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

基本信息

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
项目类别：
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

项目摘要

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.

概括 2019 年冠状病毒病（COVID19），由严重急性呼吸系统综合症引起冠状病毒 2 (SARS-CoV-2) 已成为全球大流行病，造成了压倒性的影响发病率和死亡率。虽然新冠病毒的主要表现与以下问题有关：呼吸，新兴研究认识到许多神经系统并发症的存在的患者，到目前为止主要与我们小组报告的脑血管疾病有关其他的。需要紧急的高分辨率分子研究来更好地了解 SARS-Cov-2 冠状病毒针对大脑及其是否对脑血管系统产生影响是通过直接感染、继发性全身性凝血病或两者的组合，对弱势个体未来的风险分层和治疗具有具体影响。这个为期一年的补充的目的是紧急阐明细胞类型的特异性趋向性使用互补单克隆抗体检测原发性 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组和组织学分析工具，并进一步阐明病毒感染性、共表达之间的细胞和分子关联 ACE2 和其他假定的病毒受体靶标以及中枢神经系统病理学相关脑血管疾病、新冠病毒的其他病理生理表现以及预现有的合并症。更好地了解大脑中的新冠病毒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针对感染 SARS-Cov-2 且可能易患神经系统疾病的患者的治疗方案并发症。