Paxlovid, the antiviral developed by Pfizer to reduce the risk of hospitalization in at-risk Covid-19 patients, may reduce the risk of patients developing long Covid, according to a new preprint study published in medRxiv.

Study details

For the study, researchers analyzed the medical records of 56,340 participants in the Department of Veterans Affairs' medical database who had at least one risk factor for severe Covid-19 and had tested positive for the coronavirus between March 1 and June 30.

Of the participants, 9,217 were given Paxlovid within five days of testing positive, while the remaining participants did not receive any antiviral or antibody treatment for Covid-19.

The researchers defined long Covid as a patient developing one or more symptoms one to three months after testing positive for the coronavirus. The researchers found that, among those who received no treatments at all, 9.43 per 100 persons reported developing long Covid 90 days after testing positive. Meanwhile, among those who received Paxlovid, 7.11 per 100 persons developed long Covid, representing a 26% risk reduction.

Participants in the study who had been vaccinated or boosted against Covid-19, or had repeat Covid-19 infections, had a similar reduction in their risk of developing long Covid after taking Paxlovid as those who were unvaccinated.

Reaction

Experts said the findings of the study make sense given the way Paxlovid works.

"We know that one of the key factors that predict long COVID is detectable virus in the bloodstream at the time of infection," said Peter Chin-Hong, an infectious disease physician at the University of California, San Francisco. "So it stands to reason that interventions that prevent the virus from making more copies of itself would therefore lead to a lower risk of long Covid."

"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," said Paul Sax, an infectious disease physician at Brigham and Women's Hospital.

However, Sax cautioned that the study was observational and based on data entered into patient health records, meaning "the imprecision of the [long COVID] diagnosis makes definitive conclusions from this study challenging, especially with a retrospective view."

Akiko Iwasaki, a professor of immunobiology and molecular, cellular, and developmental biology at Yale University, said the study is "very important" and "has public health implications that are quite relevant today."

Iwasaki suggested that using Paxlovid to stop the coronavirus from replicating might prevent not just viral persistence but other mechanisms of the virus by restricting it to the upper respiratory tract before it migrates elsewhere in the body.

"The virus is the trigger for all of the other hypotheses," Iwasaki said. "Nip it in the bud as quickly as possible, and some of these things could be prevented."

Eric Topol, a professor of medicine and EVP of Scripps Research, said the study is "a major advance."

"We have no treatment that has been validated to treat Long Covid," he said. "Rigorous, randomized, definitive clinical trials are long overdue."

Ziyad Al-Aly, chief of research and development at the VA Saint Louis Healthcare System and co-author of the study, said the results suggest that patients other than the ones Paxlovid is currently authorized for may benefit from the medication.

"Does Paxlovid use in a lower-risk population reduce the risk of acute problems and subsequently reduce the risk of long Covid?" he said. "I think that's a question that we all need to solve over the next several months."

However, David Putrino, director of rehabilitation innovation at Mount Sinai Health System, cautioned that it's possible the study's results could be related to Paxlovid's ability to reduce the severity of Covid-19 that can lead to lingering complications.

"Many, many others with long covid had mild/non-hospitalized acute disease but went on to develop this debilitating, syndromic, ME/CFS-type long covid," Putrino said.

Similarly, Benjamin Abramoff, director of the Post-COVID Assessment and Recovery Clinic at Penn Medicine, cautioned the study findings could be the result of underlying differences unaccounted for in the study, including the potential that one group may be more engaged with their physicians than the other.

"The study provides more evidence for the importance of prospective controlled studies to look into Paxlovid as a means of preventing long Covid in the broader population," he said.

For its part, Pfizer said it is "working with multiple institutions toward the start of studies to evaluate Paxlovid for potential use in addressing long covid." (Huang, "Shots," NPR, 11/8; Choi, The Hill, 11/7; Sellers, Washington Post, 11/7; Belluck, New York Times, 11/7; Carbajal, Becker's Hospital Review, 11/7)