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

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...

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Autores principales: Wang, Haijun, Zhang, Zili, Zhou, Junfen, Han, Shuqing, Kang, Zhenyu, Chuang, Haoyu, Fan, Heng, Zhao, Hongyang, Wang, Lin, Ning, Yunjia, Sarapultsev, Alexey, Li, Willis X., Li, Jinghong, Lin, Zhicheng, Luo, Shanshan, Xiong, Nian, Hu, Desheng
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Frontiers Media S.A. 2021
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8695435/
https://www.ncbi.nlm.nih.gov/pubmed/34956212
http://dx.doi.org/10.3389/fimmu.2021.782731
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author Wang, Haijun
Zhang, Zili
Zhou, Junfen
Han, Shuqing
Kang, Zhenyu
Chuang, Haoyu
Fan, Heng
Zhao, Hongyang
Wang, Lin
Ning, Yunjia
Sarapultsev, Alexey
Li, Willis X.
Li, Jinghong
Lin, Zhicheng
Luo, Shanshan
Xiong, Nian
Hu, Desheng
author_facet Wang, Haijun
Zhang, Zili
Zhou, Junfen
Han, Shuqing
Kang, Zhenyu
Chuang, Haoyu
Fan, Heng
Zhao, Hongyang
Wang, Lin
Ning, Yunjia
Sarapultsev, Alexey
Li, Willis X.
Li, Jinghong
Lin, Zhicheng
Luo, Shanshan
Xiong, Nian
Hu, Desheng
author_sort Wang, Haijun
collection PubMed
description 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.
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spelling pubmed-86954352021-12-24 Next-Generation Sequencing and Proteomics of Cerebrospinal Fluid From COVID-19 Patients With Neurological Manifestations Wang, Haijun Zhang, Zili Zhou, Junfen Han, Shuqing Kang, Zhenyu Chuang, Haoyu Fan, Heng Zhao, Hongyang Wang, Lin Ning, Yunjia Sarapultsev, Alexey Li, Willis X. Li, Jinghong Lin, Zhicheng Luo, Shanshan Xiong, Nian Hu, Desheng Front Immunol Immunology 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. Frontiers Media S.A. 2021-12-09 /pmc/articles/PMC8695435/ /pubmed/34956212 http://dx.doi.org/10.3389/fimmu.2021.782731 Text en Copyright © 2021 Wang, Zhang, Zhou, Han, Kang, Chuang, Fan, Zhao, Wang, Ning, Sarapultsev, Li, Li, Lin, Luo, Xiong and Hu https://creativecommons.org/licenses/by/4.0/This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) and the copyright owner(s) are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.
spellingShingle Immunology
Wang, Haijun
Zhang, Zili
Zhou, Junfen
Han, Shuqing
Kang, Zhenyu
Chuang, Haoyu
Fan, Heng
Zhao, Hongyang
Wang, Lin
Ning, Yunjia
Sarapultsev, Alexey
Li, Willis X.
Li, Jinghong
Lin, Zhicheng
Luo, Shanshan
Xiong, Nian
Hu, Desheng
Next-Generation Sequencing and Proteomics of Cerebrospinal Fluid From COVID-19 Patients With Neurological Manifestations
title Next-Generation Sequencing and Proteomics of Cerebrospinal Fluid From COVID-19 Patients With Neurological Manifestations
title_full Next-Generation Sequencing and Proteomics of Cerebrospinal Fluid From COVID-19 Patients With Neurological Manifestations
title_fullStr Next-Generation Sequencing and Proteomics of Cerebrospinal Fluid From COVID-19 Patients With Neurological Manifestations
title_full_unstemmed Next-Generation Sequencing and Proteomics of Cerebrospinal Fluid From COVID-19 Patients With Neurological Manifestations
title_short Next-Generation Sequencing and Proteomics of Cerebrospinal Fluid From COVID-19 Patients With Neurological Manifestations
title_sort next-generation sequencing and proteomics of cerebrospinal fluid from covid-19 patients with neurological manifestations
topic Immunology
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8695435/
https://www.ncbi.nlm.nih.gov/pubmed/34956212
http://dx.doi.org/10.3389/fimmu.2021.782731
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