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Longitudinal Patient-Reported Outcome Trajectories in Long COVID: Findings From the STOP-PASC Clinical Trial
Prasanna Jagannathan1, Haley Hedlin2, Jane W Liang2,3
1Department of Medicine, Stanford University School of Medicine, Stanford, California, USA.
Open Forum Infectious Diseases
|October 30, 2025
Summary
Long COVID patient symptom trajectories vary significantly. This study found no clear benefit of nirmatrelvir/ritonavir (NMV/r) across different symptom patterns, highlighting the need for Long COVID-specific outcome measures.
Area of Science:
- Post-infectious illness research
- Clinical trial analysis
- Patient-reported outcome measurement
Background:
- Long COVID is a complex condition with diverse symptoms.
- Existing patient-reported outcome (PRO) measures lack specific validation for Long COVID.
- A trial of nirmatrelvir/ritonavir (NMV/r) in Long COVID showed no overall treatment effect.
Purpose of the Study:
- To identify distinct symptom trajectories in Long COVID patients.
- To characterize clinical features associated with symptom improvement or worsening.
- To explore potential treatment effects in different symptom subgroups.
Main Methods:
- Latent class trajectory modeling (LCTM) was applied to PRO data from 155 randomized participants.
- PRO measures included Patient Global Impression of Severity (PGIS), Patient Global Impression of Change (PGIC), PROMIS domains, and core symptoms.
- Participants were followed for 15 weeks with serial symptom assessments.
Main Results:
- LCTM identified distinct symptom trajectories for PGIS, PGIC, PROMIS-Physical Function, and fatigue.
- Worsening symptom groups showed higher NMV/r treatment proportions, cardiovascular symptoms, and low-dose naltrexone use.
- Improving groups had shorter time since infection and better baseline physical function; no subgroup benefited from NMV/r.
Conclusions:
- Heterogeneous PRO trajectories reflect the clinical diversity of Long COVID.
- Nirmatrelvir/ritonavir (NMV/r) did not demonstrate clear benefits in any identified subgroup.
- Validated, Long COVID-specific PRO instruments and targeted trials for subtypes are crucial.
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