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.
Study Type
OBSERVATIONAL
Enrollment
60
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
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