Immunologic basis of cardiac disease after severe COVID-19

重症COVID-19后心脏病的免疫学基础

• 批准号: 10650182
• 负责人: Jason V Baker
• 金额: $ 68.5万
• 依托单位: UNIVERSITY OF MINNESOTA
• 依托单位国家: 美国
• 财政年份: 2022
• 资助国家: 美国
• 起止时间: 2022-07-01 至 2026-05-31
• 项目状态: 未结题
• 来源: https://reporter.nih.gov/project-details/10650182
• 关键词: 2019-nCoV; ACE2; Acute; Admission activity; Award; Biological Markers; Blood specimen; CD4 Positive T Lymphocytes; COVID-19; COVID-19 patient; COVID-19 survivors; Cardiac; Cardiology; Cardiomyopathies; Cardiopulmonary; Cardiovascular system; Cells; Chronic; Clinical; Communicable Diseases; Diffuse; Endothelial Cells; Epidemic; Epidemiology; Fibroblasts; Fibrosis; Frequencies; Functional disorder; Goals; Health; Heart Abnormalities; Heart Diseases; Heart Injuries; Hospitalization; Immune; Immune response; Immunofluorescence Immunologic; Immunologics; Immunology; In Vitro; Infection; Inflammation; Inflammatory; Influenza; Injury; Intervention; Knowledge; Late Effects; Life; Long COVID; Low Prevalence; Lymphopenia; Macrophage; Magnetic Resonance; Measures; Mediating; Microcirculation; Mononuclear; Muscle Cells; Myocardial; Myocardial dysfunction; Myocarditis; Natural Immunity; Organ; Participant; Pathology; Patients; Peptides; Pericytes; Phenotype; Post-Acute Sequelae of SARS-CoV-2 Infection; Proteins; Protocols documentation; Recovery; Reporting; Research; Respiratory Disease; Respiratory Failure; SARS-CoV-2 infection; Science; Specialist; Specimen; Survivors; Symptoms; T cell response; T-Lymphocyte; Testing; Tissues; Troponin; Viral; Virus Diseases; Work; adaptive immune response; cardiac magnetic resonance imaging; cardiovascular effects; cardiovascular injury; clinically relevant; cohort; coronary fibrosis; coronavirus disease; cytokine; disability; experience; heart damage; immune activation; improved; influenza infection; injured airway; lung failure; monocyte; myocardial injury; neutrophil; novel; pandemic disease; participant enrollment; particle; persistent symptom; receptor; response; risk stratification; severe COVID-19; spatial relationship; study population; systemic inflammatory response; thrombotic complications; wound healing; 2019-nCoV; ACE2; Acute; Admission activity; Award; Biological Markers; Blood specimen; CD4 Positive T Lymphocytes; COVID-19; COVID-19 patient; COVID-19 survivors; Cardiac; Cardiology; Cardiomyopathies; Cardiopulmonary; Cardiovascular system; Cells; Chronic; Clinical; Communicable Diseases; Diffuse; Endothelial Cells; Epidemic; Epidemiology; Fibroblasts; Fibrosis; Frequencies; Functional disorder; Goals; Health; Heart Abnormalities; Heart Diseases; Heart Injuries; Hospitalization; Immune; Immune response; Immunofluorescence Immunologic; Immunologics; Immunology; In Vitro; Infection; Inflammation; Inflammatory; Influenza; Injury; Intervention; Knowledge; Late Effects; Life; Long COVID; Low Prevalence; Lymphopenia; Macrophage; Magnetic Resonance; Measures; Mediating; Microcirculation; Mononuclear; Muscle Cells; Myocardial; Myocardial dysfunction; Myocarditis; Natural Immunity; Organ; Participant; Pathology; Patients; Peptides; Pericytes; Phenotype; Post-Acute Sequelae of SARS-CoV-2 Infection; Proteins; Protocols documentation; Recovery; Reporting; Research; Respiratory Disease; Respiratory Failure; SARS-CoV-2 infection; Science; Specialist; Specimen; Survivors; Symptoms; T cell response; T-Lymphocyte; Testing; Tissues; Troponin; Viral; Virus Diseases; Work; adaptive immune response; cardiac magnetic resonance imaging; cardiovascular effects; cardiovascular injury; clinically relevant; cohort; coronary fibrosis; coronavirus disease; cytokine; disability; experience; heart damage; immune activation; improved; influenza infection; injured airway; lung failure; monocyte; myocardial injury; neutrophil; novel; pandemic disease; participant enrollment; particle; persistent symptom; receptor; response; risk stratification; severe COVID-19; spatial relationship; study population; systemic inflammatory response; thrombotic complications; wound healing

ABSTRACT Coronavirus Disease 2019 (COVID-19) caused by Severe Acute Respiratory Syndrome Coronavirus 2 (SARS- CoV-2) has become a widespread global pandemic. While the predominant clinical manifestation of severe COVID-19 is respiratory failure, other organ complications such as cardiac injury are common. Cardiac injury and cardiomyopathy are frequent cardiac manifestations during acute illness. Additionally, some survivors of COVID-19 are experiencing cardiopulmonary symptoms months after the acute illness, referred to as Post- Acute Sequelae of SARS-CoV-2 (PASC) or “Long COVID”. Given the frequency of cardiovascular injury during COVID-19 and the persistence of symptoms for extended periods after the acute illness, there is an urgent need for studies of the late effects of SARS-CoV-2 on the cardiovascular system. We aim to investigate the central hypothesis that immune responses to severe COVID-19 cause acute inflammation and injury that result in clinically relevant myocardial fibrosis and dysfunction over the long-term. Since August 2020, we have been enrolling patients in a COVID-19 Immune Profiling (IP) Study, which includes a protocol to collect blood specimens from patients with COVID-19 at admission, during hospitalization, 1-3 months, and 3-12 months after recovery. We will co-enroll participants from this study and perform cardiac magnetic resonance imaging (CMR) and additional functional cardiopulmonary assessments at 3-12 months and 2-3 years after recovery. Our specific aims include, Aim 1) Identify innate immune profiles during severe COVID-19 that predict long- term cardiac damage. We will focus innate immunity measures in blood specimens collected at admission and early recovery, Aim 2) Establish whether adaptive immune responses contribute to cardiac injury after COVID- 19. We will quantify responses targeting SARS-CoV-2 as well as explore maladaptive responses targeting cardiac proteins. Analysis of blood specimens will be supplemented with exploratory studies of cardiac tissue, and Aim 3) Determine the long-term structural and functional cardiac abnormalities after severe COVID-19. This includes characterization of cardiac fibrosis and dysfunction, cardiopulmonary dysfunction, and clinical symptoms. Comparisons will be made with control participants who had influenza infection 1-2 years prior. Our proposal responds to urgent need for science characterizing long-term cardiac complications following COVID- 19. Our collaborative team has extensive experience spanning cardiology, infectious disease, immunology, and epidemiology, and will be led by a cardiologist with expertise in CMR and inflammatory cardiomyopathies, and an infectious diseases specialist with expertise in cardiovascular complications in the context of chronic viral infections. Successful completion of our work will help understand the long-term cardiovascular effects of severe COVID-19 illness. This knowledge could, in turn, help enhance health, lengthen life, and reduce illness and disability in COVID-19 survivors.

抽象的 由严重急性呼吸综合征冠状病毒2（SARS-- SARS- COV-2）已成为广泛的全球大流行。而重度的主要临床表现 COVID-19是呼吸衰竭，其他器官并发症（例如心脏损伤）很常见。心脏损伤 心肌病经常是急性疾病期间的心脏表现。另外，一些生存 COVID-19发生急性疾病几个月后的心肺症状，被称为 SARS-COV-2（PASC）或“长卷”的急性后遗症。考虑到心血管损伤的频率 Covid-19和急性疾病后长时间症状的持久性，紧急 需要研究SARS-COV-2对心血管系统的晚期影响。我们旨在调查 中心假设，即对严重的covid-19的免疫反应会引起急性炎症和损伤，从而导致 长期内，在临床相关的心肌纤维化和功能障碍中。自2020年8月以来，我们一直 将患者招募参加COVID-19免疫分析（IP）研究，其中包括收集血液的方案 入院，住院期间，1-3个月和3-12个月的Covid-19患者的标本 恢复后。我们将从这项研究中共同摄取参与者，并进行心脏磁共振成像 （CMR）和恢复后2 - 3年的其他功能性心肺评估。 我们的具体目的包括，目标1）确定严重的COVID期间先天免疫特征，以预测长期 术语心脏损伤。我们将重点关注入院时收集的血液标本的先天免疫学指标 早期恢复，目标2）确定适应性免疫调查是否有助于偶然的心脏损伤 19.我们将量化针对SARS-COV-2的响应，并探索针对性的适应不良反应 心脏蛋白质。血液标本的分析将补充心脏组织的探索性研究， 目标3）确定严重的Covid-19之后的长期结构和功能性心脏异常。 这包括心脏纤维化和功能障碍，心肺功能障碍和临床表征 症状。比较将与1 - 2年前影响的对照参与者进行比较。我们的 提出对迫切需要科学需要的反应，以表征长期心脏并发症之后的长期心脏并发症 19。我们的协作团队拥有跨越心脏病，传染病，免疫学，免疫学的丰富经验 和流行病学，并将由CMR和炎症性心肌病专家的心脏病专家领导 以及具有慢性疾病专业知识的传染病专家 病毒感染。成功完成我们的工作将有助于了解 严重的covid-19疾病。这些知识反过来可以帮助增强健康，延长寿命并减少疾病 与19009年相冲浪者的残疾。