Abnormal brain diffusivity in participants with persistent neuropsychiatric symptoms after COVID-19

Huajun Liang; Thomas Ernst; Kenichi Oishi; Meghann C Ryan; Edward Herskovits; Eric Cunningham; Eleanor Wilson; Shyamasundaran Kottilil; Linda Chang

doi:10.1515/nipt-2022-0016

Abnormal brain diffusivity in participants with persistent neuropsychiatric symptoms after COVID-19

NeuroImmune Pharm Ther. 2023 Mar 25;2(1):37-48. doi: 10.1515/nipt-2022-0016. Epub 2023 Jan 5.

Authors

Huajun Liang¹, Thomas Ernst^{1

2}, Kenichi Oishi³, Meghann C Ryan^{1

4}, Edward Herskovits¹, Eric Cunningham¹, Eleanor Wilson⁵, Shyamasundaran Kottilil⁵, Linda Chang^{1

2

6}

Affiliations

¹ Diagnostic Radiology and Nuclear Medicine, University of Maryland School of Medicine, Baltimore, MD, USA.
² Department of Neurology, Johns Hopkins University School of Medicine, Baltimore, MD, USA.
³ Department of Radiology, Johns Hopkins University School of Medicine, Baltimore, MD, USA.
⁴ Program in Neuroscience, University of Maryland School of Medicine, Baltimore, MD, USA.
⁵ Department of Medicine, Division of Infectious Disease, Institute of Human Virology, University of Maryland School of Medicine, Baltimore, MD, USA.
⁶ Department of Neurology, University of Maryland School of Medicine, Baltimore, MD, USA.

Abstract

Objectives: We aimed to compare brain white matter integrity in participants with post-COVID-19 conditions (PCC) and healthy controls.

Methods: We compared cognitive performance (NIH Toolbox^®), psychiatric symptoms and diffusion tensor imaging (DTI) metrics between 23 PCC participants and 24 controls. Fractional anisotropy (FA), axial (AD), radial (RD), and mean (MD) diffusivities were measured in 9 white matter tracts and 6 subcortical regions using MRICloud.

Results: Compared to controls, PCC had similar cognitive performance, but greater psychiatric symptoms and perceived stress, as well as higher FA and lower diffusivities in multiple white matter tracts (ANCOVA-p-values≤0.001-0.048). Amongst women, PCC had higher left amygdala-MD than controls (sex-by-PCC p=0.006). Regardless of COVID-19 history, higher sagittal strata-FA predicted greater fatigue (r=0.48-0.52, p<0.001) in all participants, and higher left amygdala-MD predicted greater fatigue (r=0.61, p<0.001) and anxiety (r=0.69, p<0.001) in women, and higher perceived stress (r=0.45, p=0.002) for all participants.

Conclusions: Microstructural abnormalities are evident in PCC participants averaged six months after COVID-19. The restricted diffusivity (with reduced MD) and higher FA suggest enhanced myelination or increased magnetic susceptibility from iron deposition, as seen in stress conditions. The higher amygdala-MD in female PCC suggests persistent neuroinflammation, which might contribute to their fatigue, anxiety, and perceived stress.

Keywords: COVID-19; amygdala; brain; diffusion tensor imaging; post-COVID conditions.