Evidence of Impaired Neuroimmune System in Post‐COVID Syndrome—A Whole Brain Magnetic Resonance Spectroscopy Study, 2025, Hennemann et al

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Evidence of Impaired Neuroimmune System in Post‐COVID Syndrome—A Whole Brain Magnetic Resonance Spectroscopy Study

Spoiler: Authors

Hennemann, Ann‐Katrin; Mahmoudi, Nima; Döring, Katja; Lanfermann, Heinrich; Weissenborn, Karin; Dirks, Meike; Ding, Xiao‐Qi

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Abstract
Chronic fatigue, mood disturbances, and cognitive deficits characterize the neurological post‐COVID syndrome (PCS). This study aimed to find out if PCS shows a diagnostic brain metabolic pattern that might also support clarification of the PCS pathology.

Whole brain proton magnetic resonance spectroscopy imaging (wbMRSI) was applied to assess brain metabolites in PCS patients. Patients' data were compared to those of matched healthy controls examined before the COVID pandemic. Patients underwent clinical and neuropsychological assessment and filled in self‐report questionnaires related to fatigue, mood, and health‐related quality of life.

Thirty PCS patients were enrolled into the study. WbMRSI showed significantly reduced levels of brain myo‐inositol, which is considered as representative of astrocyte and microglia activity, in the frontal, temporal and parietal lobes, bilaterally, and in the cerebellum of the patients compared to controls.

Patients' creatine was higher in the left frontal lobe and the combined glutamate/glutamine peak was lower in the right parietal lobe. N ‐acetyl‐aspartate, an indicator of neuronal integrity, as well as choline that reflects cell membrane turnover, showed no group differences. The findings suggest an alteration of the neuroimmune system in PCS patients, without indication of disturbed neuronal integrity or alteration of the cerebral energy metabolism.

Web | DOI | Journal of Medical Virology | Open Access

 

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Myo‐inositol (mI)—a sugar alcohol and main player in the inositol family—is found predominantly in astrocytes. It is considered a marker for glial cell activation and neuroinflammation. Myo‐inositol increases have been observed in several neuroinflammatory diseases, but also in neurodegenerative diseases with a chronic pro‐inflammatory state, such as Alzheimer's disease, for example.

Myo‐inositol increases are usually considered to represent both activated astrocytes and microglia. Indeed, neuroinflammation is characterized by a cross‐talk between these two cell types.

the main finding was significantly decreased myoinositol levels bilaterally in the frontal, temporal, and parietal lobes and in the cerebellum of the patients, with an accentuation in the right hemisphere. In addition, decreased Glx in the right parietal lobe and increased tCr in the left frontal lobe as well as a significant increase in linewidth in the frontal, temporal, and parietal lobes were observed in the patients compared to controls.

To conclude, a nearly generalized decrease of brain myoinositol levels is evident in our PCS patients, suggesting a long‐lasting influence of the SARS‐CoV‐2 infection on their brain immunoactivity. A functional downregulation of astrocytes may be a possible explanation.

 

[SNT Gatchaman]

The second finding of our study refers to linewidth. Linewidth is a measure of the homogeneity of the spectra. An increase of linewidth has been observed with age and with increasing BMI […] Moreover, spectral linewidth differs between male and female subjects. Since patients and controls are matched for age, sex, and BMI in this study, the difference in linewidth between patients and controls suggests disease‐related structural alterations of the respective brain regions or alterations of perfusion. […] Another possible cause of the linewidth difference could be a difference in tissue water concentration between the groups.