Poster preview
ePoster
CENTRAL REDOX DYSREGULATION AND MITOCHONDRIAL STRESS IN FATAL COVID-19 SEPSIS: A POSTMORTEM CSF STUDY
Guolu Tangand 6 co-authors
University Medical Center Groningen (UMCG), University of Groningen
FENS Forum 2026 (2026)
Barcelona, Spain
Board PS02-07PM-410
Presentation
Date TBA
Board: PS02-07PM-410
Event Information
Poster Board
PS02-07PM-410
Poster
View posterAbstract
Neurological injury in severe COVID-19 may involve central oxidative stress, yet direct molecular evidence from the central nervous system (CNS) remains limited. Here, we integrated unbiased global cerebrospinal fluid (CSF) proteomics with targeted biochemical redox profiling in a postmortem case control study. CSF was collected from ICU decedents with fatal COVID-19 sepsis (n=7) and age-matched non-COVID ICU controls (n=5), and analysed by data-independent acquisition LC–MS/MS and a reactive species interactome panel.
Proteomics revealed 2,405 CSF proteins across all samples, demonstrating distinct segregation between COVID-19 and controls. To improve robustness in this cohort, a leave-one-out jackknife procedure identified 124 reproducible differentially abundant proteins. This signature highlighted chromatin and nucleosome remodelling, a mitochondrial oxidative stress protein cluster enriched for SOD2, VDAC1, PRDX6, and TST, and a glial and myelin-associated protein cluster.
In parallel, targeted biochemical assays in the same CSF cohort corroborated a marked CNS redox imbalance. Antioxidant defences were affected (all expressed in arbitrary units), with profoundly reduced glutathione (median 7.75 vs 279.25 in controls; ~36-fold lower; p<0.01), and reduced H2S (p<0.01). This occurred alongside increased reactive species, including superoxide (+16%; p<0.01) and peroxynitrite (+9%; p<0.01). Catalase and MPO activities were higher (p<0.01), whereas total SOD activity was lower (p<0.01). Additionally, metal homeostasis was altered, with increased Fe2+ and decreased Cu2+ (p<0.01).
Together, these data indicate that fatal COVID-19 is associated with coordinated CSF signatures of mitochondrial stress and a marked redox imbalance, suggesting that CNS redox dysregulation may contribute to the discrete neuropathological changes observed in these patients.
Proteomics revealed 2,405 CSF proteins across all samples, demonstrating distinct segregation between COVID-19 and controls. To improve robustness in this cohort, a leave-one-out jackknife procedure identified 124 reproducible differentially abundant proteins. This signature highlighted chromatin and nucleosome remodelling, a mitochondrial oxidative stress protein cluster enriched for SOD2, VDAC1, PRDX6, and TST, and a glial and myelin-associated protein cluster.
In parallel, targeted biochemical assays in the same CSF cohort corroborated a marked CNS redox imbalance. Antioxidant defences were affected (all expressed in arbitrary units), with profoundly reduced glutathione (median 7.75 vs 279.25 in controls; ~36-fold lower; p<0.01), and reduced H2S (p<0.01). This occurred alongside increased reactive species, including superoxide (+16%; p<0.01) and peroxynitrite (+9%; p<0.01). Catalase and MPO activities were higher (p<0.01), whereas total SOD activity was lower (p<0.01). Additionally, metal homeostasis was altered, with increased Fe2+ and decreased Cu2+ (p<0.01).
Together, these data indicate that fatal COVID-19 is associated with coordinated CSF signatures of mitochondrial stress and a marked redox imbalance, suggesting that CNS redox dysregulation may contribute to the discrete neuropathological changes observed in these patients.
Recommended posters
INVESTIGATING THE PERIPHERAL IMMUNE LANDSCAPE OF NEUROCOVID: A SINGLE-CELL TRANSCRIPTOMICS AND PLASMA PROTEOMICS APPROACH TOWARD CLINICAL STRATIFICATION
Bidour Hussein, Celia L. Hartmann, Jessica V. Montgomery, Francesca Calcaterra, Susan Seibert, Federico Masserini, Omid Shirvani, Aleksej Frolov, NeuroCOV Consortium, Christiana Franke, Agostino Riva, Harald Prüß, Gabor Petzold, Domenico Mavilio, Elena De Domenico, Joachim L. Schultze, Marc D. Beyer, Caterina Carraro, Anna C. Aschenbrenner
SPIKE PROTEIN DRIVES SYNAPTIC DEFICITS AND INFLAMMATORY MICROGLIA THROUGH A TLR4-DEPENDENT MECHANISM IN HIPPOCAMPAL SLICES
Dalila Mango, Nunzia Maisto, Asia d'Ettorre, Sepideh Dashtiani, Viviana Triaca
COGNITIVE IMPAIRMENT IN LONG COVID: NEUROBIOLOGICAL INSIGHTS FROM RESTING-STATE FMRI IN A LARGE-SCALE COHORT
Andrea Perrottelli, Silvana Galderisi, Mario Amore, Stefano Barlati, Gianmarco Cascino, Mario Cirillo, Daniele Corbo, Giorgio Di Lorenzo, Francesco Di Salle, Fabrizio Esposito, Roberto Gasparotti, Luigi Giuliani, Palmiero Monteleone, Gabriele Nibbio, Lorenzo Onorato, Antonio Vita, Mario Maj
MACROPHAGE MIGRATION INHIBITORY FACTOR (MIF) OVEREXPRESSION INDUCED BY SARS-COV-2 INFECTION PROMOTES NEURAL REGENERATION IN HUMAN BRAIN ORGANOIDS
Andrea Martí Sarrias, Maria C. Puertas, Isabel Turpin-Moreno, Lidia Garrido-Sanz, Ángel Bayón-Gil, Patricia Resa-Infante, Jakub Chojnacki, Maria C. Garcia-Guerrero, Víctor Urrea, Ramón Lorenzo-Redondo, Sandra Acosta, Javier Martinez-Picado
CLEARING THE FOG: DEFINING THE MECHANISMS AND PHENOTYPES OF NEUROLOGICAL LONG COVID IN A MOUSE MODEL
Elizabeth Kleeman, Emmet Keough, Stefanie Bader, Marcel Doerflinger, Anthony Hannan
MODERATE VOLUME REDUCTION BUT REDUCED CONNECTIVITY AND ARTERIAL PERFUSION IN THE HIPPOCAMPUS IN LONG COVID
Víctor Manuel Serrano del Pueblo, Serrano-Heras Gemma, Sandra Cebada-Sánchez, Emilio Artacho-Perula, Romero-Sánchez Carlos M, Jose Carlos Delgado-Gonzállez, Vasiliki Argyropoulou, Feria Inma, Rojas Laura, Mansilla Francisco, Paul A Yushkevich, Tomás Segura, Monica Muñoz López