Long COVID hallmarks on [18F]FDG-PET/CT: a case-control study

Area of Science:

• Nuclear Medicine
• Radiology
• Infectious Diseases
• Neurology

Background:

• Long COVID, a condition characterized by persistent symptoms after SARS-CoV-2 infection, presents a complex pathophysiology that remains incompletely understood.
• Existing diagnostic tools have limitations in fully characterizing the multi-organ systemic effects of long COVID.
• Positron Emission Tomography/Computed Tomography (PET/CT) with fluorodeoxyglucose (FDG) is a valuable imaging modality for assessing cellular metabolic activity and inflammation.

Purpose of the Study:

• To investigate the utility of whole-body [18F]FDG-PET/CT in elucidating the pathophysiology of long COVID.
• To identify potential systemic inflammatory markers and organ-specific metabolic alterations in long COVID patients.
• To correlate imaging findings with prevalent long COVID symptoms.

Main Methods:

• Prospective enrollment of 13 adult long COVID patients with persistent symptoms (>30 days post-recovery).
• Comparison with 26 age- and sex-matched melanoma patients with negative PET/CT scans as controls.
• Qualitative and semi-quantitative analysis of whole-body [18F]FDG-PET/CT images, including voxel-based analysis for brain metabolism.
• Statistical comparison using Fisher exact and Mann-Whitney tests.
• Subgroup analysis based on prevalent symptoms.

Main Results:

• Mild [18F]FDG uptake in lung abnormalities was noted in 4/13 long COVID patients.
• Significant differences in Standardized Uptake Values (SUVs) and SUV ratios were observed in multiple organs/parenchyma between long COVID patients and controls (p ≤ 0.05).
• Long COVID patients demonstrated significant brain hypometabolism in the right parahippocampal gyrus and thalamus (uncorrected p < 0.001).
• Specific patterns of hypometabolism correlated with persistent anosmia/ageusia, fatigue, and vascular uptake (uncorrected p < 0.005).

Conclusions:

• Whole-body [18F]FDG-PET/CT imaging supports the multi-organ nature of long COVID and suggests underlying systemic inflammation.
• The observed brain hypometabolism pattern is associated with persistent long COVID symptoms.
• Findings suggest a potential differential temporal evolution of brain and systemic inflammatory changes in long COVID, underscoring the value of whole-body [18F]FDG-PET/CT for pathophysiological insights.