Characteristics of mental health implications and plasma metabolomics in patients recently recovered from COVID-19

Abstract

This study aimed to explore the associations between cerebral white matter (WM) alterations, mental health status, and metabolism in recovered COVID-19 patients. We included 28 recovered COVID-19 patients and 27 healthy controls between April 2020 and June 2020. Demographic data, the mental health scores, diffusion-tensor imaging (DTI) data, and plasma metabolomics were collected and compared between the two groups. Tract-based spatial statistics and graph theory approaches were used for DTI data analysis. Untargeted metabolomics analysis of the plasma was performed. Correlation analyses were performed between these characteristics. Recovered COVID-19 patients showed decreased fractional anisotropy, increased mean diffusivity and radial diffusivity values in widespread brain regions, and significantly lower global efficiency, longer shortest path length, and less nodal local efficiency in superior occipital gyrus (all, P < 0.05, Bonferroni corrected). Our results also demonstrated significantly different plasma metabolic profiling in recovered COVID-19 patients even at 3 months after their hospital discharge, which was mainly related to purine pathways, amino acids, lipids, and amine metabolism. Certain regions with cerebral WM alterations in the recovered patients showed significant correlations with different metabolites and the mental health scores. We observed multiple alterations in both WM integrity and plasma metabolomics that may explain the deteriorated mental health of recovered COVID-19 patients. These findings may provide potential biomarkers for the mental health evaluation for the recovered COVID-19 patients and potential targets for novel therapeutics.

Fig. 1. Differences in the white matter microstructures between recovered COVID-19 patients and healthy controls (HC).

Compared with HC, recovered COVID-19 patients showed significantly decreased fractional anisotropy (FA) (A), increased radial diffusivity (RD) (B), and increased mean diffusivity (MD) (C) in multiple brain regions (P < 0.05, TFCE corrected), whereas no difference in axial diffusivity (AD) was observed.

Fig. 2. Correlations between DTI network metrics, the various DTI-derived indices, and the mental health scores.

A Correlations between DTI network metrics, the various DTI-derived indices, and the mental health scores in recovered COVID-19 patients. Each cell contains the correlation coefficient corresponding to the color scale. B Scatter plot of the body of corpus callosum (FA) and PTSD-SS score. C Scatter plot of the body of corpus callosum (MD) and PCL-C score. D Scatter plot of Eglob and PCL-C score. E Scatter plot of left posterior thalamic radiation (RD) and GAD-7 score. Eglob global efficiency, Lp shortest path length, GAD-7 the Generalized Anxiety Disorder Screener GAD-7, PCL-C the PTSD checklist-civilian version, PTSD-SS the Posttraumatic Stress Disorder Self-Rating Scale, Rs Spearman’s correlation coefficient. *P < 0.05; **P < 0.01.

Fig. 3. Differential plasma metabolites revealed in recovered COVID-19 patients when compared with healthy controls.

Heat map of 52 differential metabolites from 12 major classes in recovered COVID-19 patients, metabolites levels were displayed by the shades of the color (red and blue present lower level, and higher level, respectively).

Fig. 4. Main disordered pathways of differential metabolites in recovered COVID-19 patients when compared to healthy controls 3 months after discharge.

The color of red and blue for metabolites illustrated that the metabolite was increased or decreased in recovered COVID-19 patients when compared with healthy controls, respectively.

Fig. 5. Correlations between DTI network metrics, the various DTI-derived indices, and the metabonomics characteristics.

A Summary of the correlations between DTI network metrics, the various DTI-derived indices, and the metabonomics characteristics. The color indicates the value of the correlation coefficient of the corresponding correlation (blue, and red are negative and positive correlations, respectively). Correlation with a two-sided α of <0.05 was considered statistically significant and marked with an asterisk. B Scatter plot of xanthosine and body of corpus callosum (FA). C Scatter plot of taurine and right anterior corona radiate (RD). D Scatter plot of arachidonic acid and left cingulum (RD). E Scatter plot of serotonin and left anterior corona radiate (FA). AMP adenosine 5’-monophosphate, ADP adenosine diphosphate, LTD4 leukotriene D4, 12, 13-EODE 12, 13-epoxyoctadec-97-enoic acid, R Pearson’s correlation coefficient.