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

Wang, Haijun; Zhang, Zili; Zhou, Jianhua; Han, Shengcheng; Kang, Zhenyu; Chuang, Hao-Yu; Fan, Huiying; Zhao, Hongyang; Wang, Lin; Ning, Yun‐Jia; Sarapultsev, Alexey; Li, Willis X.; Li, Jinghong; Lin, Zhicheng; Luo, Shanshan; Xiong, Nian; Hu, Desheng

doi:10.3389/fimmu.2021.782731

Cited by 16 publications

(12 citation statements)

References 19 publications

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“…RNA sequencing unequivocally confirmed SARS-CoV-2 RNA in half of the (4/8) subjects and indicated "high likelihood" of positivity in the remaining patients. Importantly, RT-PCR and antiviral antibody tests in the CSF samples were negative in all cases [75]. While the strength of a small, single center cohort study is limited, this report provides strong evidence that SARS-CoV-2 invasion of the CSF space likely eludes detection by conventional means and instead requires amplification of the materials for confirmation.…”

Section: Encephalitismentioning

confidence: 75%

Neurological Sequelae of COVID-19

Ahmad¹,

Feigen²,

Vazquez³

et al. 2022

J. Integr. Neurosci.

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Background: Though primarily a pulmonary disease, Coronavirus disease 2019 caused by the SARS-CoV-2 virus can generate devastating disease states that affect multiple organ systems including the central nervous system (CNS). The various neurological disorders associated with COVID-19 range in severity from mild symptoms such as headache, or myalgias to more severe symptoms such as stroke, psychosis, and anosmia. While some of the COVID-19 associated neurological complications are mild and reversible, a significant number of patients suffer from stroke. Studies have shown that COVID-19 infection triggers a wave of inflammatory cytokines that induce endothelial cell dysfunction and generate coagulopathy that increases the risk of stroke or thromboses. Inflammation of the endothelium following infection may also destabilize atherosclerotic plaque and induce thrombotic stroke. Although uncommon, there have also been reports of hemorrhagic stroke associated with COVID-19. The proposed mechanisms include a blood pressure increase caused by infection leading to a reduction in angiotensin converting enzyme-2 (ACE-2) levels that results in an imbalance of the renin-angiotensin system ultimately manifesting inflammation and vasoconstriction. Coagulopathy, as demonstrated by elevated prothrombin time (PT), has also been posited as a factor contributing to hemorrhagics stroke in patients with COVID-19. Other neurological conditions associated with COVID-19 include encephalopathy, anosmia, encephalitis, psychosis, brain fog, headache, depression, and anxiety. Though there are several hypotheses reported in the literature, a unifying pathophysiological mechanism of many of these disorders remains unclear. Pulmonary dysfunction leading to poor oxygenation of the brain may explain encephalopathy and other disorders in COVID-19 patients. Alternatively, a direct invasion of the CNS by the virus or breach of the blood-brain barrier by the systemic cytokines released during infection may be responsible for these conditions. Notwithstanding, the relationship between the inflammatory cytokine levels and conditions such as depression and anxiety is contradictory and perhaps the social isolation during the pandemic may in part be a contributing factor to some of the reported CNS disorders. Objective: In this article, we review the current literature pertaining to some of the most significant and common neurological disorders such as ischemic and hemorrhagic stroke, encephalopathy, encephalitis, brain fog, Long COVID, headache, Guillain-Barre syndrome, depression, anxiety, and sleep disorders in the setting of COVID-19. We summarize some of the most relevant literature to provide a better understanding of the mechanistic details regarding these disorders in order to help physicians monitor and treat patients for significant COVID-19 associated neurologic impairments. Methods: A literature review was carried out by the authors using PubMed with the search terms "COVID-19" and "Neurology", "Neurological Manifestations", "Neuropsychiatric ...

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Section: Encephalitismentioning

confidence: 75%

Neurological Sequelae of COVID-19

Ahmad¹,

Feigen²,

Vazquez³

et al. 2022

J. Integr. Neurosci.

View full text Add to dashboard Cite

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“…While most published studies analyzed in this research area have focused on the following specimen types: blood samples, including serum [11][12][13][14][15][16][17][18][19][20][21] , plasma 12,13,[22][23][24][25][26][27][28][29][30][31][32] , and peripheral blood mononuclear cells (PBMC) 33,34 , there are also studies analyzing FFPE tissue 35,36 , urine [37][38][39][40][41] , fecal 42 , sputum 23 , extracellular vesicle 43,44 , cerebrospinal fluid 21 , semen 45 , colostrum 46 , colostrum 47 and nasopharynx swabs samples 48 . All these studies have provided proteomic snapshots of different aspects of tissues from COVID-19 patients.…”

Section: Introductionmentioning

confidence: 99%

COVIDpro: Database for mining protein dysregulation in patients with COVID-19

Zhang

Luna

Tan

et al. 2022

Preprint

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Background: The ongoing pandemic of the coronavirus disease 2019 (COVID-19) caused by the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) still has limited treatment options partially due to our incomplete understanding of the molecular dysregulations of the COVID-19 patients. We aimed to generate a repository and data analysis tools to examine the modulated proteins underlying COVID-19 patients for the discovery of potential therapeutic targets and diagnostic biomarkers. Methods: We built a web server containing proteomic expression data from COVID-19 patients with a toolset for user-friendly data analysis and visualization. The web resource covers expert-curated proteomic data from COVID-19 patients published before May 2022. The data were collected from ProteomeXchange and from select publications via PubMed searches and aggregated into a comprehensive dataset. Protein expression by disease subgroups across projects was compared by examining differentially expressed proteins. We also visualize differentially expressed pathways and proteins. Moreover, circulating proteins that differentiated severe cases were nominated as predictive biomarkers. Findings: We built and maintain a web server COVIDpro (https://www.guomics.com/covidPro/) containing proteomics data generated by 41 original studies from 32 hospitals worldwide, with data from 3077 patients covering 19 types of clinical specimens, the majority from plasma and sera. 53 protein expression matrices were collected, for a total of 5434 samples and 14,403 unique proteins. Our analyses showed that the lipopolysaccharide-binding protein, as identified in the majority of the studies, was highly expressed in the blood samples of patients with severe disease. A panel of significantly dysregulated proteins was identified to separate patients with severe disease from non-severe disease. Classification of severe disease based on these proteomic signatures on five test sets reached a mean AUC of 0.87 and ACC of 0.80. Interpretation: COVIDpro is an online database with an integrated analysis toolkit. It is a unique and valuable resource for testing hypotheses and identifying proteins or pathways that could be targeted by new treatments of COVID-19 patients.

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“…Given the immunopathogenesis of COVID-19, its role in long-term immunological dysfunction, particularly the autoimmune response, appears to be a distinct possibility. In addition, new evidence suggests that SARS-CoV-2 can infect the central nervous system and the brain cells, particularly microvascular endothelial cells [315,316]. Hypoxia and cytokine storms, when combined with viral invasion, can compromise the blood-brain barrier (BBB) and cause brain tissue damage [306,307].…”

Section: Possible Causes Of the Autoimmune And Anti-inflammatory Proc...mentioning

confidence: 99%

SARS-CoV-2-Specific Immune Response and the Pathogenesis of COVID-19

Gusev

Sarapultsev

Соломатина

et al. 2022

IJMS

Self Cite

181

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The review aims to consolidate research findings on the molecular mechanisms and virulence and pathogenicity characteristics of coronavirus disease (COVID-19) causative agent, severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), and their relevance to four typical stages in the development of acute viral infection. These four stages are invasion; primary blockade of antiviral innate immunity; engagement of the virus’s protection mechanisms against the factors of adaptive immunity; and acute, long-term complications of COVID-19. The invasion stage entails the recognition of the spike protein (S) of SARS-CoV-2 target cell receptors, namely, the main receptor (angiotensin-converting enzyme 2, ACE2), its coreceptors, and potential alternative receptors. The presence of a diverse repertoire of receptors allows SARS-CoV-2 to infect various types of cells, including those not expressing ACE2. During the second stage, the majority of the polyfunctional structural, non-structural, and extra proteins SARS-CoV-2 synthesizes in infected cells are involved in the primary blockage of antiviral innate immunity. A high degree of redundancy and systemic action characterizing these pathogenic factors allows SARS-CoV-2 to overcome antiviral mechanisms at the initial stages of invasion. The third stage includes passive and active protection of the virus from factors of adaptive immunity, overcoming of the barrier function at the focus of inflammation, and generalization of SARS-CoV-2 in the body. The fourth stage is associated with the deployment of variants of acute and long-term complications of COVID-19. SARS-CoV-2’s ability to induce autoimmune and autoinflammatory pathways of tissue invasion and development of both immunosuppressive and hyperergic mechanisms of systemic inflammation is critical at this stage of infection.

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

Cited by 16 publications

References 19 publications

Neurological Sequelae of COVID-19

Neurological Sequelae of COVID-19

COVIDpro: Database for mining protein dysregulation in patients with COVID-19

SARS-CoV-2-Specific Immune Response and the Pathogenesis of COVID-19

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