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000273942 037__ $$aDZNE-2024-01416
000273942 041__ $$aEnglish
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000273942 1001_ $$aRong, Zhouyi$$b0
000273942 245__ $$aPersistence of spike protein at the skull-meninges-brain axis may contribute to the neurological sequelae of COVID-19.
000273942 260__ $$aAmsterdam [u.a.]$$bElsevier$$c2024
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000273942 520__ $$aSARS-CoV-2 infection is associated with long-lasting neurological symptoms, although the underlying mechanisms remain unclear. Using optical clearing and imaging, we observed the accumulation of SARS-CoV-2 spike protein in the skull-meninges-brain axis of human COVID-19 patients, persisting long after viral clearance. Further, biomarkers of neurodegeneration were elevated in the cerebrospinal fluid from long COVID patients, and proteomic analysis of human skull, meninges, and brain samples revealed dysregulated inflammatory pathways and neurodegeneration-associated changes. Similar distribution patterns of the spike protein were observed in SARS-CoV-2-infected mice. Injection of spike protein alone was sufficient to induce neuroinflammation, proteome changes in the skull-meninges-brain axis, anxiety-like behavior, and exacerbated outcomes in mouse models of stroke and traumatic brain injury. Vaccination reduced but did not eliminate spike protein accumulation after infection in mice. Our findings suggest persistent spike protein at the brain borders may contribute to lasting neurological sequelae of COVID-19.
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000273942 650_7 $$2Other$$aSARS-CoV-2
000273942 650_7 $$2Other$$abrain
000273942 650_7 $$2Other$$along COVID
000273942 650_7 $$2Other$$amRNA vaccine
000273942 650_7 $$2Other$$ameninges
000273942 650_7 $$2Other$$aneurodegeneration
000273942 650_7 $$2Other$$aneuroinflammation
000273942 650_7 $$2Other$$askull
000273942 650_7 $$2Other$$aspike protein
000273942 650_7 $$2Other$$atissue clearing
000273942 650_7 $$2NLM Chemicals$$aSpike Glycoprotein, Coronavirus
000273942 650_7 $$2NLM Chemicals$$aspike protein, SARS-CoV-2
000273942 650_2 $$2MeSH$$aCOVID-19: metabolism
000273942 650_2 $$2MeSH$$aCOVID-19: virology
000273942 650_2 $$2MeSH$$aAnimals
000273942 650_2 $$2MeSH$$aSpike Glycoprotein, Coronavirus: metabolism
000273942 650_2 $$2MeSH$$aHumans
000273942 650_2 $$2MeSH$$aMice
000273942 650_2 $$2MeSH$$aSARS-CoV-2
000273942 650_2 $$2MeSH$$aBrain: virology
000273942 650_2 $$2MeSH$$aBrain: metabolism
000273942 650_2 $$2MeSH$$aDisease Models, Animal
000273942 650_2 $$2MeSH$$aMeninges: virology
000273942 650_2 $$2MeSH$$aMeninges: metabolism
000273942 650_2 $$2MeSH$$aSkull: virology
000273942 650_2 $$2MeSH$$aMale
000273942 650_2 $$2MeSH$$aFemale
000273942 650_2 $$2MeSH$$aProteomics
000273942 650_2 $$2MeSH$$aStroke: metabolism
000273942 650_2 $$2MeSH$$aStroke: virology
000273942 650_2 $$2MeSH$$aNeuroinflammatory Diseases: metabolism
000273942 650_2 $$2MeSH$$aNeuroinflammatory Diseases: virology
000273942 650_2 $$2MeSH$$aMice, Inbred C57BL
000273942 650_2 $$2MeSH$$aBrain Injuries, Traumatic: metabolism
000273942 650_2 $$2MeSH$$aBrain Injuries, Traumatic: virology
000273942 7001_ $$aMai, Hongcheng$$b1
000273942 7001_ $$aEbert, Gregor$$b2
000273942 7001_ $$aKapoor, Saketh$$b3
000273942 7001_ $$aPuelles, Victor G$$b4
000273942 7001_ $$aCzogalla, Jan$$b5
000273942 7001_ $$aHu, Senbin$$b6
000273942 7001_ $$aSu, Jinpeng$$b7
000273942 7001_ $$0P:(DE-2719)9002550$$aPrtvar, Danilo$$b8$$udzne
000273942 7001_ $$aSingh, Inderjeet$$b9
000273942 7001_ $$aSchädler, Julia$$b10
000273942 7001_ $$aDelbridge, Claire$$b11
000273942 7001_ $$aSteinke, Hanno$$b12
000273942 7001_ $$aFrenzel, Hannah$$b13
000273942 7001_ $$aSchmidt, Katja$$b14
000273942 7001_ $$aBraun, Christian$$b15
000273942 7001_ $$aBruch, Gina$$b16
000273942 7001_ $$aRuf, Viktoria$$b17
000273942 7001_ $$aAli, Mayar$$b18
000273942 7001_ $$aSühs, Kurt-Wolfram$$b19
000273942 7001_ $$0P:(DE-2719)9002938$$aNemati, Mojtaba$$b20$$udzne
000273942 7001_ $$0P:(DE-2719)9003372$$aHopfner, Franziska$$b21$$udzne
000273942 7001_ $$aUlukaya, Selin$$b22
000273942 7001_ $$aJeridi, Denise$$b23
000273942 7001_ $$aMistretta, Daniele$$b24
000273942 7001_ $$aCaliskan, Özüm Sehnaz$$b25
000273942 7001_ $$aWettengel, Jochen Martin$$b26
000273942 7001_ $$0P:(DE-2719)9003325$$aCherif, Fatma$$b27$$udzne
000273942 7001_ $$aKolabas, Zeynep Ilgin$$b28
000273942 7001_ $$aMolbay, Müge$$b29
000273942 7001_ $$aHorvath, Izabela$$b30
000273942 7001_ $$aZhao, Shan$$b31
000273942 7001_ $$aKrahmer, Natalie$$b32
000273942 7001_ $$aYildirim, Ali Önder$$b33
000273942 7001_ $$aUssar, Siegfried$$b34
000273942 7001_ $$0P:(DE-2719)2810441$$aHerms, Jochen$$b35$$udzne
000273942 7001_ $$aHuber, Tobias B$$b36
000273942 7001_ $$0P:(DE-2719)2442036$$aTahirovic, Sabina$$b37$$udzne
000273942 7001_ $$aSchwarzmaier, Susanne M$$b38
000273942 7001_ $$aPlesnila, Nikolaus$$b39
000273942 7001_ $$0P:(DE-2719)2811373$$aHöglinger, Günter$$b40$$udzne
000273942 7001_ $$aOndruschka, Benjamin$$b41
000273942 7001_ $$aBechmann, Ingo$$b42
000273942 7001_ $$aProtzer, Ulrike$$b43
000273942 7001_ $$aElsner, Markus$$b44
000273942 7001_ $$aBhatia, Harsharan Singh$$b45
000273942 7001_ $$aHellal, Farida$$b46
000273942 7001_ $$aErtürk, Ali$$b47
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