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Rong, Z. ; Mai, H. ; Ebert, G. ; Kapoor, S. ; Puelles, V.G.* ; Czogalla, J.* ; Hu, S.* ; Su, J. ; Prtvar, D.* ; Singh, I. ; Schädler, J.* ; Delbridge, C.* ; Steinke, H.* ; Frenzel, H.* ; Schmidt, K.* ; Braun, C.* ; Bruch, G.* ; Ruf, V.* ; Ali, M. ; Sühs, K.W.* ; Nemati, M.* ; Hopfner, F.* ; Ulukaya, S. ; Jeridi, D. ; Mistretta, D. ; Caliskan, Ö.S. ; Wettengel, J.M. ; Cherif, F.* ; Kolabas, Z.I. ; Molbay, M. ; Horvath, I. ; Zhao, S. ; Krahmer, N. ; Yildirim, A.Ö. ; Ussar, S. ; Herms, J.* ; Huber, T.B.* ; Tahirovic, S.* ; Schwarzmaier, S.M.* ; Plesnila, N.* ; Höglinger, G.* ; Ondruschka, B.* ; Bechmann, I.* ; Protzer, U. ; Elsner, M. ; Bhatia, H.S. ; Hellal, F. ; Ertürk, A.

Persistence of spike protein at the skull-meninges-brain axis may contribute to the neurological sequelae of COVID-19.

Cell Host Microbe 32, 2112-2130.e10 (2024)
Publ. Version/Full Text DOI PMC
Open Access Hybrid
Creative Commons Lizenzvertrag
SARS-CoV-2 infection is associated with long-lasting neurological symptoms, although the underlying mechanisms remain unclear. Using optical clearing and imaging, we observed the accumulation of SARS-CoV-2 spike protein in the skull-meninges-brain axis of human COVID-19 patients, persisting long after viral clearance. Further, biomarkers of neurodegeneration were elevated in the cerebrospinal fluid from long COVID patients, and proteomic analysis of human skull, meninges, and brain samples revealed dysregulated inflammatory pathways and neurodegeneration-associated changes. Similar distribution patterns of the spike protein were observed in SARS-CoV-2-infected mice. Injection of spike protein alone was sufficient to induce neuroinflammation, proteome changes in the skull-meninges-brain axis, anxiety-like behavior, and exacerbated outcomes in mouse models of stroke and traumatic brain injury. Vaccination reduced but did not eliminate spike protein accumulation after infection in mice. Our findings suggest persistent spike protein at the brain borders may contribute to lasting neurological sequelae of COVID-19.
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Publication type Article: Journal article
Document type Scientific Article
Keywords Sars-cov-2 ; Brain ; Long Covid ; Mrna Vaccine ; Meninges ; Neurodegeneration ; Neuroinflammation ; Skull ; Spike Protein ; Tissue Clearing; Neutrophil Extracellular Traps; Controlled Cortical Impact; Ischemic-stroke; Coronavirus; Craniotomy; Proteomics; Receptor; Injury; Route; Cells
Language english
Publication Year 2024
HGF-reported in Year 2024
ISSN (print) / ISBN 1931-3128
e-ISSN 1934-6069
Journal Cell Host & Microbe
Quellenangaben Volume: 32, Issue: 12, Pages: 2112-2130.e10 Article Number: , Supplement: ,
Publisher Elsevier
Publishing Place 50 Hampshire St, Floor 5, Cambridge, Ma 02139 Usa
Reviewing status Peer reviewed
Institute(s) Institute for Tissue Engineering and Regenerative Medicine (ITERM)
Institute of Virology (VIRO)
Institute of Diabetes and Obesity (IDO)
Institute of Lung Health and Immunity (LHI)
POF-Topic(s) 30205 - Bioengineering and Digital Health
30203 - Molecular Targets and Therapies
30201 - Metabolic Health
90000 - German Center for Diabetes Research
30202 - Environmental Health
Research field(s) Enabling and Novel Technologies
Immune Response and Infection
Helmholtz Diabetes Center
Lung Research
PSP Element(s) G-505800-001
G-502700-010
G-502700-003
G-502296-001
G-501900-221
G-505000-007
G-502799-701
Grants European Research Council Consolidator grant
NOMIS Hu-man Heart Atlas Project grant (Nomis Foundation)
Vascular Dementia Research Foundation
Deutsche Forschungsgemeinschaft (DFG, German Research Foundation) under Germany's Excellence Strategy within the frame-work of the Munich Cluster for Systems Neurology
German Federal Ministry of Education and Research
(BMBF)
DFG
State of Bavaria
European Union
Helmholtz Association's Initiative and Networking Fund
GoBio project

China Scholarship Council (CSC)
DOI 10.1016/j.chom.2024.11.007
WOS ID 001388863700001
Scopus ID 85211122637
PubMed ID 39615487
Erfassungsdatum 2024-12-06
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