COVID-19 Lung Microvascular and Parenchymal Sequelae (Lung-MaPS)

新冠肺炎对健康的长期影响仍不确定。我们已经在提供住院后治疗 纽约哥伦比亚大学欧文医疗中心为数以千计的新冠肺炎幸存者提供关怀 城市。这项研究旨在帮助我们和其他医疗中心通过使用黄金- 描述严重新冠肺炎主要后遗症的标准成像方法。是否有可能 严重新冠肺炎的显著血管和实质后遗症是由突出的肺泡- 临床观察的动脉梯度，加上组织病理学证实的实质内皮细胞和上皮细胞 损坏。然而，对体内血管和实质后遗症的准确评估一直是有限的， 尤其是对于血管系统，缺乏长期的随访来评估恢复或进展。我们的 调查小组开发和改进了一种双能量计算机断层扫描(CT)方案，以提供 肺血管系统的直接测量，包括肺实质灌注量 (PBV)；以及，实质的详细表型，包括毛玻璃不透明(GGO)纹理，我们 在新冠肺炎的初步工作中，通过自适应多要素模型方法确定了 幸存者。在多种族队列研究中，我们将这些CT测量与发育和 慢性肺部疾病的进展。加强我们对潜在微血管机制的研究 对于新冠肺炎肺损伤，这一应用还将测试PBV是否与炎症的生物标志物有关， 高凝状态和补体激活。我们将随机抽样200名没有事先诊断的成年人 因新冠肺炎在中大集团住院且不需要插管的慢性肺部疾病患者，外加100% 血清阴性对照在年龄、性别、种族、种族、体重指数和邻里关系上匹配。全 参与者将接受增强的双能量CT，即肺对碳的弥散能力 一氧化碳、肺活量测定、问卷调查和采血检测SARS-CoV-2抗体和生物标志物。这些 措施将在出院后3-12个月和27-36个月执行，以完成 三个具体目标。目的1明确新冠肺炎的肺微血管后遗症。我们假设PBV在 新冠肺炎幸存者的基因将更低，更具异质性，这些异常将与 检测IL-6、C反应蛋白、D-二聚体、C5a、MBL、MASP-2水平。目的2是为了定义肺实质后遗症 新冠肺炎。我们假设新冠肺炎幸存者身上会有更多的GGO纹理图案。目标3是 探讨与COVID相关的肺结构和促凝血生物标志物的差异是否保持在3 在急性疾病之后的几年。我们假设在基线研究访问后的两年内，实质和 生物标志物异常将恢复正常，但血管异常将继续发展。目标的实现 将指导COVID后护理和风险分层，建议治疗干预目标，并告知 新冠肺炎时代的风险缓解和公共卫生政策。

The long-term health impact of COVID-19 remains uncertain. We are already providing post-hospitalization care for thousands of COVID-19 survivors at Columbia University Irving Medical Center (CUIMC) in New York City. This study is designed to help our and other medical centers care for COVID-19 survivors by using gold- standard imaging approaches to describe the major sequelae of severe COVID-19. The possibility of significant vascular and parenchymal sequelae of severe COVID-19 is suggested by the prominent Alverolar- arterial gradients observed clinically, plus histopathology confirming substantial endothelial and epithelial damage. Nonetheless, precise assessments of vascular and parenchymal sequelae in vivo have been limited, especially for the vasculature, and long-term follow-up to assess recovery or progression is lacking. Our investigative team has developed and refined a dual-energy computed tomography (CT) protocol to provide direct measures of the pulmonary vasculature, including pulmonary parenchymal perfused blood volume (PBV); and, detailed phenotyping of the parenchyma, including ground glass opacity (GGO) textures, which we have identified by an adaptive multiple features model (AMFM) approach in preliminary work among COVID-19 survivors. In multiethnic cohort studies, we have associated these CT measures with development and progression of chronic lung diseases. To strengthen our investigation into potential microvascular mechanisms of COVID-19 lung injury, this application will also test if PBV is associated with biomarkers of inflammation, hypercoagulability, and complement activation. We will randomly sample 200 adults without a prior diagnosis of chronic lung disease who were hospitalized for COVID-19 at CUIMC and did not require intubation, plus 100 seronegative controls matched on age, sex, race, ethnicity, body mass index, and neighborhood. All participants will undergo contrast-enhanced dual-energy CT, diffusing capacity of the lung for carbon monoxide, spirometry, questionnaires, and phlebotomy for SARS-CoV-2 antibodies and biomarkers. These measures will be performed 3-12 months and 27-36 months post-COVID hospital discharge to accomplish three specific aims. Aim 1 is to define lung microvascular sequelae of COVID-19. We hypothesize that PBV in COVID-19 survivors will be lower and more heterogeneous, and that these abnormalities will be associated with levels of IL-6, CRP, d-dimer, C5a, MBL, and MASP-2. Aim 2 is to define lung parenchymal sequelae of COVID-19. We hypothesize that there will be greater GGO texture patterns in COVID-19 survivors. Aim 3 is to explore if COVID-related differences in lung structure and procoagulant biomarkers are maintained up to 3 years after acute illness. We hypothesize that two years following the baseline study visit, parenchymal and biomarker abnormalities will normalize, but vascular abnormalities will progress. Accomplishment of the Aims will guide post-COVID care and risk stratification, suggest targets for therapeutic interventions, and inform policies for risk mitigation and public health in the COVID-19 era.