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. 2021 Sep;48(10):3187-3197.
doi: 10.1007/s00259-021-05294-3. Epub 2021 Mar 7.

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

Martina Sollini  1   2 , Silvia Morbelli  3   4 , Michele Ciccarelli  1 , Maurizio Cecconi  1   2 , Alessio Aghemo  1   2 , Paola Morelli  1   2 , Silvia Chiola  1   2 , Fabrizia Gelardi  5   6 , Arturo Chiti  1   2
Affiliations

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

Martina Sollini et al. Eur J Nucl Med Mol Imaging. 2021 Sep.

Abstract

Purpose: The present study hypothesised that whole-body [18F]FDG-PET/CT might provide insight into the pathophysiology of long COVID.

Methods: We prospectively enrolled 13 adult long COVID patients who complained for at least one persistent symptom for >30 days after infection recovery. A group of 26 melanoma patients with negative PET/CT matched for sex/age was used as controls (2:1 control to case ratio). Qualitative and semi-quantitative analysis of whole-body images was performed. Fisher exact and Mann-Whitney tests were applied to test differences between the two groups. Voxel-based analysis was performed to compare brain metabolism in cases and controls. Cases were further grouped according to prevalent symptoms and analysed accordingly.

Results: In 4/13 long COVID patients, CT images showed lung abnormalities presenting mild [18F]FDG uptake. Many healthy organs/parenchyma SUVs and SUV ratios significantly differed between the two groups (p ≤ 0.05). Long COVID patients exhibited brain hypometabolism in the right parahippocampal gyrus and thalamus (uncorrected p < 0.001 at voxel level). Specific area(s) of hypometabolism characterised patients with persistent anosmia/ageusia, fatigue, and vascular uptake (uncorrected p < 0.005 at voxel level).

Conclusion: [18F]FDG PET/CT acknowledged the multi-organ nature of long COVID, supporting the hypothesis of underlying systemic inflammation. Whole-body images showed increased [18F]FDG uptake in several "target" and "non-target" tissues. We found a typical pattern of brain hypometabolism associated with persistent complaints at the PET time, suggesting a different temporal sequence for brain and whole-body inflammatory changes. This evidence underlined the potential value of whole-body [18F]FDG PET in disclosing the pathophysiology of long COVID.

Keywords: Brain hypometabolism; Chronic COVID syndrome; Infection; Inflammation; Long COVID; SARS-CoV-2; [18F]FDG PET/CT.

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Conflict of interest statement

Dr. Sollini, Morbelli, Ciccarelli, Morelli, Aghemo and Gelardi have nothing to disclose; Dr. Cecconi reports personal fees from Edwards Lifesciences, personal fees from Directed Systems, and personal fees from Cheetah Medical, outside the submitted work; Dr. Chiti reports other from Sanofi, personal fees from AAA, personal fees from Blue Earth Diagnostics, and personal fees from General Electric Healthcare, outside the submitted work.

Figures

Fig. 1
Fig. 1
[18F]FDG-PET/CT images in two long COVID patients with persistent fatigue. MIP image (a) of patient 6 shows moderate [18F]FDG uptake in joints and vessels as confirmed by coronal PET view (red arrows in b. Axial PET (c) and fused PET/CT (d) images show lung abnormalities characterised by mild [18F]FDG uptake (red arrow). MIP image (e) of patient 7 shows high to moderate [18F]FDG uptake in joints, bone marrow, and salivary glands.
Fig. 2
Fig. 2
[18F]FDG-PET/CT images in a female melanoma patient (control group). MIP image (a) shows mild to moderate [18F]FDG uptake in joints, vessels, and bone marrow as confirmed by coronal PET view (red arrows in b).
Fig. 3
Fig. 3
Box-and-whisker plot of the right and left lung semi-quantitative parameters expressed as absolute SUVmax parameter (a), lung SUVmax/liver SUVmax (b), and lung SUVmax/caval vein SUVmean (c) ratios in the group of long COVID
Fig. 4
Fig. 4
Brain [18F]FDG PET analysis. Regions of hypometabolism compared to controls in the 13 long COVID patients (a) and subgroups of patients showing persistence of anosmia (b), fatigue (c), or mild-to-moderate vessel [18F]FDG uptake (d). Regions of significant difference are colour-graded in terms of Z values. Talairach coordinates and further details are available in Table 3 of the supplementary materials
See this image and copyright information in PMC

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