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

COVID-19 肺微血管和实质后遗症 (Lung-MaPS)

• 批准号: 10614017
• 负责人: Elizabeth Oelsner
• 金额: $ 69.12万
• 依托单位: COLUMBIA UNIVERSITY HEALTH SCIENCES
• 依托单位国家: 美国
• 财政年份: 2021
• 资助国家: 美国
• 起止时间: 2021-07-15 至 2025-04-30
• 项目状态: 未结题
• 来源: https://reporter.nih.gov/project-details/10614017
• 关键词: 2019-nCoV; Acute; Adult; Age; Alveolar; Biological Markers; Blood Vessels; Blood Volume; Blood capillaries; Body mass index; C-reactive protein; COVID-19; COVID-19 impact; COVID-19 mortality; COVID-19 survivors; Carbon Monoxide; Caring; Cessation of life; Chronic lung disease; Clinical; Cohort Studies; Complement; Complement 5a; Complement Activation; Critical Care; Defect; Deposition; Development; Diagnosis; Diffuse; Diffusion; Endothelial Cells; Endothelium; Epithelial Cells; Epithelium; Ethnic Origin; Etiology; Fibrin fragment D; Fibrosis; Glass; Health; Heterogeneity; Histopathology; Hospitalization; Hospitals; Hypoxemia; Image; Infiltration; Inflammation; Inpatients; Interleukin-6; Intubation; Investigation; Longterm Follow-up; Lung; Lung Capacity; Measurement; Measures; Mechanical ventilation; Medical center; Modeling; Neighborhoods; New York City; Participant; Patients; Pattern; Perfusion; Phenotype; Policies; Prognosis; Protocols documentation; Public Health; Pulmonary Emphysema; Questionnaires; Race; Recording of previous events; Recovery; Regional Perfusion; Residual state; SARS-CoV-2 antibody; Sampling; Spirometry; Structure; Testing; Texture; Therapeutic Intervention; Thrombophilia; Thrombus; Universities; Venous blood sampling; Visit; Work; X-Ray Computed Tomography; angiogenesis; blood perfusion; cell injury; clinical care; complement pathway; contrast enhanced; coronavirus disease; design; experience; follow-up; imaging approach; improved; in vivo; innovation; insight; lung imaging; lung injury; multi-ethnic; post-COVID-19; posthospitalization care; prognostic; risk mitigation; risk stratification; severe COVID-19; sex; targeted treatment; vascular abnormality

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.

COVID-19对健康的长期影响仍不明朗。我们已经在提供住院后 在纽约的哥伦比亚大学欧文医疗中心（CUIMC）护理数千名COVID-19幸存者 市这项研究旨在帮助我们和其他医疗中心通过使用黄金来照顾COVID-19幸存者， 描述严重COVID-19主要后遗症的标准成像方法。的可能性 严重的COVID-19的显著血管和实质后遗症由突出的肺泡- 临床观察到的动脉压差，加上组织病理学证实大量内皮和上皮细胞 损害尽管如此，体内血管和实质后遗症的精确评估仍然有限， 特别是对于脉管系统，并且缺乏评估恢复或进展的长期随访。我们 一个研究小组已经开发并完善了一种双能量计算机断层扫描（CT）协议， 直接测量肺血管，包括肺实质灌注血容量 (PBV)以及，实质的详细表型，包括毛玻璃样混浊（GGO）纹理，我们 在COVID-19的初步工作中， 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。为了加强我们对潜在微血管机制的研究 对于COVID-19肺损伤，该应用程序还将测试PBV是否与炎症生物标志物相关， 高凝状态和补体激活。我们将随机抽取200名未经诊断的成年人 在CUIMC因COVID-19住院且不需要插管的慢性肺病患者，加上100 在年龄、性别、人种、种族、体重指数和邻居方面匹配的血清阴性对照。所有 参与者将接受对比增强双能量CT，肺碳弥散量 一氧化碳、肺量测定、问卷调查和抽血检查SARS-CoV-2抗体和生物标志物。这些 将在COVID出院后3-12个月和27-36个月采取措施， 三个具体目标。目的1是定义COVID-19的肺微血管后遗症。我们假设PBV在 COVID-19幸存者将更低，更异质，这些异常将与 IL-6、CRP、d-二聚体、C5 a、MBL和MASP-2水平。目的2是确定肺实质后遗症 2019冠状病毒病。我们假设在COVID-19幸存者中会有更大的GGO纹理模式。目标3是 探索与COVID相关的肺结构和促凝血生物标志物差异是否维持在3 几年后，急性病。我们假设在基线研究访视后两年， 生物标志物异常将正常化，但血管异常将进展。实现目标 将指导COVID后护理和风险分层，建议治疗干预的目标，并告知 在COVID-19时代降低风险和公共卫生的政策。