Extended Paxlovid treatment fails to ease long COVID symptoms in 959-person trial

A clinical trial published in The Lancet Infectious Diseases on August 31, 2026, reveals that extended treatment with the antiviral drug Paxlovid does not ease long COVID symptoms compared to a placebo. The RECOVER-VITAL trial evaluated 959 adult patients across 69 U.S. sites to test if targeting lingering SARS-CoV-2 could alleviate chronic symptoms. Although the extended 25-day regimen proved safe with no serious side effects, it failed to show clinical benefits for cognitive, autonomic, or exercise-related symptoms.

RECOVER-VITAL Paxlovid trial results

• ▪The RECOVER-VITAL clinical trial studied 959 adult patients with long COVID across 69 sites in the United States, collecting data between July 2023 and early 2025.
• ▪Co-principal investigator Lindsey Baden, MD, of Mass General Brigham stated that treating viral persistence with the antiviral medication Paxlovid did not show evidence of clinical benefit in the RECOVER-VITAL trial.
• ▪Participants in the RECOVER-VITAL trial were randomly assigned to either 25 days of Paxlovid, 15 days of Paxlovid plus 10 days of ritonavir and a placebo, or 25 days of ritonavir and a placebo.
• ▪A clinical trial published in The Lancet Infectious Diseases on August 31, 2026, showed that the antiviral drug Paxlovid does not improve long COVID symptoms compared to a placebo.

Viral persistence hypothesis

• ▪Researchers designed the RECOVER-VITAL trial to test whether Paxlovid could reduce long COVID symptoms by targeting SARS-CoV-2 virus that may still linger in the body.
• ▪While Paxlovid is typically prescribed for five days to stop viral replication during acute COVID-19, the RECOVER-VITAL trial tested extended regimens to target hypothesized viral persistence.

Long COVID symptom classification

• ▪The RECOVER-VITAL trial categorized its 959 participants into three symptom groups of approximately 320 people each: cognitive dysfunction, autonomic dysfunction, and exercise intolerance or post-exertional malaise.
• ▪Long COVID is defined as a chronic health condition occurring after a SARS-CoV-2 infection that lasts for at least three months.

Extended Paxlovid safety profile

• ▪Study researchers monitored the safety and effectiveness of the extended Paxlovid regimens using lab tests, in-clinic visits, and periodic participant symptom ratings over a six-month period.
• ▪The RECOVER-VITAL trial demonstrated that extending the duration of Paxlovid treatment up to 25 days did not cause serious side effects for participants.

RECOVER Initiative research network

• ▪The National Institutes of Health's RECOVER Clinical Trials program includes seven additional studies exploring potential treatments for symptoms affecting the quality of life of long COVID patients.
• ▪The RECOVER-VITAL trial is part of the National Institutes of Health's Researching COVID to Enhance Recovery Initiative, a patient-centered research network designed to study and treat long COVID.
• ▪The RECOVER-VITAL trial protocol was designed with feedback and advice from a group of patient, caregiver, and community representatives.

1 source