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: 10448304
• 负责人: Elizabeth Oelsner
• 金额: $ 70.75万
• 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/10448304
• 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; Epithelial Cells; Ethnic Origin; Etiology; Fibrin fragment D; Fibrosis; Follow-Up Studies; Glass; Gold; Health; Heterogeneity; Histopathology; Hospitalization; Hospitals; Hypoxemia; Image; Inflammation; Inpatients; Interleukin-6; Intubation; Investigation; Longterm Follow-up; Lung; Lung Capacity; Maps; 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; Residual state; SARS-CoV-2 antibody; Sampling; Spirometry; Structure; Testing; Texture; Therapeutic Intervention; Thrombophilia; Universities; Venous blood sampling; Visit; Work; X-Ray Computed Tomography; angiogenesis; cell injury; clinical care; complement pathway; contrast enhanced; coronavirus disease; design; experience; 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的长期健康影响仍然不确定。我们已经在提供院后 在纽约哥伦比亚大学欧文医学中心（CUIMC）的成千上万的共同18岁的幸存者照顾 城市。这项研究旨在通过使用金 - 标准成像方法描述了严重的covid-19的主要后遗症。可能的可能性 严重的COVID-19的显着血管和实质后遗症由明显的Alverolar-提示 在临床上观察到的动脉梯度，以及组织病理学确认了大量内皮和上皮 损害。但是，体内血管和实质后遗症的精确评估受到限制， 特别是对于脉管系统，缺乏评估恢复或进展的长期随访。我们的 调查团队已经开发并完善了双能计算机断层扫描（CT）协议，以提供 肺脉管系统的直接测量，包括肺实质血容量 （PBV）;以及详细的实质表型，包括地面玻璃不透明度（GGO）纹理，我们 通过自适应多元特征模型（AMFM）在Covid-19中的初步工作中确定 幸存者。在多民族队列研究中，我们将这些CT措施与开发和 慢性肺部疾病的进展。加强我们对潜在微血管机制的研究 在Covid-19-19肺损伤中，该应用还将测试PBV是否与炎症的生物标志物有关 高凝性和补体激活。我们将随机采样200名没有事先诊断的成年人 慢性肺疾病，在CUIMC住院，不需要插管，再加上100 血清调节控制与年龄，性别，种族，种族，体重指数和邻里相匹配。全部 参与者将经历对比增强的双能CT，肺部肺的扩散能力 SARS-COV-2抗体和生物标志物的一氧化碳，肺活量测定法，问卷和静脉切开术。这些 措施将在休息后出院后3-12个月零27-36个月进行 三个具体目标。目的1是定义COVID-19的肺微血管后遗症。我们假设该PBV 共vid-19的幸存者将较低，更异质，并且这些异常将与众不同 IL-6，CRP，D-二聚体，C5A，MBL和MASP-2水平。目标2是定义肺​​实质后遗症 新冠肺炎。我们假设Covid-19幸存者将有更大的GGO纹理模式。目标3是 探索肺结构和引发生物标志物的共同相关差异是否保持在3 急性疾病几年。我们假设在基线研究访问后两年，实质和 生物标志物异常将标准化，但血管异常将进展。实现目标 将指导后循环后的护理和风险分层，提出治疗干预措施的目标，并告知 COVID-19时代的降低风险和公共卫生的政策。