A large NIH-funded clinical trial has found that Paxlovid, the antiviral combination of nirmatrelvir and ritonavir commonly used to treat acute COVID-19, did not improve Long COVID symptoms when compared with placebo. The findings, published in the Lancet Infectious Diseases, add new evidence to a field still searching for effective treatments for the chronic condition that can follow SARS-CoV-2 infection.
What the study examined
The trial, known as RECOVER-VITAL Viral Persistence (PAXLOVID), was designed to test whether the antiviral could help patients whose symptoms may be driven by lingering viral persistence. Researchers enrolled 959 adults with Long COVID from 69 sites across the United States and collected data between July 2023 and early 2025.
Participants were first grouped by their main symptom profile: cognitive dysfunction, autonomic dysfunction, or exercise intolerance/post-exertional malaise. They were then assigned by chance to one of three treatment regimens: 25 days of Paxlovid, 15 days of Paxlovid plus 10 days of ritonavir and a placebo for nirmatrelvir, or 25 days of ritonavir plus a placebo for nirmatrelvir.
No clear benefit over placebo
Across the six-month follow-up period, participants reported their symptoms alongside lab tests and in-clinic visits. According to the study summary, Paxlovid did not appear to improve Long COVID symptoms compared with placebo. The trial did, however, show that the longer treatment duration did not cause serious side effects for participants.
“This study contributes important findings to the science of studying Long COVID and viral persistence,” Lindsey Baden of Mass General Brigham said in a statement included with the report. “Unfortunately treating viral persistence with this antiviral medication did not show evidence of clinical benefit.”
Why the result matters for Long COVID research
Long COVID is described in the report as a chronic health condition that can last for at least three months after a SARS-CoV-2 infection. The RECOVER initiative was created to understand, diagnose, prevent and treat the condition, and the latest findings narrow one possible treatment path that researchers had hoped might help.
The study also involved Patient, Caregiver, and Community Representatives in designing the protocol, and the broader RECOVER clinical trial program continues to test other possible treatments. For researchers and clinicians, the result is a reminder that not every antiviral approach aimed at viral persistence will translate into symptom relief for patients.
Read more in the original report from News Medical and the published trial in Lancet Infectious Diseases.
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