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: 10442251
• 负责人: Jason V Baker
• 金额: $ 69.46万
• 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/10442251
• 关键词: 2019-nCoV; 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; Enrollment; 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; 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; base; 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; macrophage; monocyte; myocardial injury; neutrophil; novel; pandemic disease; 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 由严重急性呼吸系统综合症冠状病毒 2 (SARS- CoV-2）已成为一种广泛的全球流行病，而其主要临床表现是严重的。 COVID-19是呼吸衰竭，心脏损伤等其他器官并发症也很常见。 心肌病是急性疾病期间常见的心脏表现。 COVID-19 在急性疾病发生几个月后出现心肺症状，称为“后- SARS-CoV-2 (PASC) 或“长期新冠病毒”的急性后遗症 考虑到心血管损伤的频率。 COVID-19 以及急性疾病后症状持续较长时间，有紧急情况 需要研究 SARS-CoV-2 对心血管系统的后期影响。 中心假设是，对严重 COVID-19 的免疫反应会导致急性炎症和损伤 自 2020 年 8 月以来，我们一直致力于临床相关的心肌纤维化和功能障碍的研究。 招募患者参加 COVID-19 免疫分析 (IP) 研究，其中包括采集血液的方案 COVID-19 患者入院时、住院期间、1-3 个月和 3-12 个月的标本 康复后，我们将共同招募本研究的参与者并进行心脏磁共振成像。 (CMR) 以及恢复后 3-12 个月和 2-3 年的其他功能性心肺评估。 我们的具体目标包括： 目标 1) 识别严重 COVID-19 期间的先天免疫特征，预测长期 我们将重点关注入院时收集的血液样本中的先天免疫措施。 早期恢复，目标 2) 确定适应性免疫反应是否会导致新冠肺炎后的心脏损伤 19. 我们将量化针对 SARS-CoV-2 的应对措施，并探索针对 心脏蛋白质的分析将辅以心脏组织的探索性研究， 目标 3) 确定严重 COVID-19 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的特征 我们将与 1-2 年前感染过流感的对照参与者进行比较。 该提案响应了对新冠病毒后长期心脏并发症的科学表征的迫切需求 19. 我们的合作团队在心脏病学、传染病、免疫学、 和流行病学，并将由具有 CMR 和炎症性心肌病专业知识的心脏病专家领导， 以及一位在慢性病心血管并发症方面具有专业知识的传染病专家 病毒感染的成功完成将有助于了解病毒感染对心血管的长期影响。 这些知识反过来又可以帮助增强健康、延长寿命并减少疾病。 以及 COVID-19 幸存者的残疾。