Persistence of spike protein at the skull-meninges-brain axis may contribute to the neurological sequelae of COVID-19
Zhouyi Rong, Hongcheng Mai, Gregor Ebert, Saketh Kapoor, Victor G Puelles, Jan Czogalla, Senbin Hu, Jinpeng Su, Danilo Prtvar, Inderjeet Singh, Julia Schädler, Claire Delbridge, Hanno Steinke, Hannah Frenzel, Katja Schmidt, Christian Braun, Gina Bruch, Viktoria Ruf, Mayar Ali, Kurt-Wolfram Sühs, Mojtaba Nemati, Franziska Hopfner, Selin Ulukaya, Denise Jeridi, Daniele Mistretta, Özüm Sehnaz Caliskan, Jochen Martin Wettengel, Fatma Cherif, Zeynep Ilgin Kolabas, Müge Molbay, Izabela Horvath, Shan Zhao, Natalie Krahmer, Ali Önder Yildirim, Siegfried Ussar, Jochen Herms, Tobias B Huber, Sabina Tahirovic, Susanne M Schwarzmaier, Nikolaus Plesnila, Günter Höglinger, Benjamin Ondruschka, Ingo Bechmann, Ulrike Protzer, Markus Elsner, Harsharan Singh Bhatia, Farida Hellal, Ali Ertürk
Cell Host & Microbe, doi:10.1016/j.chom.2024.11.007
Highlights d SARS-CoV-2 spike protein persists in the skull-meningesbrain axis in COVID-19 patients d Spike protein is sufficient to induce brain pathological and behavioral changes in mice d Spike protein enhances brain vulnerability and exacerbates neurological damage in mice d mRNA vaccines reduce, but do not eliminate, the spike burden
AUTHOR CONTRIBUTIONS A.E. conceived and led all aspects of the project. Z.R. and H.M. designed and carried out most of the experiments. G.E. and D.M. performed mouse infection experiments. S.K., M.A., S.U., N.K., O ¨.S.C., and M.M. performed mass spectrometry-based proteomic experiments. Z.R., H.M., G.E., and S.K. performed data analysis and visualization. V.G.P., J. Sch€ adler, T.B.H., and organized human sample collection. J.C. dissected the human skull with the dura mater sample and collected clinical information. S.H. performed TBI experiments and MRI analysis. J. Su and U.P. conducted Comirnaty vaccination. D.P. performed organotypic mouse brain slice culture. I.S. performed western blotting. C.D., H.S., H.F., K.S., C.B., G.B., and I.B. provided human brain and skull samples. V.R. and J.H. provided human brain samples of AD, COVID-19, and control patients from the Neurobiobank Munich. K.-W.S., M.N., and F. Hopfner provided and analyzed CSF samples. D.J. performed MCAo experiments. J.M.W. performed quantitative reverse-transcription PCR (RT-qPCR) analysis. F.C. assisted in sample homogenization. Z.I.K. helped with human skull sample collection. I.H. and S.Z. participated in prototyping experiments. A.E., F. Hellal, and H.S.B. supervised the project. Z.R., H.M., S.K., M.E., and A.E. wrote the manuscript. All authors reviewed and approved the final manuscript.
DECLARATION OF INTERESTS The authors declare no competing interests.
STAR+METHODS Detailed methods are provided..
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