Dados do Trabalho

Título

SERUM LEVELS OF NEUROFILAMENT LIGHT CHAIN, GLIAL FIBRILLARY ACIDIC PROTEIN, UBIQUITIN CARBOXY-TERMINAL HYDROLASE L1 AND TAU PROTEIN IN COVID-19 INFECTED PATIENTS DURING THE PANDEMIC FIRST WAVE: EARLY NERVOUS SYSTEM INVOLVEMENT AND SEVERE OUTCOME

Resumo

SARS-CoV-2 infection can lead to highly heterogeneous clinical outcomes, ranging from no or mild symptoms to severe cases with need for life support in intensive care units (ICU) and death risk. The search for predictors able to forecast disease severity at patient admission to direct clinical choices would be beneficial to set priorities and optimize interventions. Central nervous system biomarkers might reflect early multi-organ involvement of Coronavirus Disease 19 (COVID-19), typical of patients with more severe disease evolution. Neurofilament light chain (NfL) is a protein of central and peripheral neurons validated as a nervous system damage biomarker in a variety of neurological diseases. Glial fibrillary acidic protein (GFAP) is highly expressed in astrocytes and increasingly used as a serum biomarker of astrocytic activation/injury. Ubiquitin carboxy-terminal hydrolase L1 (UCH-L1) is a neuronal specific protein frequently used for indicating brain damage induced by viral infections. Tau protein is mostly expressed by neurons, implicated in the pathogenesis of brain damage, especially in neurodegenerative diseases. This study aims to investigate whether NfL, GFAP, UCH-L1 and Tau protein provide non-redundant prognostic value to COVID-19 severity. So, the objective of this study is to investigate these biomarkers (NfL, GFAP, UCH-L1 and Tau) in the plasma of patients with severe and mild COVID-19.
An observational study with 106 participants, comprising 73 patients with COVID-19 admitted to intensive care unit (ICU), 9 COVID-19 patients with mild symptoms and 24 healthy controls. Blood samples were taken from all participants and Single molecule array (SIMOA) was used to analyze NfL, GFAP, UCH-L1, and total Tau. The ICU participants were collected at the moment of the admission in the ICU and the COVID-19 outpatients at the beginning of symptoms. Graph prism was used to compare results of the ICU group, outpatients and healthy controls, in each protein. In our findings, NfL, GFAP, UCH-L1, and total tau levels were significantly increased in patients with severe or critical COVID-19 compared to outpatients (p<0.0001) and controls (p <0.0001), independently of nervous system involvement. No relevant difference was observed between outpatients and control groups. These results indicate the early involvement of the nervous system measured by serum neurodegeneration biomarkers as an important risk factor in prognosis of COVID-19 outcome.

Palavras Chave

COVID-19, biomarkers, neurodegeneration, SARS-CoV-2, neuroinfection