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.

患有冠状病毒疾病2019（COVID-19）的患者可能会出现神经系统后遗症，例如头痛，神经发炎或脑血管疾病。这些情况（这里称为Neuro-COVID）在患有严重COVID-19的患者中更为常见。为了了解这些神经系统后遗症的病因，我们利用单细胞测序并检查了与非炎性和自身免疫性神经系统疾病或病毒性脑炎患者相比，Neuro-COVID患者的脑脊液（CSF）的免疫细胞谱。Neuro-COVID患者的CSF表现为去分化单核细胞扩增和CD4 ⁺耗尽T细胞。Neuro-COVID CSF白细胞具有丰富的干扰素特征。但是，这没有病毒性脑炎那么明显。曲目库分析显示，与轻度Neuro-COVID患者相比，严重者的克隆性T细胞扩增广泛，干扰素反应减弱。总的来说，我们的研究结果记录了Neuro-COVID患者的CSF免疫区室，并表明在这种情况下抗病毒反应受损。