From Inflammation to Remodelling Towards Personalized Diagnosis in Post-acute Sequelae of COVID-19

Not yet recruiting

• Conditions: PASC Post Acute Sequelae of COVID 19; Long COVID; PASC; FAP; Fibroblast Activation Protein Inhibitor; Fibroblast; Long Covid-19; FAPI; Restrictive Lung Disease

• Registration Number: NCT06911476
• Lead Sponsor: University Medical Center Groningen

Brief Summary

Rationale: The diagnosis and pathogenesis of long COVID remains unknown. We have previously shown that \[68Ga\]FAPI Positron Emission Tomography-Computed Tomography (PET/CT) imaging shows potential for diagnosis and molecular understanding of this syndrome. We have previously shown that fibroblast activation protein (FAP) can be imaged in the lung, muscle and nasopharynx of long COVID patients (with dyspnea and fatigue). However, these preliminary data are derived from a selective group of patients with long COVID after critical COVID-19. We aim to explore the generalizability of these findings in patients with long COVID with dyspnea and fatigue, irrespective of the severity of their acute SARS-CoV-2 infection.

Primary objective: To assess if pulmonary fibroblast activity, measured by \[68Ga\]FAPI-46 PET/CT, is higher in patients with current long COVID dyspnea and fatigue compared to patients with resolved complaints.

Study design: This is a ZonMw funded single centre prospective observational cohort study of long COVID-19 patients with dyspnea and fatigue.

Study population: We will recruit 60 adult long COVID patients (aged \>20 years) of which 30 have complaints of dyspnea and fatigue and compare them to 30 patients with resolved complaints and healthy controls.

Main study parameters/endpoints: The primary endpoint is FAP expression in the lung measured by \[68Ga\]FAPI-46 PET/CT. Secondary endpoints are the expression of FAP in other tissues (muscle) and the relation between FAP and inflammation and remodelling biomarkers in various biological samples (e.g. serum/nasal epithelium).

Study procedures: In a single visit day the following data and samples will be collected: questionnaires, a lung function test, 6-minute walking test, blood samples, nose swabs, \[68Ga\]FAPI PET/CT scan and HRCT scan. When increased \[68Ga\]FAPI uptake is measured in the muscles a muscle biopsy will be performed as well.

Detailed Description

Not available

Study Timeline

• Status Verified: 2025-04
• Study First Submitted: 2025-04-01
• Study First Submitted QC: 2025-04-03
• Last Update Submitted: 2025-04-03
• Study First Posted: 2025-04-04
• Last Update Posted: 2025-04-04
• Study Start: 2025-05
• Primary Completion: 2025-12
• Study Completion: 2025-12

Recruitment & Eligibility

• Status: NOT_YET_RECRUITING
• Sex: All
• Target Recruitment: 60

Inclusion Criteria

• Self-reported complaints of dyspnea or fatigue > 3 months after SARS-CoV-2 infection confirmed with PCR, serology test or COVID-19 Reporting and Data System (CO-RADS) score 4/5.

Exclusion Criteria

• Inability or unwilling to give informed consent.
• History of claustrophobia or feeling of inability to tolerate supine position for the PET/CT scans.
• Individuals who are pregnant or currently breastfeeding are not eligible to participate

Study & Design

• Study Type: OBSERVATIONAL
• Study Design: Not specified

Primary Outcome Measures

Name	Time	Method
Pulmonary FAP expression	Day 1	To compare pulmonary FAP expression between patients with persistent PASC and patients recovered from PASC. Pulmonary FAP expression will be measured via the pulmonary FAPI uptake on the \[68Ga\]FAPI-46 PET/CT scan. Uptake is measured as whole lung SULmean (standardized uptake value corrected for lean body mass) corrected for the background signal (bloodpool). Resulting in the target-to-background ratio (TBR) of the whole lung.

Secondary Outcome Measures

Name	Time	Method
Whole body FAP expression	Day 1	To compare whole body FAPI uptake in patients with persistent PASC vs patients recovered from PASC. Whole body FAPI uptake is measured in the muscle via automated segmentation. Mean muscle uptake values are calculated.
Pulmonary FAP expression vs clinical endpoints	Day 1	To compare pulmonary FAPI uptake (expressed as the mean of the whole lung) to clinical endpoints (e.g. lung function, 6-minute walking test (6-MWT) and self-reported daily impairments assessed by several questionnaires).
Whole body FAP expression vs clinical endpoints	Day 1	To compare whole body FAPI uptake (expressed as the mean of the whole lung) to clinical endpoints (e.g. 6-minute walking test (6-MWT) and self-reported daily impairments assessed by several questionnaires).
Serum biomarkers	Day 1	To explorer serum biomarkers (e.g. soluble FAP and cytokines/growthfactors) and cellular phenotypes of inlammation and remodelling in relation to FAPI uptake (expressed as TBRmean of the whole lung).