SARS-CoV-2 Spike Protein Accumulation in the Skull-Meninges-Brain Axis: Potential Implications for Long-Term Neurological Complications in post-COVID-19

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 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.

Source: Zhouyi Rong, Hongcheng Mai, Saketh Kapoor, Victor G. Puelles, Jan Czogalla, Julia Schädler, Jessica Vering, Claire Delbridge, Hanno Steinke, Hannah Frenzel, Katja Schmidt, Özüm Sehnaz Caliskan, Jochen Martin Wettengel, Fatma Cherif, Mayar Ali, Zeynep Ilgin Kolabas, Selin Ulukaya, Izabela Horvath, Shan Zhao, Natalie Krahmer, Sabina Tahirovic, Ali Önder Yildirim, Tobias B. Huber, Benjamin Ondruschka, Ingo Bechmann, Gregor Ebert, Ulrike Protzer, Harsharan Singh Bhatia, Farida Hellal, Ali Ertürk. SARS-CoV-2 Spike Protein Accumulation in the Skull-Meninges-Brain Axis: Potential Implications for Long-Term Neurological Complications in post-COVID-19. bioRxiv 2023.04.04.535604; doi: https://doi.org/10.1101/2023.04.04.535604 https://www.biorxiv.org/content/10.1101/2023.04.04.535604v1.full (Full text)