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Next-Generation Sequencing and Proteomics of Cerebrospinal Fluid From COVID-19 Patients With Neurological Manifestations

Authors :
Haijun Wang
Zili Zhang
Junfen Zhou
Shuqing Han
Zhenyu Kang
Haoyu Chuang
Heng Fan
Hongyang Zhao
Lin Wang
Yunjia Ning
Alexey Sarapultsev
Willis X. Li
Jinghong Li
Zhicheng Lin
Shanshan Luo
Nian Xiong
Desheng Hu
Source :
Frontiers in Immunology, Vol 12 (2021)
Publication Year :
2021
Publisher :
Frontiers Media S.A., 2021.

Abstract

The SARS-CoV-2 and its variants are still hitting the world. Ever since the outbreak, neurological involvements as headache, ageusia, and anosmia in COVID-19 patients have been emphasized and reported. But the pathogenesis of these new-onset neurological manifestations in COVID-19 patients is still obscure and controversial. As difficulty always lay in the diagnosis of neurological infection, current reports to validate the presence of SARS-CoV-2 in cerebrospinal fluid (CSF) almost relied on the basic methods and warranted improvement. Here we reported a case series of 8 patients with prominent new-onset neurological manifestations, who were screened out from a patch of 304 COVID-19 confirmed patients. Next-generation sequencing (NGS) and proteomics were conducted in the simultaneously obtained CSF and serum samples of the selected patients, with three non-COVID-19 patients with matched demographic features used as the controls for proteomic analysis. SARS-CoV-2 RNA was detected in the CSF of four COVID-19 patients and was suspicious in the rest four remaining patients by NGS, but was negative in all serum samples. Proteomic analysis revealed that 185 and 59 proteins were differentially expressed in CSF and serum samples, respectively, and that only 20 proteins were shared, indicating that the proteomic changes in CSF were highly specific. Further proteomic annotation highlighted the involvement of complement system, PI3K-Akt signaling pathway, enhanced cellular interaction, and macrophages in the CSF proteomic alterations. This study, equipped with NGS and proteomics, reported a high detection rate of SARS-CoV-2 in the CSF of COVID-19 patients and the proteomic alteration of CSF, which would provide insights into understanding the pathological mechanism of SARS-CoV-2 CNS infection.

Details

Language :
English
ISSN :
16643224 and 95127909
Volume :
12
Database :
Directory of Open Access Journals
Journal :
Frontiers in Immunology
Publication Type :
Academic Journal
Accession number :
edsdoj.9512790975374229b387101c9b81db2f
Document Type :
article
Full Text :
https://doi.org/10.3389/fimmu.2021.782731