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

University Medical Center Groningen (UMCG)

Status: Not yet enrolling

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

Study type: Observational

Funder types: Other

Identifiers

NCT06911476

19097

2024-511294-29-00 (EU Trial (CTIS) Number)

ZonMW (Other Grant/Funding Number)

Details and patient eligibility

About

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.

Enrollment: 60 estimated patients

Sex: All

Ages: 20+ years old

Volunteers: Accepts Healthy Volunteers

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

Trial design

60 participants in 3 patient groups

Former PASC patients

Description:

Former PASC patients or healthy controls. Fatigue Severity Scale ≥ 4 at time of inclusion

PASC patients

Description:

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.

Back-up cohort - 'healthy' controls

Description:

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.