Resolving SARS-Cov-2 tropism and COVID19 pathology in the brain

解决大脑中的 SARS-Cov-2 趋向性和 COVID19 病理学

• 批准号: 10170946
• 负责人: Nadejda Mincheva Tsankova
• 金额: $ 33.9万
• 依托单位: ICAHN SCHOOL OF MEDICINE AT MOUNT SINAI
• 依托单位国家: 美国
• 财政年份: 2020
• 资助国家: 美国
• 起止时间: 2020-01-01 至 2023-12-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/10170946
• 关键词: 2019-nCoV; Affect; Antibodies; Autopsy; Biological; Blood Coagulation Disorders; Blood Vessels; Brain; Brain region; COVID-19; Cell Nucleus; Cells; Cerebrovascular Disorders; Cerebrovascular system; Communities; Coronavirus; Corpus striatum structure; Data; Diabetes Mellitus; Endothelium; Evaluation; Formalin; Freezing; Functional disorder; Future; Histologic; Human; Hypertension; Immunofluorescence Immunologic; Individual; Infarction; Infection; Inflammation; Knowledge; Label; Molecular; Molecular Analysis; Morbidity - disease rate; Neuraxis; Neurologic; Neurons; Pathologic; Pathology; Patients; Pharmaceutical Preparations; Reporting; Resolution; Resources; Respiration; Risk; Risk stratification; Role; Sampling; Smoking; Specimen; Therapeutic; Tissues; Translating; Treatment Protocols; Tropism; Vascular Endothelium; Viral; Viral Load result; Virus; Virus Receptors; base; biobank; brain cell; brain tissue; cell type; cerebrovascular; clinically relevant; comorbidity; coronavirus disease; differential expression; effective therapy; inflammatory marker; mortality; neuropathology; next generation sequencing; novel; pandemic disease; patient stratification; personalized medicine; relating to nervous system; tool; transcriptome sequencing; transcriptomics; viral RNA

SUMMARY Coronavirus disease 2019 (COVID19), caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), has emerged as a global pandemic, causing overwhelming morbidity and mortality. While the main manifestations of COVID19 relate to problems with respiration, emerging studies recognize the presence of neurological complications in a number of patients, so far primarily related to cerebrovascular disease as reported by our group and others. Urgent high-resolution molecular studies are needed to understand better how the SARS-Cov-2 coronavirus targets the brain and whether its effects on the cerebral vasculature are through direct infection, secondary systemic coagulopathy, or a combination of both, which carries specific implications for future risk stratification and treatment in vulnerable individuals. The purpose of this one-year supplement is to urgently elucidate the cell-type specific tropism of the SARS-CoV-2 virus in primary COVID19 autopsy brain tissue using complementary single cell transcriptomic and histological analysis tools already established by our team, and to elucidate further the cellular and molecular associations between viral infectivity, co-expression of ACE2 and other putative viral receptor targets, and central nervous system pathology related to cerebrovascular disease, other pathophysiological manifestations of COVID19, and pre- existent co-morbidities. A better understanding of COVID19 pathophysiology in the brain through this and other studies will inform clinicians of more effective and personalized treatment protocols for patients infected with SARS-Cov-2 who may be predisposed to having neurological complications.

摘要 冠状病毒病2019(COVID19)，由严重急性呼吸综合征引起 冠状病毒2(SARS-CoV-2)已经成为一种全球大流行，造成压倒性的 发病率和死亡率。虽然COVID19的主要表现与以下问题有关 呼吸，新出现的研究承认在许多情况下存在神经并发症 到目前为止，我们小组报告的主要与脑血管疾病有关的患者 其他。迫切需要高分辨率的分子研究，以更好地了解 SARS-CoV-2冠状病毒以脑为靶点及其对脑血管系统的影响 是通过直接感染、继发性全身凝血障碍或两者的组合，即 对脆弱个体未来的风险分层和治疗具有特定的影响。 这本为期一年的补充资料的目的是紧急阐明细胞类型的特异性取向。 应用互补单链抗体检测原代COVID19尸检脑组织中的SARS-CoV-2病毒 我们团队已经建立了细胞转录和组织学分析工具，并 进一步阐明病毒感染性、共表达与细胞和分子之间的联系 ACE2和其他假定的病毒受体靶点，以及与中枢神经系统病理相关的 对脑血管疾病、柯萨奇病毒19的其他病理生理表现，以及前病毒 并存的疾病。更好地了解柯萨奇病毒19在脑内的病理生理学 通过这项研究和其他研究，将为临床医生提供更有效和个性化的治疗方法 针对易患神经系统疾病的SARS-CoV-2感染者的方案 并发症。