Mary Wilson
Well-known member
posted April 5, 2023
doi: https://doi.org/10.1101/2023.04.04.535604
Zhouyi Rong1,2,15†, Hongcheng Mai1,2,15†, Saketh Kapoor1†, Victor G. Puelles3,4,13,14, Jan Czogalla3,4, Julia Schädler5, Jessica Vering5, Claire Delbridge6, Hanno Steinke7, Hannah Frenzel7, Katja Schmidt7, Özüm Sehnaz Caliskan9, Jochen Martin Wettengel10, Fatma Cherif11, Mayar Ali1,16, Zeynep Ilgin Kolabas1,2,16, Selin Ulukaya1, Izabela Horvath1,17, Shan Zhao1, Natalie Krahmer9, Sabina Tahirovic11, Ali Önder Yildirim12,Tobias B. Huber3,4, Benjamin Ondruschka3,5, Ingo Bechmann7, Gregor Ebert8, Ulrike Protzer10, Harsharan Singh Bhatia1,2, Farida Hellal1,2, Ali Ertürk1,2*
ABSTRACT
Coronavirus 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 e ect 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 ndings suggest that SARS-CoV-2 spike protein tra cking from CNS borders into the brain parenchyma and identi ed di erentially regulated pathways maypresent insights into mechanisms underlying immediate and long-term consequences of SARS-CoV-2 and present diagnostic and therapeutic opportunities.
https://www.biorxiv.org/content/10.1...604v1.full.pdf
doi: https://doi.org/10.1101/2023.04.04.535604
Zhouyi Rong1,2,15†, Hongcheng Mai1,2,15†, Saketh Kapoor1†, Victor G. Puelles3,4,13,14, Jan Czogalla3,4, Julia Schädler5, Jessica Vering5, Claire Delbridge6, Hanno Steinke7, Hannah Frenzel7, Katja Schmidt7, Özüm Sehnaz Caliskan9, Jochen Martin Wettengel10, Fatma Cherif11, Mayar Ali1,16, Zeynep Ilgin Kolabas1,2,16, Selin Ulukaya1, Izabela Horvath1,17, Shan Zhao1, Natalie Krahmer9, Sabina Tahirovic11, Ali Önder Yildirim12,Tobias B. Huber3,4, Benjamin Ondruschka3,5, Ingo Bechmann7, Gregor Ebert8, Ulrike Protzer10, Harsharan Singh Bhatia1,2, Farida Hellal1,2, Ali Ertürk1,2*
ABSTRACT
Coronavirus 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 e ect 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 ndings suggest that SARS-CoV-2 spike protein tra cking from CNS borders into the brain parenchyma and identi ed di erentially regulated pathways maypresent insights into mechanisms underlying immediate and long-term consequences of SARS-CoV-2 and present diagnostic and therapeutic opportunities.
https://www.biorxiv.org/content/10.1...604v1.full.pdf