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

项目摘要 在有关冠状病毒疾病相关风险和结果的证据迅速增加的情况下， 2019年（COVID-19），许多知识差距仍然存在。我们和其他人已经报道了某些合并症， 包括心血管危险因素，使一些人比其他人更容易患上最严重的疾病。 COVID-19疾病。COVID-19后终末器官后遗症的自然史、多样性和决定因素 疾病仍然未知。除了肺损伤之外，积累的数据不仅强调了短期的 还可能对心脏造成长期的不良影响。事实上，多份报告显示， 在患者中观察到的心脏结构和功能亚临床和临床异常的患病率 从轻微的COVID-19疾病中恢复过来。根据新出现的证据和我们自己的临床 根据迄今为止的经验，我们假设SARS-Cov-2引起全身免疫炎症反应， 导致大部分受感染个体的心肌疾病未被充分认识， 随着时间的推移持续存在，并代表COVID-19长期急性后遗症的风险增加。因此我们 建议扩大新的心脏成像方法的应用，以全面表征术后 COVID-19对心脏的影响我们的具体目标是：（1）识别和表征纵向 COVID-19疾病急性期后的心脏病轨迹和相关结果; 以及，（2）表征对COVID-19疾病的免疫炎症反应的纵向轨迹，以及 它们与感染后心脏病的关系及相关结果。从我们不断增长的源样本中 自2020年3月8日以来，超过12，500名因rt-PCR确诊的COVID-19阳性或阴性状态而住院治疗的患者中，我们 将前瞻性招募代表COVID-19疾病谱的COVID-19阳性患者（病例） 严重程度;我们将同时招募年龄，性别， 种族/人种、合并症和疾病严重程度。我们将使用系列多模态成像来表征 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 先进的高通量质谱方法来连续分析生物活性脂质类花生酸， 被认为是对应激的系统性免疫炎症反应的上游分子介质（包括 COVID-19）。我们将把类花生酸测量与感染后心脏病持续性的轨迹联系起来， 与康复的对比对于显著相关性，将按性别、年龄、 种族/民族，社会经济地位和宿主环境修饰符。

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.