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

Eur J Nucl Med Mol Imaging. 2021 Sep;48(10):3187-3197. doi: 10.1007/s00259-021-05294-3. Epub 2021 Mar 7.


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.

MeSH terms

  • Adult
  • COVID-19* / complications
  • Case-Control Studies
  • Fluorodeoxyglucose F18*
  • Humans
  • Positron Emission Tomography Computed Tomography
  • Post-Acute COVID-19 Syndrome
  • Radiopharmaceuticals
  • SARS-CoV-2


  • Radiopharmaceuticals
  • Fluorodeoxyglucose F18