IMPACT OF COVID-19 INFECTION ON WHITE MATTER MICROSTRUCTURAL ALTERATIONS IN HEALTHY POPULATION AND MAJOR DEPRESSIVE DISORDER: A MULTIMODAL MRI STUDY
Authors: Sun *Taipeng , Jiang Chenguang , Jiang Wenhao , Chen Gang , Xu Wei , You Linlin , Yuan Yonggui 
Published: February 2025

Abstract

Background
Coronavirus disease-2019(COVID-19) infection has been reported to be associated with multiple neuropsychiatric complications including depression, insomnia, cognitive impairment, and anosmia. However, information on brain alterations in individuals affected by COVID-19 is limited. Consistently, Major Depressive Disorder(MDD) patients also have specific structural and functional brain abnormalities.

Aims & Objectives
We aimed to identify the existence of potential brain changes related to COVID-19 in healthy populations and MDD, comparing individuals with COVID-19 and without COVID-19.

Method
We enrolled 2 populations (healthy population and MDD), four cohorts: 57 healthy controls (HC) with COVID-19, 108 age- and gender-matched HC without COVID-19; 79 MDD with COVID-19, 165 MDD without COVID-19. For all subjects, we acquired T1-weighted MRI, fMRI, and diffusion tensor imaging(DTI), calculated regional cortical thickness, surface area, subcortical volume, Amplitude of Low- Frequency Fluctuations(ALFF), regional homogeneity(ReHo), functional connectivity(FC), fractional anisotropy (FA), and mean diffusivity(MD) to quantify Gray and white matter structural and functional abnormalities. Group comparisons were analyzed with ANCOVA, and bonferroni correction was applied for multiple comparisons.

Results
We found widespread decreased FA values(PBonferroni&lt;0.05) in HC with COVID-19 compared to HC without COVID-19 in 20 white matter tracts, ALFF and ReHo values in white matter tracts between HC with and without COVID-19 had no significant differences after Bonferroni correction. In gray matter, there were no significant differences in cortical thickness, surface area, subcortical volume, ALFF, ReHo, and FC between the two groups. Our study also found FA values were decreased in bilateral Superior longitudinal fasciculus, left Anterior thalamic radiation, left Cingulum (cingulate gyrus), and Forceps minor in MDD with COVID-19 compared to MDD without COVID-19(PBonferroni&lt;0.05). Likewise in healthy populations, ALFF and ReHo values in white matter tracts had no significant differences after Bonferroni correction between the two groups in MDD. In gray matter, we found ALFF values were increased in left Amygdala, left Parahippocampal gyrus, and bilateral Supplementary motor area, and decreased in left Angular gyrus in MDD with COVID-19 compared to MDD without COVID-19. Other gray matter indicator (cortical thickness, surface area, subcortical volume, ReHo, FC) had no significant differences among two MDD groups.

Discussion & Conclusion
COVID-19 significantly impairs the microstructure of white matter fibers in healthy individuals, and exacerbated white matter fibers’ microstructural injury of MDD. Of note, the appearance of COVID-19 induced functional impairment precedes structure impairment of grey matter in MDD. Our study results highlighted that the potential influence of COVID-19 in future neuroimaging studies should be fully considered, especially in white matter studies.