Paxlovid, a 5-day course of antiviral medicines from Pfizer, has been shown to minimize the risk of hospitalization among COVID-19 individuals who are more susceptible to developing severe disease.
According to a recent study published online this weekend and not yet peer-reviewed by the Veterans Health Administration, taking the medicine may also lessen the risks of later developing lengthy COVID.
“We’ve already known for some time now that Paxlovid reduces the risk of acute problems,” says Dr. Ziyad Al-Aly, chief of research and development at the VA Saint Louis Healthcare System and co-author of the study, “Now we are adding the observation that Paxlovid also reduces the risk of long COVID.”
The drug, which has been available in the U.S. for almost a year, is provided for free by the federal government at pharmacies across the country. It requires a prescription, and patients with COVID-19 must start it within five days of symptoms onset.
Less virus, shorter COVID?
Long COVID was defined in the study as acquiring one or more symptoms, such as heart problems, blood abnormalities, exhaustion, and difficulty breathing, one to three months after testing positive. According to these criteria, patients who received Paxlovid were 26% less likely to acquire lengthy COVID.
To arrive at this conclusion, the researchers reviewed electronic health records from around 56,000 VA patients who tested positive for COVID-19 between March and June 2022 and had at least one risk factor for severe disease. They compared the health outcomes of 9,000 patients who took Paxlovid early in their disease to 47,000 patients who did not.
The benefits of taking Paxlovid didn’t just apply to those who were unvaccinated. The study found that patients who were vaccinated or boosted or had repeat COVID-19 infections had a similar reduction in the risk of developing long COVID.
The study is a preprint, meaning it was shared publicly before being reviewed and vetted by outside researchers. But experts who were not involved in the study tell NPR the findings make sense, given how Paxlovid works.
The antiviral drug stops the virus from replicating in cells. “We know that one of the key factors that predict long COVID is detectable virus in the bloodstream at the time of infection,” Dr. Peter Chin-Hong, an infectious disease physician at the University of California, San Francisco, wrote in an email. “So it stands to reason that interventions preventing the virus from making more copies of itself would lead to a lower risk of long COVID.”
Past studies have shown that Paxlovid reduces the risks of hospitalization and death from COVID-19. “Since the trigger of long COVID is acute infection with SARS-CoV-2, it makes intuitive sense that anything that lowers the severity of this infection would reduce the risk of long COVID, whether it’s Paxlovid or other antiviral treatments,” Dr. Paul Sax, an infectious disease physician at Brigham and Women’s Hospital in Boston, wrote in an email.
A starting point
Still, experts view the study as only a starting point for exploring the potential uses of Paxlovid. The VA study was observational, based on data entered into patient health records – in Sax’s view, “the imprecision of the [long COVID] diagnosis makes definitive conclusions from this study challenging, especially with a retrospective review.”
But the value of the study is that it points researchers down promising pathways for more research, says Dr. Monica Gandhi, an infectious disease physician at UCSF. “It’s hypothesis-generating,” she says, “It’s exciting and hopeful [to think] that if you reduce the viral load… down to undetectable [early in the illness], maybe you can prevent post-COVID symptoms” altogether – a theory she thinks researchers could pursue.
Both Sax and Gandhi say they would feel more confident in the results if they were replicated in additional studies, especially in experimental, randomized controlled trials that compare long COVID outcomes in patients who took either Paxlovid or a placebo. The VA study’s findings are also limited by the fact that the participants were predominantly white men, raising the possibility that the benefits of Paxlovid could be different in other groups of patients.
Paxlovid is only authorized for use in patients with risk factors – like being older or having underlying health conditions – that put them at high risk of developing severe disease. Al-Aly says the reduction in long COVID risk, raised in his study, suggests others might benefit from taking Paxlovid, too. But he says many patients who currently have long COVID were relatively young and healthy before they got COVID-19 and may not have qualified for Paxlovid when they tested positive.
“Does Paxlovid use in a lower-risk population reduce the risk of acute problems and reduce the risk of long COVID?” Al-Aly wonders, “I think that’s a question that we all need to solve over the next several months.”
It’s also an open question whether a higher dose or a longer treatment course could provide a greater benefit, Chin-Hong says.
Side effects, including nausea and an off-putting taste, have given patients pause about using the product. Reports of COVID rebound in Paxlovid patients, where the illness flares up after a seeming respite, has made some prescribers ambivalent about the product. These are real considerations, Al-Aly says, but they should be weighed against the benefits of Paxlovid treatment, including reduced risks of hospitalization and death in the acute phase, and the potential for avoiding long COVID in the months after.
Gandhi says the study’s findings may now factor into clinicians’ decisions, even if the results are preliminary and have not yet been replicated.
“This study is pushing me to use [Paxlovid] in people over 65, vaccinated and boosted, because it’s probably going to have other benefits beyond preventing hospitalization,” she says.
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