Immune Cell Interactions in Atherosclerosis

摘要 2019年冠状病毒病（COVID-19）大流行，由SARS-冠状病毒-2（SARS-CoV-2）引起， 这是一场前所未有的世界卫生危机。除了引起肺炎和肺损伤外， COVID-19与心血管事件的风险增加有关，包括血栓形成、肺动脉高压和肺动脉高压。 栓塞和中风，特别是在危重病人中。大约10%的重度 COVID-19发展为严重血栓形成事件。然而，几乎所有的患者都表现出一些异常， 凝血因此，SARS-CoV-2感染极大地改变了宿主的凝血级联反应， 在许多情况下，导致严重血栓形成事件的发生。单核细胞是保护我们的白色血细胞 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作用， 非经典单核细胞是维持血管稳态所必需的。活动或数量减少 非经典单核细胞引起内皮活化和失调，从而加剧凝血 事件我们小组的早期报告表明COVID-19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 凝血因子，导致凝血。来自严重COVID患者的单核细胞表达SARS-CoV-2 RNA。的 表达SARS-CoV-2 RNA的单核细胞亚群尚不清楚，这是否是由于清除 病毒颗粒或单核细胞的直接感染尚不清楚。这种感染如何影响他们释放的 组织因子未知。在目前的研究中，我们将评估单核细胞的变化，在轻度至重度 COVID-19患者在临床上出现和不出现血栓形成事件。我们将比较这些 患者与健康对照。我们将检验单核细胞的表型和功能是 改变了COVID-19患者的血液循环，导致了血栓性变化， 血栓形成事件。我们将通过CyTOF质谱细胞术和RNA-seq 研究轻度和重度COVID-19患者PBMC中的单核细胞变化，包括那些 临床诊断的血栓形成事件。将对每例患者的匹配血浆进行凝血试验 因素所有单核细胞数据将与来自每个研究的临床凝血和免疫细胞数据相关联。 病人了解SARS-CoV-2如何导致血栓形成的机制对于有效预防和治疗SARS-CoV-2感染至关重要。 治疗所有COVID-19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.