Imbalanced Brain Neurochemicals in Long COVID and ME/CFS: A Preliminary Study Using MRI

Am J Med. 2025 Mar;138(3):567-574.e1. doi: 10.1016/j.amjmed.2024.04.007. Epub 2024 Apr 6.

Abstract

Purpose: Long COVID and myalgic encephalomyelitis/chronic fatigue syndrome (ME/CFS) patients experience multiple complex symptoms, potentially linked to imbalances in brain neurochemicals. This study aims to measure brain neurochemical levels in long COVID and ME/CFS patients as well as healthy controls to investigate associations with severity measures.

Methods: Magnetic resonance spectroscopy data were acquired with a 3T Prisma magnetic resonance imaging scanner (Siemens Healthcare, Erlangen, Germany). We measured absolute levels of brain neurochemicals in the posterior cingulate cortex in long COVID (n = 17), ME/CFS (n = 17), and healthy controls (n = 10) using Osprey software. The statistical analyses were performed using SPSS version 29 (IBM, Armonk, NY). Age and sex were included as nuisance covariates.

Results: Glutamate levels were significantly higher in patients with long COVID (P = .02) and ME/CFS (P = .017) than in healthy controls. No significant difference was found between the 2 patient cohorts. Additionally, N-acetyl-aspartate levels were significantly higher in long COVID patients (P = .012). Importantly, brain neurochemical levels were associated with self-reported severity measures in long COVID and ME/CFS.

Conclusion: Our study identified significantly elevated glutamate and N-acetyl-aspartate levels in long COVID and ME/CFS patients compared with healthy controls. No significant differences in brain neurochemicals were observed between the 2 patient cohorts, suggesting a potential overlap in their underlying pathology. These findings suggest that imbalanced neurochemicals contribute to the complex symptoms experienced by long COVID and ME/CFS patients.

Keywords: Brain neurochemicals; Glutamate; Long COVID; ME/CFS; MRI; N-acetyl-aspartate (NAA).

MeSH terms

  • Adult
  • Aspartic Acid / analogs & derivatives
  • Aspartic Acid / metabolism
  • Brain* / diagnostic imaging
  • Brain* / metabolism
  • COVID-19* / diagnostic imaging
  • COVID-19* / metabolism
  • Case-Control Studies
  • Fatigue Syndrome, Chronic* / diagnostic imaging
  • Fatigue Syndrome, Chronic* / metabolism
  • Female
  • Glutamic Acid / metabolism
  • Gyrus Cinguli* / diagnostic imaging
  • Gyrus Cinguli* / metabolism
  • Humans
  • Magnetic Resonance Imaging
  • Magnetic Resonance Spectroscopy
  • Male
  • Middle Aged
  • SARS-CoV-2

Substances

  • Glutamic Acid
  • Aspartic Acid
  • N-acetylaspartate