoked, had diabetes, were over the age of 60, or had other factors known to predispose someone to severe his COVID. . They found that paxlovid reduced the risk of developing 10 of the 12 long-term COVID symptoms the study looked at.
So far, the U.S. Food and Drug Administration has only conditionally approved paxlobid under an Emergency Use Authorization to treat high-risk patients. The possibility is intriguing, but the drug is not approved for that population, so we have not been able to study the issue in detail. It’s a thing,’ says Al-Aly, where he and others have asked Pfizer to investigate. Pfizer, which develops and manufactures paxlovid, abandoned studies in low-risk patients after data showed no difference between hospitalization and death in the short term. A study by researchers unrelated to Pfizer found similar results.Pfizer spokesperson contacted Scientific American did not comment beyond the company’s continued evaluation of the data.
Until more data emerges, doctors must rely on their intuition and the hard information they can find. Existing data consistently show benefits of Paxlovid. “In my world, people look at the data and believe that the benefits of medication are pretty likely,” he says Wachter. “We’re going to give it to high-risk people. Most of my colleagues who have COVID are taking it.” And his 65-year-old Wachter has tested positive for COVID. Adds that if you absolutely take the medicine yourself.
Doctors agree that COVID rebounds after antiviral drugs may be a nuisance, but are far better than hospitalizations and deaths. It’s the best weapon,” says Smith, who knows the treatment situation better than anyone. “It will keep people out of hospitals, prevent deaths, and possibly reduce the risk of prolonging COVID.
