The goal of this observational study is to investigate the role fibroblasts play in the persistent respiratory complaints after a COVID-19 infection. Fibroblasts are involved in tissue remodeling and repair by creating scar-tissue (fibrosis) after tissue damage has occurred. The hypothesis is that this process of fibrosis is ongoing in patients with persistent complaints. To evaluate the roll of fibroblasts a new type of scan is used that is capable of imaging active fibroblasts, a 68Ga-FAPI PET/CT scan.

Rationale: The pathogenesis of post-acute COVID-19 with respiratory complaints remains unknown. We aim to explore the pulmonary pattern and fibrosis activity in patients with post-acute COVID-19 with respiratory complaints using 68Ga-FAPI Positron Emission Tomography-Computed Tomography (PET/CT) imaging.

Objective: To relate pulmonary fibroblast activity, measured by FAPI-PET/CT at least 3 months after hospital discharge, to interstitial lung abnormalities on high resolution CT (HRCT) at the same time point in post-acute COVID-19 patients with respiratory complaints.

Study design: This is a ZonMw funded single center prospective observational cohort study of post-acute COVID-19 patients with respiratory complaints.

Study population: We will recruit 20 adult patients, all post-ICU or post High-Flow Nasal Oxygen therapy due to there COVID-19 infection, with post-acute COVID-19 and respiratory complaints that will undergo 68Ga-FAPI PET/CT imaging to establish pulmonary fibrosis activity.

Main study parameters/endpoints: To assess the degree of Fibroblast Activation Protein expression on 68Ga-FAPI PET/CT at least 3 months after hospital discharge and to relate this to interstitial lung abnormalities on HRCT at the same time point.

Inclusion Criteria:

• Male patients >18 years and female patients >20 years discharged from hospital after PCR-confirmed COVID-19 infection.
• Previous ICU or ward admission with high flow nasal oxygen (HFNO) or mechanical ventilation.
• Persistent respiratory complaints (shortness of breath) at least 3 months after hospital discharge.

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.
• Severe or significant comorbidity, defined as COPD GOLD stage II or higher and/or known interstitial lung disease.
• Women who are pregnant or breastfeeding.

Adults previously admitted to the ICU or ward requiring mechanical ventilation or high flow nasal oxygen due to their COVID-19 infection with now post-acute COVID-19 and respiratory complaints.

Data underlie the results reported in this article will be shared on reasonably request after deidentification of individual participant data. Only investigators whose proposed use of data is for individual participant data meta-analysis and in line with the signed informed consent are eligible for sharing. Proposals should be directed to r.h.j.a.slart@umcg.nl. To gain access, data requestors will need to sign a data access agreement.

Directly after publication

Only investigators whose proposed use of data is for individual participant data meta-analysis and in line with the signed informed consent are eligible for sharing