Clinical Report: Patient-Reported Outcome Patterns in Long COVID from STOP-PASC Trial

Overview

The STOP-PASC trial explored symptom trajectories in Long COVID patients treated with nirmatrelvir/ritonavir (NMV/r) versus placebo. Distinct patient-reported outcome (PRO) trajectories revealed heterogeneity in symptom progression, with no clear benefit of NMV/r across subgroups. Improving symptom groups had shorter time since infection and better baseline physical function.

Background

Long COVID is a chronic, heterogeneous condition following SARS-CoV-2 infection, affecting multiple organ systems and causing symptoms such as fatigue, brain fog, and dyspnea. Patient-reported outcome measures (PROs) adapted from other chronic illnesses have not been validated specifically for Long COVID, limiting diagnostic and therapeutic monitoring. The STOP-PASC randomized controlled trial tested NMV/r treatment in Long COVID but found no overall treatment effect. This exploratory analysis aimed to identify distinct symptom trajectories and clinical characteristics associated with improvement or worsening over time.

Data Highlights

Key Findings

• Latent class trajectory modeling identified distinct symptom trajectory groups in Long COVID patients across multiple PRO measures.
• Two PGIS groups emerged: a small improving group (n=17) and a large persistent/severe group (n=136).
• PGIC analysis revealed mostly improving patients (n=130) but a worsening subgroup (n=22) with higher NMV/r treatment and cardiovascular symptoms.
• Improving groups had shorter duration since initial infection and better baseline physical function scores.
• No subgroup demonstrated a clear therapeutic benefit from NMV/r treatment.
• Worsening groups had higher prevalence of cardiovascular symptoms and use of low-dose naltrexone.

Clinical Implications

These findings highlight the clinical heterogeneity of Long COVID and the limitations of current PRO instruments not specifically validated for this condition. Clinicians should recognize variable symptom trajectories and consider that NMV/r may not provide benefit in established Long COVID. There is a critical need for Long COVID-specific validated PRO tools and targeted therapeutic trials tailored to distinct patient subtypes.

Conclusion

Distinct patient-reported outcome trajectories underscore the heterogeneity of Long COVID and the absence of clear NMV/r treatment benefit. Future research should focus on validating Long COVID-specific PRO instruments and developing subtype-targeted therapies.

References

1. Peluso et al. 2024 -- Exploring Patient-Reported Outcome Patterns in Long COVID: Insights from the STOP-PASC Clinical Trial