Cerebrospinal fluid analysis in patients with COVID-19-associated central nervous system manifestations: a systematic review

ABSTRACT

Background: Central nervous system (CNS) symptoms may occur in patients with acute COVID-19. The role of CSF examination in these patients remains to be established. Objective: A systematic review of CSF findings relating to COVID-19 was carried out. Methods: CSF parameters, including cytological and biochemical analyses, SARS-CoV-2 RT-PCR and other CSF markers, were recorded and analyzed among patients with acute COVID-19 and one of the following CNS syndromes: stroke, encephalopathy, encephalitis, inflammatory syndromes, seizure, headache and meningitis. Results: Increased white blood cells and/or increased protein concentration were found in 52.7% of the patients with encephalitis, 29.4% of the patients with encephalopathy and 46.7% of the patients with inflammatory syndromes (P < 0.05). CSF RT-PCR for SARS-CoV-2 was positive in 17.35% of the patients with encephalitis and less than 3.5% of the patients with encephalopathy or inflammatory syndromes (P < 0.05). Intrathecal production of immunoglobulins was found in only 8% of the cases. More than 85% of the patients had increased CSF cytokines and chemokines. Increased CSF neurofilament light chain (NfL) and CSF Tau were found in 71% and 36% of the cases, respectively. Conclusion: Non-specific inflammatory CSF abnormalities were frequently found in patients with COVID-19 CNS syndromes. The increase in neurodegeneration biomarkers suggests that neuronal damage occurs, with long-term consequences that are still unknown.

RESUMO

Antecedentes: O comprometimento do sistema nervoso central (SNC) pode ocorrer em pacientes com COVID-19. O papel do exame do LCR nesses casos ainda não foi precisamente estabelecido. Objetivo: Foi realizada uma revisão sistemática dos achados do LCR em pacientes com COVID-19 e comprometimento do SNC. Métodos: Os parâmetros do LCR, incluindo análises citológicas e bioquímicas, RT-PCR para o SARS-CoV-2, além de outros marcadores liquóricos, foram registrados e analisados em pacientes com as seguintes síndromes: acidente vascular cerebral, encefalopatia, encefalite, síndromes inflamatórias, crises epilépticas, cefaleia e meningite. Resultados: Aumento de leucócitos e/ou aumento da concentração de proteína foram encontradas em 52,7% dos pacientes com encefalite, 29,4% dos pacientes com encefalopatia e 46,7% dos pacientes com outras síndromes inflamatórias (P<0,05). A RT-PCR em LCR para identificação SARS-CoV-2 foi positiva em 17,35% dos pacientes com encefalite e menos de 3,5% dos pacientes com encefalopatia ou síndromes inflamatórias (P<0,05). A produção intratecal de imunoglobulinas foi encontrada em apenas 8% dos casos. Mais de 85% dos pacientes apresentavam aumento de citocinas e quimiocinas no LCR. Foi identificado aumento do neurofilamento de cadeia leve (NfL) em 71% e da proteína Tau em 36% dos casos. Conclusão: Alterações inflamatórias leves e inespecíficas foram frequentes em pacientes com manifestações neurológicas do SNC associadas à COVID-19. O aumento de biomarcadores de neurodegeneração sugere a possibilidade de dano neuronal, com consequências de longo prazo ainda desconhecidas.

Keywords:

COVID-19 - Cerebrospinal Fluid - Encephalitis - Polymerase Chain Reaction - Headache

Palavras-chave:

COVID-19 - Líquido cefalorraquidiano - Encefalite - Reação em Cadeia da Polimerase - Cefaleia

Authors’ contributions:

RBD: conceptualization, data curation, formal analysis, investigation, methodology, writing-original draft, writing-review & editing; FBVML: conceptualization, formal analysis, methodology, validation, visualization; CS: conceptualization, validation, visualization.

Publication History

Received: 29 March 2021

Accepted: 22 June 2021

Article published online:
30 January 2023

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