Characteristic functional connectome related to Post-COVID-19 syndrome

Abstract

Post-COVID-19 syndrome is a serious complication following SARS-CoV-2 infection, characterized primarily by fatigue and cognitive complaints. Although first metabolic and structural imaging alterations in Post-COVID-19 syndrome have been identified, their functional consequences remain unknown. Thus, we explored the impact of Post-COVID-19 syndrome on the functional connectome of the brain providing a deeper understanding of pathophysiological mechanisms. In a cross-sectional observational study, resting-state functional magnetic resonance imaging data of 66 patients with Post-COVID-19 syndrome after mild infection (mean age 42.3 years, 57 female) and 57 healthy controls (mean age 42.1 years, 38 female) with a mean time of seven months after acute COVID-19 were analysed using a graph theoretical approach. Network features were quantified using measures including mean distance, nodal degree, betweenness and Katz centrality, and compared between both groups. Graph measures were correlated with clinical measures quantifying fatigue, cognitive function, affective symptoms and sleep disturbances. Alterations were mainly found in the brainstem, olfactory cortex, cingulate cortex, thalamus and cerebellum on average seven months after SARS-CoV-2 infection. Additionally, strong correlations between fatigue severity, cognitive functioning and daytime sleepiness from clinical scales and graph measures were observed. Our study confirms functional relevance of brain imaging changes in Post-COVID-19 syndrome as mediating factors for persistent symptoms and improves our pathophysiological understanding.

Figure 1

Spatial distribution of brain changes. Shown are differences between patients with Post-COVID-19 syndrome and controls (a) as well as Pearson’s correlations between graph measures and FSMC (b). Locations in the sagittal plane are mapped onto a single two-dimensional image. HC Healthy Controls.

Figure 2

Distribution of correlations between selected clinical measures and graph data. Points indicate Pearson’s correlations coefficient between FSMC, PSQI, time since diagnosis and TMT-A and brain regions of respective graph measures including triangle, katz, degree and betweenness.