Author:
Rong Zhouyi,Mai Hongcheng,Kapoor Saketh,Puelles Victor G.,Czogalla Jan,Schädler Julia,Vering Jessica,Delbridge Claire,Steinke Hanno,Frenzel Hannah,Schmidt Katja,Caliskan Özüm Sehnaz,Wettengel Jochen Martin,Cherif Fatma,Ali Mayar,Kolabas Zeynep Ilgin,Ulukaya Selin,Horvath Izabela,Zhao Shan,Krahmer Natalie,Tahirovic Sabina,Yildirim Ali Önder,Huber Tobias B.,Ondruschka Benjamin,Bechmann Ingo,Ebert Gregor,Protzer Ulrike,Bhatia Harsharan Singh,Hellal Farida,Ertürk Ali
Abstract
ABSTRACTCoronavirus disease 2019 (COVID-19), caused by the severe acute respiratory syndrome coronavirus type 2 (SARS-CoV-2), has been associated mainly with a range of neurological symptoms, including brain fog and brain tissue loss, raising concerns about the virus’s acute and potential chronic impact on the central nervous system. In this study, we utilized mouse models and human post-mortem tissues to investigate the presence and distribution of the SARS-CoV-2 spike protein in the skull-meninges-brain axis. Our results revealed the accumulation of the spike protein in the skull marrow, brain meninges, and brain parenchyma. The injection of the spike protein alone caused cell death in the brain, highlighting a direct effect on brain tissue. Furthermore, we observed the presence of spike protein in the skull of deceased long after their COVID-19 infection, suggesting that the spike’s persistence may contribute to long-term neurological symptoms. The spike protein was associated with neutrophil-related pathways and dysregulation of the proteins involved in the PI3K-AKT as well as complement and coagulation pathway. Overall, our findings suggest that SARS-CoV-2 spike protein trafficking from CNS borders into the brain parenchyma and identified differentially regulated pathways may present insights into mechanisms underlying immediate and long-term consequences of SARS-CoV-2 and present diagnostic and therapeutic opportunities.Graphical SummaryShort SummaryThe accumulation of SARS-CoV-2 spike protein in the skull-meninges-brain axis presents potential molecular mechanisms and therapeutic targets for neurological complications in long-COVID-19 patients.
Publisher
Cold Spring Harbor Laboratory
Cited by
6 articles.
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