Pfizer’s Paxlovid Ineffective Against Long COVID Using 15-Day Regimen: Study

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Pictured: Entrance to Pfizer's office in Brussels, Belgium/iStock, Alexandros Michailidis

Pfizer’s oral antiviral Paxlovid (nirmatrelvir/ritonavir) does not appear to significantly ease symptoms in patients with long COVID, according a Phase II study from Stanford Medicine.

The results, published Friday in JAMA Internal Medicine, showed that at 10 weeks, Paxlovid did not significantly lower the severity of the six core symptoms of long COVID, compared with patients who were treated with placebo and ritonavir. These core symptoms include fatigue, brain fog, shortness of breath, body aches, gastrointestinal symptoms and cardiovascular symptoms.

Paxlovid was also unable to significantly differentiate itself from placebo in terms of fatigue, dyspnea, physical function and cognitive function. Patients hit comparable scores on the Patient Global Impression of Severity or Patient Global Impression of Change inventories, both of which are patient-reported scales that assess treatment effect.

The Pfizer-funded Phase II STOP-PASC trial is the first such test of Paxlovid treatment for long COVID, according to Stanford.

Despite showing no significant efficacy signals, the Paxlovid regimen—which included twice-daily treatment for 15 days—was found to be safe overall. Side effects were comparable between the active treatment and placebo groups, with mostly low-grade adverse events.

Upinder Singh, senior author and co-principal investigator, in a statement said that the lack of a clinical response observed in the study does not mean that no evidence of clinical benefit will be found in the future.

The study has not sufficiently addressed all uncertainties regarding the subject, Singh added. “Should we have tested patients with symptoms present after only seven or eight months instead of 16 or 17? Should we have treated them for a longer time? Were we even testing the right patients? Maybe only some symptoms will be responsive to antiviral treatment.”

Still, Singh and team were able to establish the safety of a prolonged Paxlovid regimen, which in the study was given for three times as long as the recommended dosing duration for acute COVID-19. This finding could have important implications for those who need longer antiviral exposures, “for example, in instances where a newly infected patient is immunocompromised,” Singh said.

Long COVID, known in scientific literature as the post-acute sequelae of SARS-CoV-2 infection, refers to a diverse group of COVID-19-related symptoms that arise at least three months after the initial infection. Around 10% to 20% of patients who had COVID-19 develop long COVID, which in the U.S. alone corresponds to tens of millions of people, according to Stanford Medicine.

However, the definition of long COVID remains ambiguous, with more than 200 symptoms potentially linked to the condition. The underlying disease mechanisms are also highly heterogeneous and difficult to elucidate, making drug development complicated. There are currently no FDA-approved treatments for long COVID.

Tristan Manalac is an independent science writer based in Metro Manila, Philippines. Reach out to him on LinkedIn or email him at or

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