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

doi:10.1016/j.immuni.2020.12.011

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

Research output: Contribution to journal › Article › peer-review

Abstract

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.

Original language	English
Pages (from-to)	164-175.e6
Number of pages	18
Journal	Immunity
Volume	54
Issue number	1
DOIs	https://doi.org/10.1016/j.immuni.2020.12.011
State	Published - 12 Jan 2021
Externally published	Yes

All Science Journal Classification (ASJC) codes

Immunology and Allergy
Immunology
Infectious Diseases

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10.1016/j.immuni.2020.12.011

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Heming, M., Li, X., Räuber, S., Mausberg, A. K., Börsch, A. L., Hartlehnert, M., Singhal, A., Lu, I. N., Fleischer, M., Szepanowski, F., Witzke, O., Brenner, T., Dittmer, U., Yosef, N., Kleinschnitz, C., Wiendl, H., Stettner, M., & Meyer zu Hörste, G. (2021). Neurological Manifestations of COVID-19 Feature T Cell Exhaustion and Dedifferentiated Monocytes in Cerebrospinal Fluid. Immunity, 54(1), 164-175.e6. https://doi.org/10.1016/j.immuni.2020.12.011

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

abstract = "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.",

author = "Michael Heming and Xiaolin Li and Saskia R{\"a}uber and Mausberg, {Anne K.} and B{\"o}rsch, {Anna Lena} and Maike Hartlehnert and Arpita Singhal and Lu, {I. Na} and Michael Fleischer and Fabian Szepanowski and Oliver Witzke and Thorsten Brenner and Ulf Dittmer and Nir Yosef and Christoph Kleinschnitz and Heinz Wiendl and Mark Stettner and {Meyer zu H{\"o}rste}, Gerd",

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doi = "10.1016/j.immuni.2020.12.011",

language = "الإنجليزيّة",

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Heming, M, Li, X, Räuber, S, Mausberg, AK, Börsch, AL, Hartlehnert, M, Singhal, A, Lu, IN, Fleischer, M, Szepanowski, F, Witzke, O, Brenner, T, Dittmer, U, Yosef, N, Kleinschnitz, C, Wiendl, H, Stettner, M & Meyer zu Hörste, G 2021, 'Neurological Manifestations of COVID-19 Feature T Cell Exhaustion and Dedifferentiated Monocytes in Cerebrospinal Fluid', Immunity, vol. 54, no. 1, pp. 164-175.e6. https://doi.org/10.1016/j.immuni.2020.12.011

TY - JOUR

T1 - Neurological Manifestations of COVID-19 Feature T Cell Exhaustion and Dedifferentiated Monocytes in Cerebrospinal Fluid

AU - Heming, Michael

AU - Li, Xiaolin

AU - Räuber, Saskia

AU - Mausberg, Anne K.

AU - Börsch, Anna Lena

AU - Hartlehnert, Maike

AU - Singhal, Arpita

AU - Lu, I. Na

AU - Fleischer, Michael

AU - Szepanowski, Fabian

AU - Witzke, Oliver

AU - Brenner, Thorsten

AU - Dittmer, Ulf

AU - Yosef, Nir

AU - Kleinschnitz, Christoph

AU - Wiendl, Heinz

AU - Stettner, Mark

AU - Meyer zu Hörste, Gerd

PY - 2021/1/12

Y1 - 2021/1/12

N2 - 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.

AB - 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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DO - 10.1016/j.immuni.2020.12.011

M3 - مقالة

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SN - 1074-7613

VL - 54

SP - 164-175.e6

JO - Immunity

JF - Immunity

IS - 1

ER -

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

Abstract

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