Longitudinal Patient-Reported Outcome Trajectories in Long COVID: Findings From the STOP-PASC Clinical Trial
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By
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Prasanna Jagannathan
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Haley Hedlin
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Jane W Liang
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Blake Shaw
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Evan Maestri
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Michelle Lin
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P J Utz
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Upinder Singh
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Linda N Geng
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Hector Bonilla
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October 8, 2025
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Clinical Scorecard: Exploring Patient-Reported Outcome Patterns in Long COVID: Insights from the STOP-PASC Clinical Trial
At a Glance
| Category | Detail |
|---|
| Condition | Long COVID, a heterogeneous post-infectious chronic condition following SARS-CoV-2 infection |
| Key Mechanisms | Potential viral or viral particle persistence; multi-system symptom heterogeneity including fatigue, brain fog, dyspnea, cardiovascular symptoms |
| Target Population | Adults with Long COVID symptoms persisting at least 3 months post SARS-CoV-2 infection |
| Care Setting | Clinical trial setting evaluating therapeutic interventions for Long COVID |
Key Highlights
- STOP-PASC trial showed no overall benefit of nirmatrelvir/ritonavir (NMV/r) in Long COVID symptom improvement
- Latent class trajectory modeling identified distinct symptom trajectory subgroups reflecting clinical heterogeneity
- Existing patient-reported outcome (PRO) instruments lack validation and specificity for Long COVID, limiting diagnostic and therapeutic monitoring
Guideline-Based Recommendations
Diagnosis
- Long COVID diagnosis based on persistent symptoms ≥3 months post-infection affecting one or more organ systems
- Use of PRO measures such as PGIS, PGIC, and PROMIS domains for symptom assessment, acknowledging lack of Long COVID-specific validation
Management
- No demonstrated efficacy of nirmatrelvir/ritonavir for Long COVID symptom improvement in this trial
- Need for targeted therapeutic trials tailored to Long COVID subtypes identified by symptom trajectory patterns
Monitoring & Follow-up
- Serial symptom assessments using PRO instruments over time to capture symptom trajectories
- Consideration of heterogeneity in symptom patterns for individualized monitoring
Risks
- Potential cardiovascular symptom prevalence in worsening symptom subgroups
- Use of low-dose naltrexone noted in worsening symptom groups, requiring further evaluation
Patient & Prescribing Data
155 adults with Long COVID randomized 2:1 to NMV/r or placebo
No clear subgroup demonstrated benefit from NMV/r; worsening symptom groups had higher NMV/r treatment proportion
Clinical Best Practices
- Recognize Long COVID as a heterogeneous condition requiring individualized assessment
- Employ longitudinal PRO measures to identify symptom trajectory subgroups
- Develop and validate Long COVID-specific PRO instruments for improved diagnosis and therapeutic monitoring
- Design targeted therapeutic trials based on identified Long COVID subtypes and symptom trajectories
References
