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

NCT06911476 | Not Yet Recruiting

• 3 other identifiers: 19097ZonMW2024-511294-29-00
• Study Type: observational
• Target: 60
• Locations: 0 countries
• Sites: N/A

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.

Conditions

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

Outcome Measures

Primary Outcomes (1)

• 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.

  Day 1

Secondary Outcomes (4)

• Whole body FAP expression

  Day 1

• Pulmonary FAP expression vs clinical endpoints

  Day 1

• Whole body FAP expression vs clinical endpoints

  Day 1

• Serum biomarkers

  Day 1

Other Outcomes (2)

• HRCT vs pulmonary FAP expression

  Day 1

• Muscle biopsies

  Day 1

Study Arms (3)

Former PASC patients

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

PASC patients

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

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.

Eligibility Criteria

• Age: 20 Years+
• Sex: all
• Healthy Volunteers: Yes
• Age Groups: Adult (18-64), Older Adult (65+)
• Sampling Method: Non-Probability Sample

Study Population

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.

You may qualify if:

• \- 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.

You may not qualify if:

• 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

Sponsors & Collaborators

• University Medical Center Groningen: lead
• Academisch Medisch Centrum - Universiteit van Amsterdam (AMC-UvA): collaborator

Biospecimen

Retention: SAMPLES WITH DNA

Blood, nose brushes and muscle biopsies that will be analysed via single cell RNA (scRNA) analysis

MeSH Terms

Conditions

Post-Acute COVID-19 Syndrome

Condition Hierarchy (Ancestors)

COVID-19; Pneumonia, Viral; Pneumonia; Respiratory Tract Infections; Infections; Virus Diseases; Coronavirus Infections; Coronaviridae Infections; Nidovirales Infections; RNA Virus Infections; Lung Diseases; Respiratory Tract Diseases; Post-Infectious Disorders; Chronic Disease; Disease Attributes; Pathologic Processes; Pathological Conditions, Signs and Symptoms

Study Officials

• J Pillay, MD PhD

  Department of Intensive Care, University Medical Center Groningen

  PRINCIPAL INVESTIGATOR

Central Study Contacts

Research Desk UMCG - LIBERATE

CONTACT

+31652724087; LIBERATE@umcg.nl

Study Design

• Study Type: observational
• Observational Model: CASE CONTROL
• Time Perspective: PROSPECTIVE
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: April 1, 2025
• First Posted: April 4, 2025
• Study Start: May 1, 2025
• Primary Completion: December 1, 2025
• Study Completion: December 1, 2025
• Last Updated: April 4, 2025

Record last verified: 2025-04