Assessment of Neuroinflammation in Post‑COVID Syndrome Using Dynamic [18F]FDG PET, MRI, and Immune Biomarkers: A Case‑Control Imaging Study

The primary objective is to evaluate diagnostic differences in post‑COVID syndrome by comparing participants with persistent symptoms to controls without such complaints using quantitative assessment of cerebral cellular metabolism with dynamic [18F]FDG PET, analysis of structural and functional brain parameters with MRI, and measurement of immune‑related blood biomarkers.

The trial enrolled adults aged 30–65 years, inclusive of both female and male participants, who were at least one year post‑diagnosis of mild symptomatic COVID‑19. Candidates were required to have sufficient command of the Dutch language. Participants were divided into two groups: individuals with post‑COVID syndrome exhibiting severe fatigue (≥35 on the CIS‑fatigue scale) and/or concentration difficulties (≥18 on the CIS‑concentration scale), and healthy volunteers without such complaints (fatigue < 35 and concentration < 18). Selection was based on confirmed SARS‑CoV‑2 infection by PCR, serology, antigen test, or typical symptoms with household exposure. General health status was otherwise unrestricted, and no specific dietary or physical‑activity criteria were stipulated. The sponsor did not provide the total number of participants.

The study is a phase‑5, observational imaging trial evaluating neuroinflammation in individuals with post-COVID syndrome compared with asymptomatic controls. Participants are screened for eligibility, undergo a baseline visit that includes intravenous administration of 198 MBq of [18F]FDG, dynamic PET acquisition, structural and functional MRI, and blood sampling for immune‑related parameters. Follow‑up visits at approximately 4 weeks and 12 weeks repeat questionnaire assessments and blood tests, and an end‑of‑study visit at week 16 completes the imaging and final assessments. Participant involvement spans roughly 4 months from screening to study completion. Early termination may occur if a participant withdraws consent, experiences an adverse reaction to the radiotracer, or fails to meet protocol compliance criteria. Primary endpoints are cerebral cellular metabolism measured by dynamic PET, brain MRI parameters, and immune‑related blood markers; secondary endpoints comprise symptom severity scores obtained from validated questionnaires.

The investigational radiopharmaceutical used in the study is Fludeoxyglucose (18F)-Curium, supplied as a solution for injection with a concentration of 185 MBq /ml. Each participant receives a single dose of 198 MBq (megabecquerel) administered by intravenous bolus injection immediately before the PET scan. The product is provided in a sterile vial and is not subject to dose titration; the administered activity is recorded and verified against the prepared dose.

No additional experimental drug or placebo is administered as part of the imaging protocol. Participants may continue any standard‑of‑care therapies for post‑COVID syndrome that are prescribed by their treating physicians, but these treatments are not considered study interventions.

Drug administration is performed by qualified personnel under aseptic conditions. The exact time of injection, injected activity, and any deviations from the planned dose are documented in the study record. Participant compliance with the imaging schedule is monitored through visit logs and electronic case report forms, and any missed or delayed administrations are reported according to protocol specifications.

The efficacy assessment will focus on three primary endpoints: cellular metabolism in the brain as measured with dynamic [18F]FDG PET, structural and functional brain parameters obtained by MRI, and immune‑related blood parameters. A secondary endpoint includes the presence and severity of symptoms evaluated through validated questionnaires. Each endpoint will be quantified using standardized imaging protocols, laboratory analyses, and patient‑reported outcome instruments.

Dynamic PET imaging will be performed after intravenous administration of 198 MBq of [18F]FDG, with kinetic modeling applied to derive metabolic rates. MRI scans will include structural sequences and functional assessments according to established neuroimaging guidelines. Blood samples will be collected for immunological assays, and questionnaire data will be captured using electronic case report forms. Data will be processed with validated software, and statistical comparisons between participants with persistent post‑COVID complaints and control subjects will be conducted to evaluate differences in the defined efficacy parameters.