Hippocampal neurometabolic and structural changes from pre-to post-COVID-19: A case-series study

Neurological complications of the COVID-19 infection may be caused in part by local neurochemical and structural abnormalities that could not be detected during routine medical examinations. We examined within subject neurometabolic and structural brain alterations from pre-to post-COVID-19 in the hippocampal region of three elderly individuals (aged 63-68 years) who had a COVID-19 infection with mild symptoms. Patients were participating in an interventional study in which they were closely monitored at the time they were diagnosed with COVID-19. Patients 1 and 2 just completed 18-20 resistance training sessions prior to their diagnosis. Patient 3 was assigned to a non-training condition in the same study.

Whole brain magnetic resonance imaging (MRI) images and proton magnetic resonance spectroscopy (¹H-MRS) of the left hippocampus were collected before and after infection. Structural and spectroscopic imaging measures post-COVID-19 were contrasted to the pre-COVID-19 measures and were compared with values for Minimal Detectable Change at 95% (MDC₉₅) and 90% (MDC₉₀) confidence from a group of six elderly (aged 60-79 years) without COVID-19 that participated in the same study.

After SARS-COV-2 infection, we observed a reduction of glutamate-glutamine (Glx) in Patients 1 and 2 (≥ 42.0%) and elevation of myo-inositol (mIns) and N-acetyl-aspartate (NAA) in Patient 3 (≥ 36.4%); all > MDC₉₀. MRI findings showed increased (Patients 1 and 2) or unchanged (Patient 3) hippocampal volume.

Overall, findings from this exploratory study suggest that mild COVID-19 infection could be associated with development of local neuroinflammation and reduced glutamate levels in the hippocampus. Our ¹H-MRS findings may have clinical value for explaining chronic neurological and psychological complaints in COVID-19 long-haulers.