4.7 Article

Cerebrospinal fluid findings in neurological diseases associated with COVID-19 and insights into mechanisms of disease development

Journal

INTERNATIONAL JOURNAL OF INFECTIOUS DISEASES
Volume 102, Issue -, Pages 155-162

Publisher

ELSEVIER SCI LTD
DOI: 10.1016/j.ijid.2020.10.044

Keywords

COVID-19; SARS-CoV-2; Cerebrospinal fluid; Neurofilament light protein; Total Tau protein; Oligoclonal bands

Funding

  1. Fundacao Oswaldo Cruz (FIOCRUZ)

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This study aimed to analyze the cerebrospinal fluid of patients with SARS-CoV-2 infection and neurological manifestations. The findings showed that patients with inflammatory neurological diseases presented with pleocytosis and elevated protein and NfL levels in their CSF, while patients with encephalopathy were mostly older men with evidence of cerebrovascular disease.
Objectives: To analyze the cerebrospinal fluid (CSF) of patients with SARS-CoV-2 infection and neurological manifestations to provide evidence for the understanding of mechanisms associated with central nervous system (CNS) involvement in COVID-19. Methods: Patients (n = 58) were grouped according to their main neurological presentation: headache (n = 14); encephalopathy (n = 24); inflammatory neurological diseases, including meningoencephalitis (n = 4), acute myelitis (n = 3), meningitis (n = 2), acute disseminated encephalomyelitis (ADEM) (n = 2), encephalitis (n = 2), and neuromyelitis optica (n = 1); and Guillain-Barre syndrome (n = 6). Data regarding age, sex, cerebrovascular disease, and intracranial pressure were evaluated in combination with CSF profiles defined by cell counts, total protein and glucose levels, concentration of total Tau and neurofilament light chain (NfL) proteins, oligoclonal band patterns, and detection of SARS-CoV-2 RNA. Results: CSF of patients with inflammatory neurological diseases was characterized by pleocytosis and elevated total protein and NfL levels. Patients with encephalopathy were mostly older men (mean age of 61.0 17.6 years) with evidence of cerebrovascular disease. SARS-CoV-2 RNA in CSF was detected in 2 of 58 cases: a patient with refractory headache, and another patient who developed ADEM four days after onset of COVID-19 symptoms. Three patients presented intrathecal IgG synthesis, and four had identical oligoclonal bands in CSF and serum, indicating systemic inflammation. Conclusion: Patients with neurological manifestations associated with COVID-19 had diverse CSF profiles, even within the same clinical condition. Our findings indicate a possible contribution of viral replication on triggering CNS infiltration by immune cells and the subsequent inflammation promoting neuronal injury. (C) 2020 The Author(s). Published by Elsevier Ltd on behalf of International Society for Infectious Diseases.

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