Preprint Neuroinflammatory imaging markers in white matter: insights into the cerebral consequences of post-acute sequelae of COVID-19 PASC, 2024, Clouston +

Neuroinflammatory imaging markers in white matter: insights into the cerebral consequences of post-acute sequelae of COVID-19 PASC
Sean Clouston; Chuan Huang; Jia Ying; Zennur Sekendiz; Minos Kritikos; Ashley Fontana; Lev Bangiyev; Benjamin Luft

Symptoms of coronavirus disease 2019 (COVID-19) can persist for months or years after infection, a condition called Post-Acute Sequelae of COVID-19 (PASC).

Whole-brain white matter and cortical gray matter health were assessed using multi-shell diffusion tensor imaging. Correlational tractography was utilized to dissect the nature and extent of white matter changes. In this study of 42 male essential workers, the most common symptoms of Neurological PASC (n = 24) included fatigue (n = 19) and headache (n = 17).

Participants with neurological PASC demonstrated alterations to whole-brain white matter health when compared to controls made up of uninfected, asymptomatic, or mildly infected controls (n = 18). Large differences were evident between PASC and controls in measures of fractional anisotropy (Cohen’s D=-0.54, P = 0.001) and cortical isotropic diffusion (Cohen’s D = 0.50, P = 0.002). Symptoms were associated with white matter fractional anisotropy (fatigue: rho = -0.62, P < 0.001; headache: rho = -0.66, P < 0.001), as well as nine other measures of white and gray matter health. Brain fog was associated with improved cerebral functioning including improved white matter isotropic diffusion and quantitative anisotropy.

This study identified changes across measures of white and gray matter connectivity, neuroinflammation, and cerebral atrophy that were interrelated and associated with differences in symptoms of PASC. These results provide insights into the long-term cerebral implications of COVID-19.

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Figure 2
Correlational tractography comparing participants with post-acute sequelae of coronavirus disease with controls. Tracts are shown when they are statistically significant as defined by having an estimated false ≥ discovery rate < 0.05 (T 1). Blue tracts are shown to indicate the presence of decreases in the outcome of interest, while red shows tracts where the outcome has increased. Each panel shows four different directional views of the brain, and panels differ by neuroimaging outcome: A) Fractional Anisotropy; B) Mean Diffusivity; C) Axial Diffusivity; D) Radial Diffusivity; E) Isotropic Diffusion.



Figure 3
Violin plots showing Core Fractional Anisotropy levels stratified by Acute Coronavirus disease, 2019, and post-acute sequelae of Coronavirus disease, 2019, characteristics. Nominal p-values, derived from multiple t-tests, are reported. Core FA: Core Fractional Anisotropy. Panels showing A) Acute COVID-19 severity, B) Case status (no COVID, acute COVID only, and post-acute sequelae of COVID-19), C) Grouped years since initial infection, D) duration of post-acute sequelae of COVID-19.



Figure 4
Scatter plots and trend lines showing associations between physical and cognitive functioning in participants with post-acute sequelae of Coronavirus disease, 2019.