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Concerns about Paxlovid’s rebound prevent some doctors from prescribing the life-saving drug and some high-risk patients from taking it
Paxlovid gets bad press due to considerations about the COVID “rebound. “This is the main conclusion of a series of articles indicating that whether or not other people take the antiviral drug, many have symptoms that come and go before disappearing completely.
In recent months, several peer-reviewed, pre-printed studies evaluated COVID patients in placebo clinical trial teams for Paxlovid and other treatments. As part of the trials, patients on those teams had to have their symptoms monitored on a full daily basis. Researchers consistently found that up to 30% of those who hadn’t taken an antiviral experienced an increase in coughing, fatigue, headaches or other symptoms after feeling better.
The studies aim to address considerations about a phenomenon called Paxlovid rebound, which occurs when a user who has taken an antiviral such as Paxlovid (a mixture of nirmatrelvir and ritonavir tablets) reports a resurgence of symptoms or positive control after a negative control. a while after they stop taking the medicine. One of the first papers to describe the resurgence of COVID after an antiviral case study co-authored by Davey Smith, an infectious disease physician and researcher at the University of California, San Diego, and colleagues. However, Smith’s search soon returnedto hang out with him. As anecdotal reports of the phenomenon began to pile up last summer, reports that added high-profile instances like President Joe Biden and Anthony Fauci of the National Institutes of Health, public opinion of Paxlovid began to decline. The drug was once hailed as a savior for high-risk patients who were suddenly dismissed for not valuing it.
Despite Paxlovid’s proven effectiveness in preventing serious illness and death in other high-risk individuals, Smith has found that he develops resistance to this product. Says. Perhaps more troubling, however, is the fact that some doctors are reluctant to prescribe it. “The medication kept other people out of the hospital and prevented them from dying,” Smith says. Take it,” she adds, and “I felt guilty because I started it all. “
Because he knew that respiratory viral symptoms tend to come and go, regardless of the virus or treatment, Smith set out to better characterize the evolution of COVID itself. As chair of the U. S. government-sponsored ACTIV-2 trial. In the U. S. , a series of placebo-controlled studies that aim to compare new COVID remedies — he had a wealth of knowledge at his fingertips, so he dove into the trials and gave placebo teams extra scrutiny.
In one of the studies, published in JAMA Network Open last October, Smith and colleagues looked at an organization of subjects in the placebo organization in the ACTIV-2 trial and found that 30% experienced at least two symptom-free days. before one or more of your symptoms have returned. Of those who had this rebound in symptoms, at most all had mild to moderate symptoms and none required hospitalization. In another study, published as preprint and recently peer-reviewed, Smith et al. evaluated patients in the placebo setting for symptom rebound and viral load (the number of other people infected with the virus was increasing). deleting), as measured by PCR. check, the most delicate check for SARS-CoV-2 infection, the virus that causes COVID. The researchers found that 10% of their untreated subjects had symptoms recurring after their symptoms fully resolved, 27% saw their symptoms shortly before feeling worse again, and 12% had a detectable resurgence of the virus. the same. But a viral comeback rarely coincided with a worsening of symptoms: only 1-2% of the subjects tested experienced either.
Smith wasn’t surprised by the results. ” As an infectious disease physician, [I know] that respiratory disease viruses have this expansion and decline,” he says, adding that this also happens with colds, flu, and respiratory syncytial virus (RSV). It’s probably because most symptoms are similar to the body’s inflammatory reaction to the virus, not the virus itself, he says. He got rid of the body.
Other infectious disease specialists agree. ” In my opinion, the rebound story has been exaggerated,” says Ziyad Al-Aly, a clinical epidemiologist and head of studies and education at the Department of Veterans Affairs at the St. Health Care System. Louis. Il notes that he has heard of doctors who oppose prescribing Paxlovid to high-risk patients for fear of a rebound or the much-lamented side effect of a bitter, metallic taste. However, he says, “the rebound never killed anyone. ” But COVID can land you in the hospital or, worse, it can lead to your death.
Robert Wachter, chairman of the Department of Medicine at the University of California, San Francisco, heard similar reactions to Paxlovid. ,'” he says. ” I perceive it viscerally, but it doesn’t make sense when you take a look at an unbiased accounting sheet of the pros and cons of the drug. . . It’s not that close. “
Another benefit Wachter et al. point to is the potential for the drug to decrease the risk of long-lasting COVID, which can manifest as a wide variety of symptoms that persist for months or even years after the initial infection. According to a recent preliminary study by Al-Aly and colleagues, taking Paxlovid within the first five days after a positive test reduced the risk of prolonged COVID symptoms by an average of 26% in a high-risk patient population. “We started to think about why other people get COVID for a long time,” says Al-Aly. Some hypothesize that SARS-CoV-2 “remains in them in some form and leads to clinical manifestations of fatigue, brain fog, etc,” she says. So she wondered: was it imaginable that taking the antiviral early could prevent the virus from replicating and prevent it from running wild? The researchers looked at subjects from their high-risk population: those who smoked, had diabetes, were older than 60, or had other points known to predispose someone to severe COVID. They found that Paxlovid reduced the risk of developing 10 of the 12 prolonged COVID symptoms tested during the study.
So far, the U. S. Food and Drug Administration has been in the U. S. The U. S. Department of Health has only conditionally approved Paxlovid under an emergency use authorization for the remedy of high-risk patients. The option that it can lessen the threat of COVID in long-term COVID in low-risk patients is tempting, yet no one has been able to examine the intensity of the challenge because the drug has not been approved for this population. “This is what I call a domain without evidence,” Al-Aly says, and it’s a domain he and others have. asked Pfizer to investigate. Pfizer, which evolved and makes Paxlovid, dropped out of its study in low-risk patients when its data showed no difference in hospitalization and death in the short term. A study by researchers not affiliated with Pfizer found similar results. A Pfizer The spokesperson contacted by Scientific American had no further comment as the company continues to compare its data.
Until more knowledge emerges, doctors want to rely on their gut and any falsified information they can find. The existing knowledge constantly relates to the benefits of Paxlovid. ” says Wachter. I will definitely give it to other high-risk people. Most of my colleagues who have contracted COVID have taken it. And Wachter, who is 65, adds that if he tests positive for COVID, he will surely take the drug itself.
Doctors agree that COVID rebound after antivirals can be a nuisance, but it is much bigger than hospitalization or death. “Paxlovid is the most productive weapon we have now for other people with COVID,” says Smith, who knows the remedy landscape better than anyone else. It helps keep other people out of the hospital, prevents them from dying, and likely decreases the risk of prolonged COVID. In short, I think it’s worth the bitter taste.
Arab-American scientist
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