• Welcome to Phoenix Rising!

    Created in 2008, Phoenix Rising is the largest and oldest forum dedicated to furthering the understanding of, and finding treatments for, complex chronic illnesses such as chronic fatigue syndrome (ME/CFS), fibromyalgia, long COVID, postural orthostatic tachycardia syndrome (POTS), mast cell activation syndrome (MCAS), and allied diseases.

    To become a member, simply click the Register button at the top right.

Nirmatrelvir-Ritonavir and Symptoms in Adults With Postacute Sequelae of SARS-CoV-2 InfectionThe STOP-PASC Randomized Clinical Trial


Senior Member
Key Points
Question What is the efficacy of 15 days of nirmatrelvir-ritonavir for improving select symptoms of postacute sequelae of SARS-CoV-2 infection (PASC)?

Findings This randomized clinical trial including 155 participants with PASC symptoms (≥3 months’ duration) found that a 15-day course of nirmatrelvir-ritonavir in a mostly vaccinated study cohort was generally safe, but did not show significant benefit in improving fatigue, brain fog, body aches, cardiovascular symptoms, shortness of breath, or gastrointestinal symptoms.

Meaning These findings indicate that further studies are needed to determine the role of antivirals in the treatment of PASC.


Importance There is an urgent need to identify treatments for postacute sequelae of SARS-CoV-2 infection (PASC).

Objective To assess the efficacy of a 15-day course of nirmatrelvir-ritonavir in reducing the severity of select PASC symptoms.

Design, Setting, and Participants This was a 15-week blinded, placebo-controlled, randomized clinical trial conducted from November 2022 to September 2023 at Stanford University (California). The participants were adults with moderate to severe PASC symptoms of 3 months or longer duration.

Interventions Participants were randomized 2:1 to treatment with oral nirmatrelvir-ritonavir (NMV/r, 300 mg and 100 mg) or with placebo-ritonavir (PBO/r) twice daily for 15 days.

Main Outcomes and Measures Primary outcome was a pooled severity of 6 PASC symptoms (fatigue, brain fog, shortness of breath, body aches, gastrointestinal symptoms, and cardiovascular symptoms) based on a Likert scale score at 10 weeks. Secondary outcomes included symptom severity at different time points, symptom burden and relief, patient global measures, Patient-Reported Outcomes Measurement Information System (PROMIS) measures, orthostatic vital signs, and sit-to-stand test change from baseline.

Results Of the 155 participants (median [IQR] age, 43 [34-54] years; 92 [59%] females), 102 were randomized to the NMV/r group and 53 to the PBO/r group. Nearly all participants (n = 153) had received the primary series for COVID-19 vaccination. Mean (SD) time between index SARS-CoV-2 infection and randomization was 17.5 (9.1) months. There was no statistically significant difference in the model-derived severity outcome pooled across the 6 core symptoms at 10 weeks between the NMV/r and PBO/r groups. No statistically significant between-group differences were found at 10 weeks in the Patient Global Impression of Severity or Patient Global Impression of Change scores, summative symptom scores, and change from baseline to 10 weeks in PROMIS fatigue, dyspnea, cognitive function, and physical function measures. Adverse event rates were similar in NMV/r and PBO/r groups and mostly of low grade.

Conclusions and Relevance The results of this randomized clinical trial showed that a 15-day course of NMV/r in a population of patients with PASC was generally safe but did not demonstrate a significant benefit for improving select PASC symptoms in a mostly vaccinated cohort with protracted symptom duration. Further studies are needed to determine the role of antivirals in the treatment of PASC.

Trial Registration ClinicalTrials.gov Identifier: NCT05576662


Senior Member
United Kingdom
Interestingly it did work for a small subset of patients. So it's working for some of the phenotyped subsets. Of course the study doesn't check that so we haven't a clue which phenotype it worked on.


Senior Member
United Kingdom
Hi guys,

Am attaching the HD screenshots here:

Screenshot 2024-06-11 at 18.34.04.png

all the symptoms machine learned - showing distinctive clusters C 1 to 16.

16 endotypes were found, that's 16 subsets. Very close to Dr Goldstein's 16 drug testable subsets.

Screenshot 2024-06-11 at 18.34.13.png

Stratification by gender. Topic's correlate with biomarkers if I remember right.

Screenshot 2024-06-11 at 18.34.24.png

Then specific symptoms correlate with specific clusters. Left not normalised right normalised. Even with normalisation still specific subsets popping out, with more patients in the study maybe these would be darker across the board.

Screenshot 2024-06-11 at 18.36.47.png

Harder to read but it's a radial graph based on symptoms. LIke I did not have a cough, but I had acute tonsillitis, throat infection, shoulder and bone pain, neutropenia and elevated crp on diagnostic blood test day 6. I also had trouble breathing and terrible glass like pain in my lungs. at 5 months my hands feet and back started to play up.

But you can see here clear groupings which is the really interesting thing. David Putrino explains why that's important in the polybio symposium call (it's on youtube) use the index in the description it's 5 hours long.

(Summary below to go with the above slides)

Screenshot 2024-06-11 at 18.37.57.png


Senior Member
Participants were randomized 2:1 to treatment with oral nirmatrelvir-ritonavir (NMV/r, 300 mg and 100 mg) or with placebo-ritonavir (PBO/r) twice daily for 15 days.

How about a real placebo group, rather than a 'placebo' group that was still taking an antiviral. I really dislike this type of 'placebo' control where the placebo is an active treatment and often not clearly stated.