Cardiac microstructure and the immune-inflammatory response to SARS-CoV-2

项目总结 在关于与冠状病毒疾病相关的风险和后果的证据迅速增加的情况下 2019年(新冠肺炎)，许多知识鸿沟依然存在。我们和其他人已经报道了某些共病， 包括心血管危险因素在内，使一些人比其他人更容易患上最严重的 新冠肺炎病。新冠肺炎后终末器官后遗症的自然历史、多样性及其决定因素 疾病仍不得而知。除了肺损伤之外，积累的数据不仅强调了短期的 但也可能对心脏产生长期的不良影响。事实上，多份报告显示， 患者心脏结构和功能亚临床和临床异常的发生率 即使是轻微的新冠肺炎病例也在康复中。基于新出现的证据和我们自己的临床 到目前为止的经验，我们假设SARS-CoV-2引发了一种系统性免疫炎症反应， 在很大比例的感染者中导致认识不足的心肌疾病-以一种 随着时间的推移持续存在，并意味着新冠肺炎急性后遗症的长期风险增加。因此，我们 建议扩大新的心脏成像方法的应用范围，以全面表征心脏术后 新冠肺炎的感染性心脏效应。我们的具体目标是：(1)识别和表征纵向 新冠肺炎病急性期后心脏疾病的发展轨迹及相关结果； 以及，(2)描述新冠肺炎疾病免疫-炎症反应的纵向轨迹，以及 它们与感染后心脏病及相关结局的关系。从我们不断增长的来源样本 自2020年3月8日以来住院治疗的12,500名患者中，有12,500人因RT-PCR确认新冠肺炎状态为阳性或阴性，我们 将前瞻性地招募代表新冠肺炎疾病谱的新冠肺炎阳性患者(病例) 严重程度；我们将同时纳入住院的新冠肺炎阴性患者(对照)，按年龄、性别、 民族/种族、合并症和疾病严重程度。我们将使用序列多模式成像来表征 随着时间的推移，持续性心脏病与功能和结构恢复的轨迹。我们还将使用 先进的高通量质谱学方法来连续分析生物活性脂类二十烷类化合物，这些方法是 被认为是应激(包括)系统免疫炎症反应的上游分子介质 新冠肺炎)。我们将把二十烷类药物措施与感染后心脏病持续的轨迹联系起来。 对阵复苏。对于显著的关联，将检查按性别、年龄、 种族/民族、社会经济地位和宿主环境修饰者。

PROJECT SUMMARY Amidst the rapidly growing body of evidence regarding risks and outcomes associated with coronavirus disease 2019 (COVID-19), many knowledge gaps persist. We and others have reported on how certain comorbidities, including cardiovascular risk factors, predispose some individuals more than others to the severest forms of COVID-19 illness. The natural history, diversity, and determinants of end-organ sequelae following COVID-19 illness remain unknown. Extending beyond lung injury, accumulating data have highlighted not only short-term but also potentially long-term adverse effects involving the heart. In fact, multiple reports have indicated a high prevalence of subclinical as well as clinical abnormalities in cardiac structure and function seen among patients recovering from even mild cases of COVID-19 illness. Based on the emerging evidence and our own clinical experience to date, we hypothesize that SARS-Cov-2 provokes a systemic immune-inflammatory response that leads to under-recognized myocardial disease in a large proportion of infected individuals – in a manner that persists over time and represents elevated risk for the longer-term post-acute sequelae of COVID-19. Thus, we propose to expand the application of novel cardiac imaging methods to comprehensively characterize the post- infectious cardiac effects of COVID-19. Our specific aims are: (1) to identify and characterize the longitudinal trajectories of cardiac disease and associated outcomes following the post-acute phase of COVID-19 illness; and, (2) to characterize the longitudinal trajectories of immune-inflammatory response to COVID-19 illness, and their relations with post-infectious cardiac disease and associated outcomes. From our growing source sample of >12,500 hospitalized treated since 3/8/2020 for rt-PCR confirmed positive or negative COVID-19 status, we will prospectively enroll COVID-19 positive patients (cases) representing the spectrum of COVID-19 illness severity; we will simultaneously enroll hospitalized COVID-19 negative patients (controls) matched on age, sex, ethnicity/race, comorbidities, and illness severity. We will use serial multi-modality imaging to characterize trajectories of persistent cardiac disease versus functional and structural recovery over time. We will also use advanced high-throughput mass spectrometry methods to serially profile bioactive lipid eicosanoids, which are recognized as upstream molecular mediators of the systemic immune-inflammatory response to stress (including COVID-19). We will relate eicosanoid measures with trajectories of post-infectious cardiac disease persistence versus recovery. For significant associations, will examine heterogeneity in trajectories by sex, age, race/ethnicity, socioeconomic status, and host-environment modifiers.