Multimodal imaging suggests potential immune-vascular contributions to altered regional brain perfusion and oxygen metabolism in Post-COVID-19 Syndrome

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The study used multimodal MRI (structural MRI, arterial spin labeling for regional cerebral blood flow, and asymmetric spin echo imaging for oxygen extraction fraction and cerebral metabolic rate of oxygen consumption) in 40 individuals with prior mild SARS-CoV-2 infection, including 20 with post-COVID-19 syndrome persistent fatigue and 20 recovered matched controls. It found PCS-related increases in CMRO□ in the hippocampus and decreases in CMRO□ in the anterior cingulate cortex, with most hippocampal subregions showing elevated OEF and CMRO□ except the entorhinal cortex, and whole-brain perfusion differences with increased perfusion in salience-related regions but decreased perfusion in posterior cortical and cerebellar areas despite no grey matter volume differences. Higher hippocampal metabolism correlated positively with cognitive performance, while lower ACC CMRO□ associated with depressive symptoms, reduced motivation, and higher serum TNF-α and GFAP, consistent with neurovascular uncoupling possibly involving immune-glial activation. The paper does not discuss endometriosis or adenomyosis; it was included in the corpus via a keyword match in the upstream search index.

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Abstract

Post-COVID-19 Syndrome (PCS) frequently presents with persistent fatigue, cognitive impairment, and emotional symptoms. Although structural brain changes remain subtle, growing evidence implicates functional and metabolic disruptions in ongoing symptomatology. We used multimodal MRI to investigate cerebral perfusion and oxygen metabolism in PCS and examined their associations with cognitive function and peripheral biomarkers. We enrolled 40 individuals with prior mild SARS-CoV-2 infection, including 20 with persistent fatigue and 20 recovered controls matched for age, sex, BMI, and acute COVID-19 severity. Participants underwent structural MRI, arterial spin labelling (ASL) to quantify regional cerebral blood flow (CBF), and asymmetric spin echo imaging to estimate oxygen extraction fraction (OEF) and cerebral metabolic rate of oxygen consumption (CMRO□). We assessed cognition using an online battery and measured serum levels of TNF-α, IL-6, IL-8, IL-13, IFN-γ, GFAP, and S100β, alongside blood routine tests. We performed ANCOVAs on predefined regions of interest (hippocampus, anterior cingulate cortex [ACC], insula, amygdala, striatum), followed by Bayesian inference and exploratory whole-brain analyses. PCS participants showed increased CMRO□ in the hippocampus and decreased CMRO□ in the ACC. Subfield analysis revealed elevated OEF and CMRO□ across most hippocampal regions, excluding the entorhinal cortex. Whole-brain analyses identified increased perfusion in salience-related regions (insula, ACC, thalamus) and decreased perfusion in posterior cortical and cerebellar areas, in the absence of grey matter volume differences. Higher hippocampal metabolism positively correlated with cognitive performance, suggesting compensatory adaptation to sustain function. In contrast, lower ACC CMRO□ correlated with depressive symptoms, reduced motivation, and elevated TNF-α and GFAP, consistent with neurovascular uncoupling possibly driven by immune-glial activation. These findings reveal distinct physiological disruptions in PCS, with potential implications for stratified, metabolism-focused interventions.
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Abstract Post-COVID-19 Syndrome (PCS) frequently presents with persistent fatigue, cognitive impairment, and emotional symptoms. Although structural brain changes remain subtle, growing evidence implicates functional and metabolic disruptions in ongoing symptomatology. We used multimodal MRI to investigate cerebral perfusion and oxygen metabolism in PCS and examined their associations with cognitive function and peripheral biomarkers. We enrolled 40 individuals with prior mild SARS-CoV-2 infection, including 20 with persistent fatigue and 20 recovered controls matched for age, sex, BMI, and acute COVID-19 severity. Participants underwent structural MRI, arterial spin labelling (ASL) to quantify regional cerebral blood flow (CBF), and asymmetric spin echo imaging to estimate oxygen extraction fraction (OEF) and cerebral metabolic rate of oxygen consumption (CMRO□). We assessed cognition using an online battery and measured serum levels of TNF-α, IL-6, IL-8, IL-13, IFN-γ, GFAP, and S100β, alongside blood routine tests. We performed ANCOVAs on predefined regions of interest (hippocampus, anterior cingulate cortex [ACC], insula, amygdala, striatum), followed by Bayesian inference and exploratory whole-brain analyses. PCS participants showed increased CMRO□ in the hippocampus and decreased CMRO□ in the ACC. Subfield analysis revealed elevated OEF and CMRO□ across most hippocampal regions, excluding the entorhinal cortex. Whole-brain analyses identified increased perfusion in salience-related regions (insula, ACC, thalamus) and decreased perfusion in posterior cortical and cerebellar areas, in the absence of grey matter volume differences. Higher hippocampal metabolism positively correlated with cognitive performance, suggesting compensatory adaptation to sustain function. In contrast, lower ACC CMRO□ correlated with depressive symptoms, reduced motivation, and elevated TNF-α and GFAP, consistent with neurovascular uncoupling possibly driven by immune-glial activation. These findings reveal distinct physiological disruptions in PCS, with potential implications for stratified, metabolism-focused interventions. Competing Interest Statement The authors have declared no competing interest.

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