It’s well documented that Paxlovid – a 5-day course of antiviral pills from Pfizer – can reduce the risk of hospitalization in COVID-19 patients who are more likely to develop severe disease.
Now, researchers from the Veterans Health Administration are finding that taking the drug may also reduce the chances of later developing long COVID, according to a new study which went live this weekend and has yet to be peer reviewed.
“We have known for some time that Paxlovid reduces the risk of acute problems,” says Dr. Ziyad Al-Alychief of research and development at the VA Saint Louis Healthcare System, and co-author of the study, “We now add the observation that Paxlovid also reduces the risk of long-lasting COVID.”
The drug, which has been available in the United States for nearly a year, is provided free by the federal government to pharmacies across the country. It requires a prescription and patients with COVID-19 should start it within five days of the onset of symptoms.
Fewer viruses, less COVID?
In the study, long COVID was defined as developing one or more symptoms — including heart problems, blood disorders, fatigue and difficulty breathing — one to three months after testing positive. According to these measures, patients who took Paxlovid were 26% less likely to develop long COVID.
To arrive at this finding, the researchers combed through the electronic health records of more than 56,000 patients in the VA health system who tested positive for COVID-19 between March and June 2022, and had at least a risk factor for serious illness. They compared the health outcomes of 9,000 patients who had taken Paxlovid early in their illness, with 47,000 patients who had not taken it.
The benefits of taking Paxlovid didn’t just apply to those who weren’t vaccinated. Patients who were vaccinated or boosted, or who had repeated COVID-19 infections, had a similar reduction in risk of developing long COVID, the study found.
The study is a preprint, which means it was shared publicly before being reviewed and approved by external researchers. But experts who weren’t involved in the study tell NPR the results make sense, given how Paxlovid works.
The antiviral drug stops the virus from replicating in cells. “We know that one of the key factors predicting long COVID is detectable virus in the blood 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 that prevent the virus from reproducing further would therefore lead to a lower risk of long COVID.”
Previous studies have shown that Paxlovid reduces the risk of hospitalization and death from COVID-19. “Given that the trigger for Long COVID is acute SARS-CoV-2 infection, it makes intuitive sense that anything that reduces the severity of that infection will reduce the risk of Long COVID, whether Paxlovid or other antiviral treatments”, Dr Paul Saxinfectious 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 potential uses for Paxlovid. The VA study was observational, based on data captured from patients’ health records – according to Sax, “the imprecision of the [long COVID] diagnosis makes definitive conclusions from this study difficult, especially with a retrospective review.”
But the value of the study is that it points researchers to promising avenues for more research, says Dr Monica Gandhi, an infectious disease physician at UCSF. “It generates assumptions,” she says, “It’s exciting and hopeful [to think] only if you reduce the viral load… to undetectable [early in the illness]maybe you can prevent post-COVID symptoms altogether” – a theory she thinks researchers could pursue.
Sax and Gandhi both say they would feel more confident in the results if they were replicated in other studies, especially in experimental randomized controlled trials which compare long-term COVID outcomes in patients who took Paxlovid or a placebo. The results of the VA study are also limited by the fact that the participants were predominantly white men, raising the possibility that the benefits of Paxlovid may be different in other patient groups.
Currently, Paxlovid is only authorized for use in patients who have risk factors – such as being older or having underlying health conditions – that put them at high risk of developing serious disease. Al-Aly says the reduction in long-term COVID risk raised in his study suggests that others may also benefit from taking Paxlovid. But many patients who currently have long COVID were relatively young and healthy before contracting COVID-19 and may not have qualified for Paxlovid when they tested positive, he says.
“Does the use of Paxlovid in a low-risk population reduce the risk of acute problems and subsequently reduce the risk of prolonged COVID?” Al-Aly wonders: “I think this is a question that we all have to solve over the next few months.”
It’s also an open question whether a higher dose or longer treatment might provide greater benefit, Chin-Hong says.
Side effects which include nausea and an off-putting taste have made patients think about using the product. Reports of COVID rebound in Paxlovid patients, where the disease flares up after an apparent respite, have made some prescribers ambivalent about the product. These are real considerations, says Al-Aly, but they must be weighed against the benefits of Paxlovid treatment, including reduced risk of hospitalization and death in the acute phase, and the possibility of avoiding a long COVID in the following months.
Gandhi says the study results can now be factored into clinicians’ decisions, even though the results are preliminary and have not yet been replicated.
“This study pushes me to use [Paxlovid] in people over 65, vaccinated and boosted, as this will likely have benefits other than preventing hospitalization,” she says.