Neurological Manifestations of COVID-19 Feature T Cell Exhaustion and Dedifferentiated Monocytes in Cerebrospinal Fluid.
Michael Heming, Xiaolin Li, Saskia Räuber, Anne K Mausberg, Anna-Lena Börsch, Maike Hartlehnert, Arpita Singhal, I-Na Lu, Michael Fleischer, Fabian Szepanowski, Oliver Witzke, Thorsten Brenner, Ulf Dittmer, Nir Yosef, Christoph Kleinschnitz, Heinz Wiendl, Mark Stettner, Gerd Meyer Zu Hörste
Author Information
Michael Heming: Department of Neurology with Institute of Translational Neurology, University Hospital Münster, Münster, Germany.
Xiaolin Li: Department of Neurology with Institute of Translational Neurology, University Hospital Münster, Münster, Germany.
Saskia Räuber: Department of Neurology with Institute of Translational Neurology, University Hospital Münster, Münster, Germany.
Anne K Mausberg: Department of Neurology, University Hospital Essen, Essen, Germany.
Anna-Lena Börsch: Department of Neurology with Institute of Translational Neurology, University Hospital Münster, Münster, Germany.
Maike Hartlehnert: Department of Neurology with Institute of Translational Neurology, University Hospital Münster, Münster, Germany.
Arpita Singhal: Department of Electrical Engineering and Computer Science and Center for Computational Biology, University of California Berkeley, Berkeley, CA, USA.
I-Na Lu: Department of Neurology with Institute of Translational Neurology, University Hospital Münster, Münster, Germany.
Michael Fleischer: Department of Neurology, University Hospital Essen, Essen, Germany.
Fabian Szepanowski: Department of Neurology, University Hospital Essen, Essen, Germany.
Oliver Witzke: Department of Infectious Diseases, West German Centre of Infectious Diseases, University Duisburg-Essen, Germany.
Thorsten Brenner: Department of Anesthesiology and Intensive Care Medicine, University Hospital Essen, University Duisburg-Essen, Essen, Germany.
Ulf Dittmer: Institute for Virology, University Hospital Essen, Germany.
Nir Yosef: Department of Electrical Engineering and Computer Science and Center for Computational Biology, University of California Berkeley, Berkeley, CA, USA; Ragon Institute of MGH, MIT and Harvard, Cambridge, MA, USA; Chan Zuckerberg Biohub, San Francisco, CA, USA.
Christoph Kleinschnitz: Department of Neurology, University Hospital Essen, Essen, Germany.
Heinz Wiendl: Department of Neurology with Institute of Translational Neurology, University Hospital Münster, Münster, Germany.
Mark Stettner: Department of Neurology, University Hospital Essen, Essen, Germany. Electronic address: mark.stettner@uk-essen.de.
Gerd Meyer Zu Hörste: Department of Neurology with Institute of Translational Neurology, University Hospital Münster, Münster, Germany. Electronic address: gerd.meyerzuhoerste@ukmuenster.de.
Patients suffering from Coronavirus disease 2019 (COVID-19) can develop neurological sequelae, such as headache and neuroinflammatory or cerebrovascular disease. These conditions-termed here as Neuro-COVID-are more frequent in patients with severe COVID-19. To understand the etiology of these neurological sequelae, we utilized single-cell sequencing and examined the immune cell profiles from the cerebrospinal fluid (CSF) of Neuro-COVID patients compared with patients with non-inflammatory and autoimmune neurological diseases or with viral encephalitis. The CSF of Neuro-COVID patients exhibited an expansion of dedifferentiated monocytes and of exhausted CD4 T cells. Neuro-COVID CSF leukocytes featured an enriched interferon signature; however, this was less pronounced than in viral encephalitis. Repertoire analysis revealed broad clonal T cell expansion and curtailed interferon response in severe compared with mild Neuro-COVID patients. Collectively, our findings document the CSF immune compartment in Neuro-COVID patients and suggest compromised antiviral responses in this setting.
