Journal Article

DZNE-2024-01416

http://join2-wiki.gsi.de/foswiki/pub/Main/Artwork/join2_logo100x88.png Persistence of spike protein at the skull-meninges-brain axis may contribute to the neurological sequelae of COVID-19.

Rong, Z. ; Mai, H. ; Ebert, G. ; Kapoor, S. ; Puelles, V. G. ; Czogalla, J. ; Hu, S. ; Su, J. ; Prtvar, D.DZNE* ; 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.Extern* ; Hopfner, F.Extern* ; Ulukaya, S. ; Jeridi, D. ; Mistretta, D. ; Caliskan, Ö. S. ; Wettengel, J. M. ; Cherif, F.DZNE* ; Kolabas, Z. I. ; Molbay, M. ; Horvath, I. ; Zhao, S. ; Krahmer, N. ; Yildirim, A. Ö. ; Ussar, S. ; Herms, J.Extern* ; Huber, T. B. ; Tahirovic, S.DZNE* ; Schwarzmaier, S. M. ; Plesnila, N. ; Höglinger, G.DZNE* ; Ondruschka, B. ; Bechmann, I. ; Protzer, U. ; Elsner, M. ; Bhatia, H. S. ; Hellal, F. ; Ertürk, A.

2024
Elsevier Amsterdam [u.a.]

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Please use a persistent id in citations: doi:10.1016/j.chom.2024.11.007

Abstract: 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.

Keyword(s): COVID-19: metabolism (MeSH) ; COVID-19: virology (MeSH) ; Animals (MeSH) ; Spike Glycoprotein, Coronavirus: metabolism (MeSH) ; Humans (MeSH) ; Mice (MeSH) ; SARS-CoV-2 (MeSH) ; Brain: virology (MeSH) ; Brain: metabolism (MeSH) ; Disease Models, Animal (MeSH) ; Meninges: virology (MeSH) ; Meninges: metabolism (MeSH) ; Skull: virology (MeSH) ; Male (MeSH) ; Female (MeSH) ; Proteomics (MeSH) ; Stroke: metabolism (MeSH) ; Stroke: virology (MeSH) ; Neuroinflammatory Diseases: metabolism (MeSH) ; Neuroinflammatory Diseases: virology (MeSH) ; Mice, Inbred C57BL (MeSH) ; Brain Injuries, Traumatic: metabolism (MeSH) ; Brain Injuries, Traumatic: virology (MeSH) ; SARS-CoV-2 ; brain ; long COVID ; mRNA vaccine ; meninges ; neurodegeneration ; neuroinflammation ; skull ; spike protein ; tissue clearing ; Spike Glycoprotein, Coronavirus ; spike protein, SARS-CoV-2

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Contributing Institute(s):

1. Juvenile Neurodegeneration (AG Tahirovic)
2. Clinical Research (Munich) (Clinical Research (Munich))

Research Program(s):

1. 352 - Disease Mechanisms (POF4-352) (POF4-352)
2. 353 - Clinical and Health Care Research (POF4-353) (POF4-353)

Appears in the scientific report 2024

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Database coverage:
; ; ; BIOSIS Previews ; Biological Abstracts ; Clarivate Analytics Master Journal List ; Current Contents - Life Sciences ; Essential Science Indicators ; IF >= 30 ; JCR ; SCOPUS ; Science Citation Index Expanded ; Web of Science Core Collection

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