tetano
Editor, Senior Moderator
Immunity
. 2020 Dec 23;S1074-7613(20)30539-2.
doi: 10.1016/j.immuni.2020.12.011. Online ahead of print.
Neurological Manifestations of COVID-19 Feature T Cell Exhaustion and Dedifferentiated Monocytes in Cerebrospinal Fluid
Michael Heming[SUP] 1 [/SUP], Xiaolin Li[SUP] 1 [/SUP], Saskia R?uber[SUP] 1 [/SUP], Anne K Mausberg[SUP] 2 [/SUP], Anna-Lena B?rsch[SUP] 1 [/SUP], Maike Hartlehnert[SUP] 1 [/SUP], Arpita Singhal[SUP] 3 [/SUP], I-Na Lu[SUP] 1 [/SUP], Michael Fleischer[SUP] 2 [/SUP], Fabian Szepanowski[SUP] 2 [/SUP], Oliver Witzke[SUP] 4 [/SUP], Thorsten Brenner[SUP] 5 [/SUP], Ulf Dittmer[SUP] 6 [/SUP], Nir Yosef[SUP] 7 [/SUP], Christoph Kleinschnitz[SUP] 2 [/SUP], Heinz Wiendl[SUP] 1 [/SUP], Mark Stettner[SUP] 8 [/SUP], Gerd Meyer Zu H?rste[SUP] 9 [/SUP]
Affiliations
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 autoimmune neurological diseases or with viral encephalitis. The CSF of Neuro-COVID patients exhibited an expansion of dedifferentiated monocytes and of exhausted CD4[SUP]+[/SUP] 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.
Keywords: COVID-19; Neuro-COVID; SARS-CoV-2; T cell exhaustion; cerebrospinal fluid; interferon-stimulated genes; neurological manifestation; single-cell RNA sequencing; transcriptomics.
. 2020 Dec 23;S1074-7613(20)30539-2.
doi: 10.1016/j.immuni.2020.12.011. Online ahead of print.
Neurological Manifestations of COVID-19 Feature T Cell Exhaustion and Dedifferentiated Monocytes in Cerebrospinal Fluid
Michael Heming[SUP] 1 [/SUP], Xiaolin Li[SUP] 1 [/SUP], Saskia R?uber[SUP] 1 [/SUP], Anne K Mausberg[SUP] 2 [/SUP], Anna-Lena B?rsch[SUP] 1 [/SUP], Maike Hartlehnert[SUP] 1 [/SUP], Arpita Singhal[SUP] 3 [/SUP], I-Na Lu[SUP] 1 [/SUP], Michael Fleischer[SUP] 2 [/SUP], Fabian Szepanowski[SUP] 2 [/SUP], Oliver Witzke[SUP] 4 [/SUP], Thorsten Brenner[SUP] 5 [/SUP], Ulf Dittmer[SUP] 6 [/SUP], Nir Yosef[SUP] 7 [/SUP], Christoph Kleinschnitz[SUP] 2 [/SUP], Heinz Wiendl[SUP] 1 [/SUP], Mark Stettner[SUP] 8 [/SUP], Gerd Meyer Zu H?rste[SUP] 9 [/SUP]
Affiliations
- PMID: 33382973
- DOI: 10.1016/j.immuni.2020.12.011
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 autoimmune neurological diseases or with viral encephalitis. The CSF of Neuro-COVID patients exhibited an expansion of dedifferentiated monocytes and of exhausted CD4[SUP]+[/SUP] 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.
Keywords: COVID-19; Neuro-COVID; SARS-CoV-2; T cell exhaustion; cerebrospinal fluid; interferon-stimulated genes; neurological manifestation; single-cell RNA sequencing; transcriptomics.