An observational study in PASC Post Acute Sequelae of COVID 19, Long COVID and Long Covid-19, sponsored by University Medical Center Groningen. Not yet recruiting. Open to participants aged 20 Years and older, including healthy volunteers. Per ClinicalTrials.gov, last updated 2025-04-04.
Sponsored by University Medical Center Groningen · Observational
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.
7,638 studies on the registry are indexed under COVID-19; 488 are open to participants now.
This study's planned enrollment of 60 is below the median of 260 across 3,135 observational studies indexed under COVID-19.
Browse COVID-19 studies →University Medical Center Groningen is the lead sponsor of 609 studies on the registry; 174 are open to participants now.
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Patients will be recruited from the P4O2 COVID-19 cohort (The Netherlands - www.p4o2.org). If too few patients from the P4O2 cohort are willing or eligible to participate in the LIBERATE study, 'healthy' controls from other cohorts may be included as a third control group to meet the required number of participants.
Exclusion Criteria:
Former PASC patients or healthy controls. Fatigue Severity Scale ≥ 4 at time of inclusion
PASC patients with persistent dyspnea and fatigue. Fatigue Severity Scale ≤ 4 at time of \[68Ga\]FAPI PET/CT after having previously recorded score of ≥ 4 or equivalent.
Patients without self-reported complaints and past SARS-CoV-2 infection (which would have resulted in a Fatigue Severity Scale ≤ 4) or without experienced confirmed SARS-CoV-2 infection.
Pulmonary FAP expression
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.
Time frame: Day 1
Whole body FAP expression
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.
Time frame: Day 1
Pulmonary FAP expression vs clinical endpoints
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).
Time frame: Day 1
Whole body FAP expression vs clinical endpoints
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).
Time frame: Day 1
Serum biomarkers
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).
Time frame: Day 1
HRCT vs pulmonary FAP expression
Visual assessment of HRCT abnormalities matching pulmonary FAPI uptake.
Time frame: Day 1
Muscle biopsies
Patients willing to give additional informed consent for a muscle biopsy will be evaluated for increased muscle FAPI uptake (SUVmax of \>4.5). In these patients an ultrasound guided muscle biopsy will be performed of a high uptake area (\>4.5 SUV) and a low uptake area (\<4 SUV). Tissue examination as well as single cell RNA analysis will be performed to explorer the relation between FAP expression and activated remoddeling programs.
Time frame: Day 1
No study locations are listed for this record.
Plan to share: Undecided — Data will be made available upon reasonable request
No publications or documents are linked to this record.
This study is not yet recruiting, as verified in Apr 2025. You cannot join it, but the record below documents what was studied.
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