TY  - JOUR
AU  - Rong, Zhouyi
AU  - Mai, Hongcheng
AU  - Ebert, Gregor
AU  - Kapoor, Saketh
AU  - Puelles, Victor G
AU  - Czogalla, Jan
AU  - Hu, Senbin
AU  - Su, Jinpeng
AU  - Prtvar, Danilo
AU  - Singh, Inderjeet
AU  - Schädler, Julia
AU  - Delbridge, Claire
AU  - Steinke, Hanno
AU  - Frenzel, Hannah
AU  - Schmidt, Katja
AU  - Braun, Christian
AU  - Bruch, Gina
AU  - Ruf, Viktoria
AU  - Ali, Mayar
AU  - Sühs, Kurt-Wolfram
AU  - Nemati, Mojtaba
AU  - Hopfner, Franziska
AU  - Ulukaya, Selin
AU  - Jeridi, Denise
AU  - Mistretta, Daniele
AU  - Caliskan, Özüm Sehnaz
AU  - Wettengel, Jochen Martin
AU  - Cherif, Fatma
AU  - Kolabas, Zeynep Ilgin
AU  - Molbay, Müge
AU  - Horvath, Izabela
AU  - Zhao, Shan
AU  - Krahmer, Natalie
AU  - Yildirim, Ali Önder
AU  - Ussar, Siegfried
AU  - Herms, Jochen
AU  - Huber, Tobias B
AU  - Tahirovic, Sabina
AU  - Schwarzmaier, Susanne M
AU  - Plesnila, Nikolaus
AU  - Höglinger, Günter
AU  - Ondruschka, Benjamin
AU  - Bechmann, Ingo
AU  - Protzer, Ulrike
AU  - Elsner, Markus
AU  - Bhatia, Harsharan Singh
AU  - Hellal, Farida
AU  - Ertürk, Ali
TI  - Persistence of spike protein at the skull-meninges-brain axis may contribute to the neurological sequelae of COVID-19.
JO  - Cell host and microbe
VL  - 32
IS  - 12
SN  - 1931-3128
CY  - Amsterdam [u.a.]
PB  - Elsevier
M1  - DZNE-2024-01416
SP  - 2112 - 2130.e10
PY  - 2024
AB  - 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.
KW  - COVID-19: metabolism
KW  - COVID-19: virology
KW  - Animals
KW  - Spike Glycoprotein, Coronavirus: metabolism
KW  - Humans
KW  - Mice
KW  - SARS-CoV-2
KW  - Brain: virology
KW  - Brain: metabolism
KW  - Disease Models, Animal
KW  - Meninges: virology
KW  - Meninges: metabolism
KW  - Skull: virology
KW  - Male
KW  - Female
KW  - Proteomics
KW  - Stroke: metabolism
KW  - Stroke: virology
KW  - Neuroinflammatory Diseases: metabolism
KW  - Neuroinflammatory Diseases: virology
KW  - Mice, Inbred C57BL
KW  - Brain Injuries, Traumatic: metabolism
KW  - Brain Injuries, Traumatic: virology
KW  - SARS-CoV-2 (Other)
KW  - brain (Other)
KW  - long COVID (Other)
KW  - mRNA vaccine (Other)
KW  - meninges (Other)
KW  - neurodegeneration (Other)
KW  - neuroinflammation (Other)
KW  - skull (Other)
KW  - spike protein (Other)
KW  - tissue clearing (Other)
KW  - Spike Glycoprotein, Coronavirus (NLM Chemicals)
KW  - spike protein, SARS-CoV-2 (NLM Chemicals)
LB  - PUB:(DE-HGF)16
C6  - pmid:39615487
DO  - DOI:10.1016/j.chom.2024.11.007
UR  - https://pub.dzne.de/record/273942
ER  -