Paxlovid May Reduce Risk of Long Covid in Eligible Patients, Study Finds

People who took the antiviral drug Paxlovid within a few days after being infected with the coronavirus were less likely to be experiencing long Covid several months later, a large new study found.

The findings suggest that for people who are medically eligible for the antiviral — older adults or people with certain health problems — Paxlovid not only reduces the odds that they will be hospitalized or die from a coronavirus infection, but also lowers their risk of long-term symptoms.

“The results are quite provocative and suggest that further investigation of antiviral agents and their effects on long Covid is urgently needed,” said Dr. Michael Peluso, an assistant professor of medicine at the University of California, San Francisco, who was not involved in the new research.

The study, which was published online without undergoing peer review, does not indicate whether antivirals might be beneficial for other patients, like younger people or those without high-risk medical conditions. And it does not give any inkling whether Paxlovid might be a treatment for long Covid itself, a question being investigated by other researchers.

The researchers analyzed the electronic medical records of 56,340 patients who had at least one risk factor for a severe response to coronavirus infection. They found that the 9,217 patients who took Paxlovid within five days of testing positive were 26 percent less likely to have a wide range of post-Covid symptoms about 90 days later than the 47,123 patients who received no antiviral or antibody treatment.

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The patients were part of the Veterans Health Administration system and tested positive for the coronavirus between March 1 and June 30 of this year, a period when Omicron variants were dominant. Those who took Paxlovid experienced reduced risk of long Covid regardless of vaccination status or whether they had been infected with the coronavirus previously, the study found.

The study authors and other medical experts said the findings provided additional motivation for medically eligible patients to take Paxlovid soon after becoming infected. Though Paxlovid has been proven effective in reducing hospitalizations and deaths in high-risk Covid patients, some people have become wary of the medication because a small percentage of patients experience “Paxlovid rebound” — a recurrence of Covid symptoms or positive test results. Several high-profile rebound cases, including President Biden and his top Covid adviser, Dr. Anthony Fauci, have added to the concern.

“For people who are already qualified for Paxlovid use, to me, really the choice is clear,” Dr. Ziyad Al-Aly, the senior author of the study, said. “Do you get a metallic taste, do you get side effects from Paxlovid, can you get rebound? Yes. But we have proven data suggesting that Paxlovid in the acute phase reduces the risk of severe illness, meaning the risk of death and hospitalization. And now we’re showing in the post-acute phase, there’s also risk reduction.”

Dr. Al-Aly and Dr. Peluso said many medically eligible patients were either not getting access to the drug or were declining it. “This study provides further evidence for treating people who have acute Covid with antivirals, especially if they have risk factors for severe outcomes,” Dr. Peluso said.

Most study participants were male, three-quarters were white, and their average age was about 65, so the findings may not apply to all patients. Still, Dr. Al-Aly said, regardless of race, sex, age or type of previous medical problem, “getting Paxlovid was actually better than not getting it in terms of reducing risk in the acute phase and reducing risk in the post-acute phase.”

One explanation for the findings, Dr. Peluso said, is related to the fact that people who become severely ill in the acute phase of infection are more prone to long-lasting symptoms or to developing new health issues weeks later. So, by helping patients avoid hospitalization and other serious initial consequences, Paxlovid could prevent some post-Covid symptoms “tied to the damage done in the first couple of weeks of infection,” he explained.

He added that another reason a beneficial effect on long Covid seemed logical is that “many of the risk factors for severe Covid are likely to overlap” with risk factors for long Covid. Still, many people who experience only mild symptoms in their initial infections develop long Covid, as do people who did not have previous risk factors.

Dr. Al-Aly said it’s possible that “giving your immune system a hand by suppressing that virus initially is really kind of like nipping it in the bud, producing a risk reduction for the acute stage and also in the post-acute phase.” That would support a theory that one cause of long Covid might be viral fragments persisting in the body, keeping the immune system activated.

For the study, Dr. Al-Aly, chief of research and development at the V.A. St. Louis Health Care System and a clinical epidemiologist at Washington University in St. Louis, and colleagues evaluated the records of veteran’s administration patients whose risk factors included being over 60, being overweight, smoking or having conditions like cancer, heart disease, hypertension or diabetes.

After about 90 days, patients who took Paxlovid — three pills twice a day for five days — were less likely to exhibit 10 out of 12 long Covid medical issues, including fatigue, shortness of breath, muscle pain, blood clotting problems, cardiovascular problems and neurocognitive impairments like brain fog. For unclear reasons, Dr. Al-Aly said, there was no significant difference between Paxlovid and non-Paxlovid patients for two post-Covid issues: new-onset diabetes and coughing.

Overall, for every 100 patients treated with Paxlovid, there were 2.3 fewer cases of long Covid, the study found.

Patients with the poorest health before their coronavirus infection — with more than five risk factors for experiencing serious Covid illness — experienced the greatest risk reduction for long Covid. Patients who had received booster doses of vaccines experienced lower risk reduction than those who were unvaccinated or vaccinated without boosters, probably, Dr. Al-Aly said, because boosters had already given them greater immune system protection.

Dr. Al-Aly said many additional questions about antivirals should be explored, such as whether taking Paxlovid for more days or in higher doses would further reduce risk for long Covid.

Dr. Peluso cautioned that in the study the treatment “did not completely eliminate post-Covid conditions” and said that at his hospital, “we have seen cases of people who develop long Covid despite antiviral treatment in early infection.”

So, he said, “much like vaccination, antiviral treatment during acute infection is likely to be one tool in the armamentarium to reduce the risk of post-Covid sequelae, but is unlikely to totally solve the problem.”