Immune Cell Interactions in Atherosclerosis

摘要 由SARS-CoV-2(SARS-CoV-2)引起的2019年冠状病毒病(新冠肺炎)大流行， 代表着一场前所未有的世界卫生危机。除了造成肺炎和肺损伤外， 新冠肺炎与心血管事件的风险增加有关，包括血栓形成、肺组织 栓塞症和中风，尤其是危重病人。约10%的重症患者 新冠肺炎发生严重的血栓事件。然而，几乎所有的患者都表现出一些异常。 凝结。因此，SARS-CoV-2感染极大地改变了宿主的凝血级联反应，并在 很多情况下，会导致严重血栓事件的发生。单核细胞是保护我们的白细胞 包括病毒在内的病原体。我们已经报道了单核细胞亚群的巡逻行为， 非经典单核细胞，是维持血管内稳态所必需的。活动或数量的减少 非经典单核细胞导致内皮细胞激活和失调，从而加剧凝血。 事件。我们小组的早期报告显示，新冠肺炎中非经典单核细胞数量减少 患者，这种损失与疾病的严重程度有关。一些单核细胞也可以释放组织 导致凝血的因素。重症冠状病毒感染者单核细胞表达SARS-CoV-2 RNA。这个 表达SARS-CoV-2 RNA的单核细胞亚群尚不清楚，以及这是否源于清除 病毒颗粒或单核细胞直接感染的原因尚不清楚。这种感染如何影响它们释放 组织因子尚不清楚。在目前的研究中，我们将评估从轻度到重度的单核细胞变化。 临床上出现血栓事件和无血栓事件的新冠肺炎患者。我们将对这些进行比较 患者转至健康对照组。我们将检验单核细胞表型和功能是 在新冠肺炎患者中改变推动血液循环中血栓的改变，有助于 血栓事件。我们将通过细胞飞行时间质谱仪和rna-seq技术进行高维分析。 目的：研究轻、重度新冠肺炎患者外周血单核细胞的变化。 临床诊断为血栓事件。每个患者匹配的血浆将进行凝血测试 各种因素。所有单核细胞数据将与临床凝血和免疫细胞数据相关联 有耐心的。了解SARS-CoV-2如何发生血栓形成的机制对于有效 治疗所有新冠肺炎患者，特别是那些有危及生命的血栓事件的患者。

Abstract The coronavirus disease 2019 (COVID-19) pandemic, caused by SARS-Coronavirus-2 (SARS-CoV-2), represents an unprecedented world health crisis. In addition to causing pneumonia and lung injury, COVID-19 is linked to increased risk of cardiovascular events including thrombosis, pulmonary embolism, and stroke, especially in critically-ill patients. Approximately 10% of patients with severe COVID-19 develop a serious thrombotic event. However, almost all patients show some abnormal coagulation. Thus, SARS-CoV-2 infection drastically changes the hosts' coagulation cascade, and in many cases, leads to onset of serious thrombotic events. Monocytes are white blood cells that protect us from pathogens, including viruses. We have reported that the patrolling action of a subset of monocytes, nonclassical monocytes, is required to maintain vascular homeostasis. Reduction in activity or number of nonclassical monocytes causes endothelial activation and dysregulation, thus exacerbating coagulation events. Early reports by our group indicate decreased numbers of nonclassical monocytes in COVID-19 patients, and this loss associates with disease severity. Some monocytes can also release Tissue Factor, which causes clotting. Monocytes from severe COVID patients express SARS-CoV-2 RNA. The monocyte subsets that express SARS-CoV-2 RNA are not known, and whether this is due to scavenging of viral particles or direct infection of monocytes is unclear. How this infection impacts their release of Tissue Factor is not known. In the current study, we will assess monocyte changes in mild to severe COVID-19 patients that clinically present with and without thrombotic events. We will compare these patients to healthy controls. We will test the hypothesis that monocyte phenotype and function is changed in COVID-19 patients to drive thrombotic changes in circulation, contributing to thrombotic events. We will utilize high dimensional profiling via CyTOF mass cytometry and RNA-seq to study monocyte changes in PBMC from mild and severe COVID-19 patients, including those with clinically diagnosed thrombotic events. Matching plasma from each patient will tested for coagulation factors. All monocyte data will be linked with clinical coagulation and immune cell data from each patient. Understanding mechanisms for how thrombosis occurs by SARS-CoV-2 is critical for effective treatment of all COVID-19 patients, especially those with life-threatening thrombotic events.