Mechanistic registry to study whether infection with Corona Virus Disease 2019 (COVID-19) alters atherosclerotic plaque progression

项目摘要/摘要 2019年冠状病毒病(新冠肺炎)(COVID-CT)登记的主要目标是确定 感染严重急性呼吸综合征冠状病毒-2(SARS-CoV-2)，引起 新冠肺炎，导致先前定义的冠状动脉粥样硬化斑块显著进展 解剖性冠状动脉疾病(CAD)。新冠肺炎诱导促炎细胞因子释放和促炎因子释放 我们假设的血栓形成过程将加速动脉粥样硬化斑块的进展。冠状动脉 计算机断层血管造影术(CCTA)是一种可靠的非侵入性方法，唯一能够测量 血管造影术狭窄与动脉粥样硬化斑块的量化和特征。我们集团拥有广泛的 使用CCTA识别关键的动脉粥样硬化斑块特征的大型多中心试验和注册的经验 与进度和主要的CAD事件相关。此外，我们还建议使用一种新的冠状动脉CT标记物 动脉炎症-血管周围脂肪衰减指数(FAI)--一个高度预测急性CAD事件的标志物 并评估冠状动脉炎症的一系列变化。 新冠肺炎正迅速成为主要的死亡原因，大量证据表明，先前存在的冠心病 增加患严重疾病的风险和新冠肺炎的死亡率。通过招募高危、动脉粥样硬化患者 斑块，来自COVID-CT登记的发现将告诉我们持续的炎症反应之间的这种联系 新冠肺炎期间以加速动脉粥样硬化斑块进展为主。如果我们的假设得到证实，那么 临床医生和患者将有明确的信息，病毒感染，如SARS-CoV-2，会改变 炎症环境和加速动脉粥样硬化的进展。重要的是，COVID- 19和CAD将广泛影响对约700万感染SARS-CoV患者的预防性风险评估- 2，还有数百万人尚未在美国接受测试。 到目前为止，关于新冠肺炎是否会导致显著的动脉粥样硬化斑块进展缺乏证据。 在不同种族和民族的CCTA定义的CAD患者中，他们居住在一个社会经济- 多样化的城市环境。目前的建议构成了一种全面的方法来评估临床 新冠肺炎后动脉粥样硬化斑块进展的重要性。目前，心外膜的意义 SARS-CoV-2感染后的冠状动脉损伤尚不清楚。然而，动脉粥样硬化的炎症途径 斑块进展得到了很好的研究，因此，我们的假设得到了这个知识库的支持。这个 拟议的新冠肺炎注册将提供对病毒作用的更好的机械性理解 感染对动脉粥样硬化斑块的影响。

Project Summary / Abstract The primary objective of the corona virus disease 2019 (COVID-19) (COVID-CT) registry is to determine if infection with the severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2), the virus which causes COVID-19, results in marked progression of coronary atherosclerotic plaque in patients with previously defined anatomic coronary artery disease (CAD). COVID-19 induces a pro-inflammatory cytokine release and pro- thrombotic processes that we hypothesize will accelerate atherosclerotic plaque progression. Coronary computed tomographic angiography (CCTA) is a robust noninvasive method uniquely capable of measuring angiographic stenosis and quantifying and characterizing atherosclerotic plaque. Our group has extensive experience in large multicenter trials and registries using CCTA to identify key atherosclerotic plaque features associated with progression and major CAD events. Moreover, we propose use of a novel CT marker of coronary artery inflammation - the perivascular fat attenuation index (FAI) – a marker highly predictive of acute CAD events and to assess serial changes in coronary inflammation. COVID-19 is rapidly becoming a leading cause of death with substantial evidence that pre-existing CAD increases risk of serious illness and mortality from COVID-19. By enrolling patients with high risk, atherosclerotic plaque, findings from the COVID-CT registry will inform this link between the inflammatory response sustained during COVID-19 to accelerated atherosclerotic plaque progression. If our hypotheses are confirmed, then clinicians and patients will have clear information that viral infections, such as SARS-CoV-2, alter the inflammatory milieu and accelerate progression of atherosclerosis. Importantly, a connection between COVID- 19 and CAD will broadly impact preventive risk assessment for the ~7 million patients infected with SARS-CoV- 2 and millions more yet to be tested in the United States. To date, evidence is lacking as to whether the COVID-19 results in marked atherosclerotic plaque progression among racially and ethnically diverse patients with CCTA-defined CAD who reside across a socioeconomically- diverse, urban setting. The present proposal constitutes a comprehensive approach assessing the clinical importance of atherosclerotic plaque progression following COVID-19. Currently, the implications of epicardial coronary injury following SARS-CoV-2 infection is unknown. Yet, the inflammatory pathway of atherosclerotic plaque progression is well studied and, as such, our hypotheses are supported by this knowledge base. The proposed COVID-19 registry is poised to provide an improved mechanistic understanding of the role of viral infection on alterations in atherosclerotic plaque.