Taking Paxlovid for up to 25 days did not ease Long COVID symptoms any better than a placebo did. The finding comes from the RECOVER-VITAL trial, run by the National Institutes of Health as part of its RECOVER initiative, and it closes off one of the most closely watched treatment ideas for people whose illness lingers months or years after infection.
The antiviral, whose active ingredients are nirmatrelvir and ritonavir, is normally prescribed for five days during acute infection. Researchers wanted to know whether a much longer course could clear out leftover virus that might be driving persistent symptoms. Across every group tested, the answer was no.
What the RECOVER-VITAL trial tested
The trial enrolled 959 adults with Long COVID at 69 sites across the United States, with data collected from July 2023 to March 2025. Its full title describes it as a randomised, double-blind, placebo-controlled, phase 2 trial, a design that keeps both participants and clinicians from knowing who received the active drug. The work was funded through NIH’s RECOVER Initiative and the National Heart, Lung, and Blood Institute.
Volunteers were sorted into three groups by their main complaint: trouble thinking clearly, trouble regulating blood pressure or heart rate, and an inability to tolerate exercise. Grouping by dominant symptom mattered because Long COVID is not one condition with one presentation, and a drug that helped only one cluster could have been missed in a single pooled analysis. Within each symptom group, participants were randomly assigned to one of three regimens, every one lasting 25 days. One arm received Paxlovid throughout. A second received Paxlovid for the first 15 days, then ritonavir with a placebo pill standing in for nirmatrelvir for the last 10. The third received ritonavir plus the placebo pill from the start.
No edge over placebo, in any symptom group
Participants rated their symptoms over six months, with in-clinic visits, laboratory tests and remote check-ins supplementing those ratings. According to the NIH summary, the antiviral “didn’t improve any of the three groups’ Long COVID symptoms compared with placebo.” Symptoms got better at the same rate regardless of which regimen a person had been given. That symmetry is the core of the result. Had the longer course worked, the full 25-day arm should have pulled ahead of the 15-day arm and of the placebo arm. It did not. Improvement appeared in all three arms equally, which points to the natural fluctuation of the illness, or to the attention and monitoring of trial participation, rather than to anything the drug did.
The authors note that the outcome fits with smaller earlier studies, which had found no benefit from a 15-day antiviral course. The NIH write-up describes the longer 25-day treatment as well tolerated, with hardly any serious side effects, so the negative result is not explained by participants dropping out because of harm. The drug was safe enough to give; it simply did not help.
What the researchers say they gained
Dr. Lindsey Baden of Mass General Brigham, who co-led the study with Dr. Kanecia Zimmerman of Duke Medical Center, pointed to a different kind of return from a negative result. Baden said the team learned how to better characterize and measure the symptoms that patients with Long COVID are suffering from. Building sturdier symptom measures is a practical gain, since later trials of other drugs will need reliable ways to tell real improvement from noise, and the three-group structure of RECOVER-VITAL gave the team a chance to test measures separately for thinking problems, circulatory problems and exercise intolerance.
The results were published in Lancet Infectious Diseases, listed ahead of print on Aug. 31, 2026, and NIH summarized them in a Sept. 29, 2026 Research Matters article by Christine Lehmann. The study team is still analyzing blood samples to look for signs of persistent virus and for markers of how individuals responded to treatment, and it plans to release further results.
Where Long COVID research goes next
For patients, the trial removes a tempting option rather than adding one. The Centers for Disease Control and Prevention’s Long COVID overview describes the condition as a wide range of ongoing health problems. A condition that broad can have more than one driver, so a single negative antiviral trial leaves the other explanations open. A negative trial of this size still has value, because it stops clinicians and patients from pursuing a prolonged course with no demonstrated payoff.
NIH has been publishing work that points toward other explanations. Its Research Matters series has covered findings that the immune system may attack the nervous system in some Long COVID patients, that a cold virus may set the stage for Long COVID, and that Long COVID symptoms are linked to inflammation. None of those leads has produced a proven treatment, but each suggests mechanisms beyond lingering virus.
The pending blood analyses, which the study team has said it will report, from RECOVER-VITAL will test the viral-persistence idea more directly than symptom scores can. If they show little virus in participants, that would explain why an antiviral failed. If they show some, researchers will have to ask whether the drug missed it or whether it matters. Either way, the symptom result stands: 25 days of Paxlovid performed no better than placebo.
This article was produced with the assistance of AI and reviewed by Morning Overview editors prior to publication.
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