Paxlovid doesn’t lower long COVID risk, more patients report ‘rebound’

SAN FRANCISCO — Paxlovid, the first oral antiviral drug for treating COVID-19 among adults, does not appear to help reduce the risk of developing “long COVID” for vaccinated, non-hospitalized individuals dealing with their first infection. New research from the University of California San Francisco Medical Center also shows that more people are seeing a rebound effect after taking the drug than had been previously reported.

Paxlovid (Nirmatrelvir-ritonavir) treatment for COVID has shown considerable effectiveness among high-risk unvaccinated individuals. However, the influence of the drug on long COVID risk, such as whether it protects vaccinated people from having symptoms for an extended period of time, has remained largely a mystery.

So, study authors gathered together a group of vaccinated people who reported their first positive test for COVID-19 between March and August of 2022 and avoided hospitalization. Some participants reported using oral Paxlovid treatment during the acute phase of their COVID infection, while others didn’t use the drug. In December 2022, everyone also answered a round of follow-up questions focusing on long COVID, COVID rebound symptoms, and how long each person continued to test positive.

Notably, researchers say the two groups were actually quite similar; roughly 16 percent of those given Paxlovid had long COVID symptoms, and 14 percent of those not treated with the medication also developed long COVID issues. Typical symptoms included fatigue, shortness of breath, confusion, headache, and altered taste and smell. Importantly people who took Paxlovid and then went on to develop long COVID still reported just as many long COVID symptoms as others not treated with Paxlovid.

A small percentage of people developed severe long COVID. Once again, those who took Paxlovid were just as likely to have severe long COVID symptoms as those who did not.

Among those who saw symptomatic improvement during Paxlovid treatment, a total of 21 percent reported rebound symptoms. Of that group, 10.8 percent reported one or more long COVID symptom in comparison to 8.3 percent without rebound symptoms. For those who repeated antigen testing after testing negative and completing treatment, a notably high 25.7 percent reported rebound test positivity. All in all, 26.1 percent reported either rebound symptoms or test positivity.

“We found a higher proportion with clinical rebound than previously reported but did not identify an effect of post-treatment rebound on long COVID symptoms,” says study first author Dr. Matthew Durstenfeld, a cardiologist and UCSF assistant professor of Medicine, in a media release. “Our finding that Paxlovid treatment during acute infection is not associated with lower odds of long COVID surprised us, but it is consistent with two other rigorously conducted studies finding no difference in post-COVID conditions between 4 and 6 months after infection.”

Rresearchers stress this project likely had certain limitations associated with its observational nature; study authors relied on patient self-reporting of treatment and long COVID symptoms.

The study is published in the Journal of Medical Virology.