4.8 Article

Neurological Manifestations of COVID-19 Feature T Cell Exhaustion and Dedifferentiated Monocytes in Cerebrospinal Fluid

Journal

IMMUNITY
Volume 54, Issue 1, Pages 164-+

Publisher

CELL PRESS
DOI: 10.1016/j.immuni.2020.12.011

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Funding

  1. Deutsche Forschungsgemeinschaft (DFG) [ME4050/4-1]
  2. DFG [ME4050/8-1]
  3. Ministerium fur Innovation, Wissenschaft und Forschung (MIWF) des Landes Nordrhein-Westfalen
  4. DFG through Sonderforschungsbereich Collaborative Research Center Transregio (CRC-TR) 128
  5. Foundation University Hospital Essen
  6. Biogen
  7. Rudolf-Ackermann-Stiftung (Stiftung fur Klinische Infektiologie)

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Patients with COVID-19 can develop neurological sequelae referred to as Neuro-COVID, characterized by symptoms like headache and neuroinflammation. Research on the immune cell profiles in the cerebrospinal fluid of Neuro-COVID patients suggests compromised antiviral responses and different immune cell populations in these individuals.
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 auto-immune 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.

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