ABSTRACT
Neurological symptoms highlight the need to understand pathophysiologic mechanisms.
Subject(s)
COVID-19/complications , Mental Disorders/etiology , Nervous System Diseases/etiology , Autoimmunity , Brain/immunology , Brain/pathology , COVID-19/immunology , COVID-19/physiopathology , COVID-19/virology , Cerebrospinal Fluid/immunology , Cerebrospinal Fluid/virology , Humans , Mental Disorders/immunology , Mental Disorders/physiopathology , Nervous System Diseases/immunology , Nervous System Diseases/physiopathology , Neuroinflammatory Diseases/etiology , Neuroinflammatory Diseases/immunology , Neuroinflammatory Diseases/physiopathology , SARS-CoV-2/isolation & purification , Post-Acute COVID-19 SyndromeABSTRACT
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.
Subject(s)
COVID-19/immunology , Monocytes/immunology , Nervous System Diseases/immunology , T-Lymphocytes/immunology , COVID-19/cerebrospinal fluid , COVID-19/complications , COVID-19/pathology , Cell Differentiation , Cerebrospinal Fluid/immunology , Encephalitis, Viral/cerebrospinal fluid , Encephalitis, Viral/immunology , Gene Expression Profiling , Humans , Interferons/genetics , Interferons/immunology , Leukocytes/immunology , Lymphocyte Activation , Nervous System Diseases/cerebrospinal fluid , Nervous System Diseases/etiology , Nervous System Diseases/pathology , Receptors, Antigen, T-Cell/genetics , Receptors, Antigen, T-Cell/metabolism , SARS-CoV-2/immunology , Single-Cell AnalysisABSTRACT
BACKGROUND AND PURPOSE: Case series indicating cerebrovascular disorders in coronavirus disease 2019 (COVID-19) have been published. Comprehensive workups, including clinical characteristics, laboratory, electroencephalography, neuroimaging, and cerebrospinal fluid findings, are needed to understand the mechanisms. METHODS: We evaluated 32 consecutive critically ill patients with COVID-19 treated at a tertiary care center from March 9 to April 3, 2020, for concomitant severe central nervous system involvement. Patients identified underwent computed tomography, magnetic resonance imaging, electroencephalography, cerebrospinal fluid analysis, and autopsy in case of death. RESULTS: Of 32 critically ill patients with COVID-19, 8 (25%) had severe central nervous system involvement. Two presented with lacunar ischemic stroke in the early phase and 6 with prolonged impaired consciousness after termination of analgosedation. In all but one with delayed wake-up, neuroimaging or autopsy showed multiple cerebral microbleeds, in 3 with additional subarachnoid hemorrhage and in 2 with additional small ischemic lesions. In 3 patients, intracranial vessel wall sequence magnetic resonance imaging was performed for the first time to our knowledge. All showed contrast enhancement of vessel walls in large cerebral arteries, suggesting vascular wall pathologies with an inflammatory component. Reverse transcription-polymerase chain reactions for SARS-CoV-2 in cerebrospinal fluid were all negative. No intrathecal SARS-CoV-2-specific IgG synthesis was detectable. CONCLUSIONS: Different mechanisms of cerebrovascular disorders might be involved in COVID-19. Acute ischemic stroke might occur early. In a later phase, microinfarctions and vessel wall contrast enhancement occur, indicating small and large cerebral vessels involvement. Central nervous system disorders associated with COVID-19 may lead to long-term disabilities. Mechanisms should be urgently investigated to develop neuroprotective strategies.