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

Multimodal imaging suggests potential immune-vascular contributions to altered regional brain perfusion and oxygen metabolism in Post-COVID-19 Syndrome | bioRxiv Skip to main content Home About Submit ALERTS / RSS Search for this keyword Advanced Search New Results Multimodal imaging suggests potential immune-vascular contributions to altered regional brain perfusion and oxygen metabolism in Post-COVID-19 Syndrome Daniel Martins , Matthew Burrows , Owen O’ Daily , Ziyuan Cai , Nicole Mariani , Alessandra Borsini , Valeria Mondelli , Brandi Eiff , Silvia Rota , Timothy Nicholson , Laila Rida , Adam Hampshire , Federico Turkheimer , Catherine Morgan , David J. Lythgoe , View ORCID Profile Steven C.R. Williams , Fernando Zelaya doi: https://doi.org/10.64898/2026.01.12.699018 Daniel Martins 1 Department of Neuroimaging, Institute of Psychiatry, Psychology and Neuroscience, King’s College London , UK 2 Department of Clinical Neurosciences and Mental Health, Faculty of Medicine, University of Porto , Portugal 3 RISE-Health (Neurosciences thematic line), Faculty of Medicine, University of Porto , Portugal Find this author on Google Scholar Find this author on PubMed Search for this author on this site For correspondence: Daniel.martins{at}kcl.ac.uk Matthew Burrows 1 Department of Neuroimaging, Institute of Psychiatry, Psychology and Neuroscience, King’s College London , UK Find this author on Google Scholar Find this author on PubMed Search for this author on this site Owen O’ Daily 1 Department of Neuroimaging, Institute of Psychiatry, Psychology and Neuroscience, King’s College London , UK Find this author on Google Scholar Find this author on PubMed Search for this author on this site Ziyuan Cai 1 Department of Neuroimaging, Institute of Psychiatry, Psychology and Neuroscience, King’s College London , UK Find this author on Google Scholar Find this author on PubMed Search for this author on this site Nicole Mariani 4 Department of Psychological Medicine, Institute of Psychiatry, Psychology and Neuroscience, King’s College London , London, UK Find this author on Google Scholar Find this author on PubMed Search for this author on this site Alessandra Borsini 4 Department of Psychological Medicine, Institute of Psychiatry, Psychology and Neuroscience, King’s College London , London, UK Find this author on Google Scholar Find this author on PubMed Search for this author on this site Valeria Mondelli 4 Department of Psychological Medicine, Institute of Psychiatry, Psychology and Neuroscience, King’s College London , London, UK Find this author on Google Scholar Find this author on PubMed Search for this author on this site Brandi Eiff 1 Department of Neuroimaging, Institute of Psychiatry, Psychology and Neuroscience, King’s College London , UK Find this author on Google Scholar Find this author on PubMed Search for this author on this site Silvia Rota 1 Department of Neuroimaging, Institute of Psychiatry, Psychology and Neuroscience, King’s College London , UK Find this author on Google Scholar Find this author on PubMed Search for this author on this site Timothy Nicholson 5 Department of Psychosis Studies, Institute of Psychiatry, Psychology and Neuroscience, King’s College London , London, UK Find this author on Google Scholar Find this author on PubMed Search for this author on this site Laila Rida 1 Department of Neuroimaging, Institute of Psychiatry, Psychology and Neuroscience, King’s College London , UK Find this author on Google Scholar Find this author on PubMed Search for this author on this site Adam Hampshire 1 Department of Neuroimaging, Institute of Psychiatry, Psychology and Neuroscience, King’s College London , UK Find this author on Google Scholar Find this author on PubMed Search for this author on this site Federico Turkheimer 1 Department of Neuroimaging, Institute of Psychiatry, Psychology and Neuroscience, King’s College London , UK 6 Institute for Human and Synthetic Minds, King’s College London , UK Find this author on Google Scholar Find this author on PubMed Search for this author on this site Catherine Morgan 7 School of Psychology and Centre for Brain Research, University of Auckland , New Zealand Find this author on Google Scholar Find this author on PubMed Search for this author on this site David J. Lythgoe 1 Department of Neuroimaging, Institute of Psychiatry, Psychology and Neuroscience, King’s College London , UK Find this author on Google Scholar Find this author on PubMed Search for this author on this site Steven C.R. Williams 1 Department of Neuroimaging, Institute of Psychiatry, Psychology and Neuroscience, King’s College London , UK Find this author on Google Scholar Find this author on PubMed Search for this author on this site ORCID record for Steven C.R. Williams Fernando Zelaya 1 Department of Neuroimaging, Institute of Psychiatry, Psychology and Neuroscience, King’s College London , UK Find this author on Google Scholar Find this author on PubMed Search for this author on this site Abstract Full Text Info/History Metrics Supplementary material Preview PDF 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. Funder Information Declared NIHR Maudsley Biomedical Research Centre, https://ror.org/05fd9ct06 Copyright The copyright holder for this preprint is the author/funder, who has granted bioRxiv a license to display the preprint in perpetuity. It is made available under a CC-BY 4.0 International license . Back to top Previous Next Posted January 13, 2026. Download PDF Supplementary Material Email Thank you for your interest in spreading the word about bioRxiv. NOTE: Your email address is requested solely to identify you as the sender of this article. Your Email * Your Name * Send To * Enter multiple addresses on separate lines or separate them with commas. 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Williams , Fernando Zelaya bioRxiv 2026.01.12.699018; doi: https://doi.org/10.64898/2026.01.12.699018 Share This Article: Copy Citation Tools Multimodal imaging suggests potential immune-vascular contributions to altered regional brain perfusion and oxygen metabolism in Post-COVID-19 Syndrome Daniel Martins , Matthew Burrows , Owen O’ Daily , Ziyuan Cai , Nicole Mariani , Alessandra Borsini , Valeria Mondelli , Brandi Eiff , Silvia Rota , Timothy Nicholson , Laila Rida , Adam Hampshire , Federico Turkheimer , Catherine Morgan , David J. Lythgoe , Steven C.R. 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