Neuro-metabolic signature of long COVID

The neuroimaging research conducted by the IMoTheP team on understanding Long COVID has been doubly recognized by AuntMinnie, the leading international media outlet for medical imaging, as among the best scientific articles and images of the year 2024.

Two million people suffer from Long COVID in France. These post-acute sequelae primarily affect young and active individuals, with potential progression to chronic conditions, disability, and stigmatization. The medical and economic impact is estimated at 1% of the global economy.

Molecular neuroimaging research conducted by the IMoTheP team using Positron Emission Tomography (PET) has identified a hypometabolic network linked to olfactory entry pathways. This pattern, observed in both adult and pediatric patients, differs from that of psychiatric disorders or physical deconditioning due to lockdowns. Its severity correlates with the intensity of symptoms, with only partial recovery observed over a 9-month follow-up. This research also highlights a correlation between this late-stage hypometabolism and an initial inflammatory hypermetabolism in the same regions. It could represent an astrocytic signature of glutamatergic dysregulation associated with neuroinflammatory microglial activation.

These studies have significantly contributed to better recognition the cerebral reality of Long COVID (the seminal article has been the most cited in the European Journal of Nuclear Medicine and Molecular Imaging since 2021) and to the development of PET imaging interpretation criteria incorporated into European Nuclear Medicine guidelines.

Figure: Neuro-metabolic signature of COVID long in brain PET with 18F[FDG] (adapted from 10.1007/s00259-021-05215-4 and 10.1007/s00259-021-05215-4)

Images brain pET scan — (A) Brain PET imaging with 18F[FDG] in a healthy subject, showing normal metabolism in axial, sagittal, and coronal slices. (B) Brain PET imaging with 18F[FDG] in a patient with Long COVID, revealing marked hypometabolism, particularly in the brainstem, internal temporal cortex, and cerebellum (indicated by arrows). (C) Diagram illustrating, under physiological conditions, the role of astrocytes in the utilization and recycling of glutamate during glutamatergic neurotransmission. This process ensures optimal use of glucose and lactate by neurons to meet their energy needs. (D) Diagram of suspected dysfunctions in Long COVID: astrocytes may exhibit reduced glutamate uptake and recycling, leading to decreased glucose utilization (observable in 18F[FDG] PET as hypometabolism) and reduced lactate production. These glutamatergic and neurotransmission dysregulations could ultimately damage. (E) 3D visualization of hypometabolic brain abnormalities in patients with Long COVID on 18F[FDG] PET. These abnormalities affect limbic and paralimbic regions connected to olfactory pathways, as well as the brainstem and cerebellum

Partners : Aix-Marseille Université, AP-HM, CNRS, Ecole Centrale Méditerranée, Université de Poitiers, INSERM, Pontifícia Universidade Católica do Rio Grande do Sul (PUCRS), McGill University – Montréal

References :
Horowitz T, Pellerin L, Zimmer ER, Guedj E. Brain fog in long COVID: A glutamatergic hypothesis with astrocyte dysfunction accounting for brain PET glucose hypometabolism. Med Hypotheses. 2023;180:111186. doi:10.1016/j.mehy.2023.111186
Guedj E, Campion JY, Dudouet P, et al. F-FDG brain PET hypometabolism in patients with long COVID. Eur J Nucl Med Mol Imaging. 2021;48(9):2823-2833. doi:10.1007/s00259-021-05215-4

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https://www.auntminnie.com/clinical-news/molecular-imaging/article/15636821/researchers-offer-hypothesis-for-long-covid-brain-fog