Metabolic changes assessed by 1H MR spectroscopy in the corpus callosum of post-COVID patients

Abstract

Objective: Many patients with long COVID experience neurological and psychological symptoms. Signal abnormalities on MR images in the corpus callosum have been reported. Knowledge about the metabolic profile in the splenium of the corpus callosum (CCS) may contribute to a better understanding of the pathophysiology of long COVID.

Materials and methods: Eighty-one subjects underwent proton MR spectroscopy examination. The metabolic concentrations of total N-acetylaspartate (NAA), choline-containing compounds (Cho), total creatine (Cr), myo-inositol (mI), and NAA/Cho in the CCS were statistically compared in the group of patients containing 58 subjects with positive IgG COVID-19 antibodies or positive SARS-CoV-2 qPCR test at least two months before the MR and the group of healthy controls containing 23 subjects with negative IgG antibodies.

Results: An age-dependent effect of SARS-CoV-2 on Cho concentrations in the CCS has been observed. Considering the subjective threshold of age = 40 years, older patients showed significantly increased Cho concentrations in the CCS than older healthy controls (p = 0.02). NAA, Cr, and mI were unchanged. All metabolite concentrations in the CCS of younger post-COVID-19 patients remained unaffected by SARS-CoV-2. Cho did not show any difference between symptomatic and asymptomatic patients (p = 0.91).

Discussion: Our results suggest that SARS-CoV-2 disproportionately increases Cho concentration in the CCS among older post-COVID-19 patients compared to younger ones. The observed changes in Cho may be related to the microstructural reorganization in the CCS also reported in diffusion measurements rather than increased membrane turnover. These changes do not seem to be related to neuropsychological problems of the post-COVID-19 patients. Further metabolic studies are recommended to confirm these observations.

Keywords: COVID-19; Metabolism; Proton MR spectroscopy; The splenium of the corpus callosum.

Fig. 1

An example of the spectroscopic voxel position in the splenium of the corpus callosum on a sagittal T1-weighted image and on coronal and transversal T2-weighted MR images. The figure was created in Corel Graphics Suite

Fig. 2

Inclusion graph. MRS: magnetic resonance spectroscopy; PAT: subjects with positive SARS-CoV-2 qPCR test at least two months before the MR examination or positive COVID-19 IgG antibodies (> 22 kU/l); HC: subjects with COVID-19 IgG < 22 kU/l; symptPAT: patients with neuropsychological symptoms; asymptPAT: asymptomatic patients. The figure was created in Corel Graphics Suite

Fig. 3

An example of 1H MR spectrum measured using the PRESS sequence with short echo time from the splenium of the corpus callosum in a symptomatic post-COVID-19 patient and a healthy control. The figure was created in Corel Graphics Suite. a.u.: arbitrary unit; ppm: parts per million; PAT: subjects with COVID-19 IgG antibodies > 22 kU/l or with positive SARS-CoV-2 PCR test at least two months before the MR examination; HC: subjects with COVID-19 IgG < 22 kU/l; Cr: total creatine; mI: myo-inositol; Cho: choline-containing compounds; Glx: glutamine + glutamate; NAA: total N-acetylaspartate

Fig. 4

The linear regression plots of age and the individual metabolic concentrations for the PAT and HC groups. PAT: subjects with COVID-19 IgG antibodies > 22 kU/l or with positive SARS-CoV-2 qPCR test at least two months before the MR examination; symptPAT: patients with neuropsychological symptoms; asymptPAT: asymptomatic patients; HC: subjects with COVID-19 IgG < 22 kU/l; NAA: total N-acetylaspartate; Cho: choline-containing compounds

Fig. 5

Slopes of the linear regression fit of metabolic concentrations – age dependence with their 95% confidence intervals for the symptPAT, asymptPAT, and HC groups. PAT: subjects with COVID-19 IgG antibodies > 22 kU/l or with positive SARS-CoV-2 qPCR test at least 2 months before MR examination; symptPAT: patients with neuropsychological symptoms; asymptPAT: asymptomatic patients; HC: subjects with COVID-19 IgG < 22 kU/l; mI: myo-inositol; Cho: choline-containing compounds; NAA: total N-acetylaspartate; Cr: total creatine; NAA/Cho: NAA/Cho ratio