Longer Paxlovid Course Did Not Ease Long COVID, NIH Trial Finds
Extended courses of the antiviral Paxlovid did not improve long COVID symptoms compared with placebo, according to results from the NIH-funded RECOVER-VITAL trial released on August 31.
The paper was published in The Lancet Infectious Diseases and announced by Brigham and Women's Hospital. Its release says the phase 2 study was randomized, double-blind and placebo-controlled, recruited 959 adults with long COVID at 69 sites across the United States, and collected data between July 2023 and early 2025.
Paxlovid combines two drugs, nirmatrelvir and ritonavir, and is usually taken for five days to treat mild-to-moderate COVID-19. RECOVER-VITAL tested whether a longer course could ease long COVID symptoms by acting on the virus that may still be lingering in the body.
Participants were first grouped by their main symptom: trouble thinking clearly, known as brain fog; autonomic problems such as dizziness, fast heart rate or blood pressure changes; and exercise intolerance or post-exertional malaise, meaning exhaustion that interferes with daily activities. About 320 people were in each symptom group, the release says. Within those groups, participants were randomly assigned to 25 days of Paxlovid, to 15 days of Paxlovid followed by 10 days of ritonavir with a placebo standing in for nirmatrelvir, or to 25 days of ritonavir with that placebo.
Symptoms were tracked over six months through lab tests, clinic visits and participants' own periodic symptom ratings. Brigham and Women's Hospital says the longer course did not cause serious side effects.
"Unfortunately treating viral persistence with this antiviral medication did not show evidence of clinical benefit," said Lindsey Baden of Mass General Brigham, a co-principal investigator on the trial. Baden also said the study "contributes important findings to the science of studying Long COVID and viral persistence."
NIH funded the work through its RECOVER Initiative. Pfizer donated the study medication and joined design discussions but, the release says, did not take part in running the study, interpreting the data or writing the first draft of the manuscript. RECOVER lists seven additional trials of possible long COVID treatments.
