Brain fog in long COVID: A glutamatergic hypothesis with astrocyte dysfunction accounting for brain PET glucose hypometabolism

Tatiana Horowitz (1) , Luc Pellerin (2) , Eduardo Zimmer (3, 4, 5) , Eric Guedj (6)

1 CERIMED - Centre Européen de Recherche en Imagerie médicale
2 IRMETIST [Poitiers] - Ischémie reperfusion, métabolisme et inflammation stérile en transplantation [U 1313]
3 UFRGS - Universidade Federal do Rio Grande do Sul [Porto Alegre]
4 McGill University = Université McGill [Montréal, Canada]
5 PUC-RS - Pontifícia Universidade Católica do Rio Grande do Sul [Brasil] = Pontifical Catholic University of Rio Grande do Sul [Brazil] = Université catholique pontificale de Rio Grande do Sul [Brésil]
6 IMOTHEP - Imagerie MOléculaire pour applications THéranostiques personnalisées

Brain [18F]FDG-PET scans have revealed a glucose hypometabolic pattern in patients with long COVID. This hypometabolism might reflect primary astrocyte dysfunction. Astrocytes play a key role in regulating energy metabolism to support neuronal and synaptic activity, especially activity involving glutamate as the main neurotransmitter. Neuroinflammation is one of the purported mechanisms to explain brain damage caused by infection with SARS-CoV-2. Microglial activation can trigger reactive astrogliosis, contributing to neuroinflammatory changes. These changes can disturb glutamatergic homeostasis, ultimately leading to cognitive fatigue, which has been described in other clinical situations. We hypothesize that glutamatergic dysregulation related to astrocyte dysfunction could be the substrate of brain PET hypometabolism in long COVID patients with brain fog. Based on these elements, we propose that therapeutics targeting astrocytic glutamate regulation could help mitigate long COVID neurological manifestations.

Keywords: PET; Long COVID; Post-COVID condition; PASC; Glutamate; Metabolism Brain fog; Astrocyte

Domains: Physics [physics]

Tatiana Horowitz, Luc Pellerin, Eduardo Zimmer, Eric Guedj. Brain fog in long COVID: A glutamatergic hypothesis with astrocyte dysfunction accounting for brain PET glucose hypometabolism. Medical Hypotheses, 2023, 180, pp.111186. ⟨10.1016/j.mehy.2023.111186⟩. ⟨hal-04406602⟩