Autoimmune responses associated with SARS-CoV-2 infection

与 SARS-CoV-2 感染相关的自身免疫反应

• 批准号: 10611414
• 负责人: Sarah E. Wheeler
• 金额: $ 19.88万
• 依托单位: UNIVERSITY OF PITTSBURGH AT PITTSBURGH
• 依托单位国家: 美国
• 财政年份: 2022
• 资助国家: 美国
• 起止时间: 2022-04-19 至 2025-03-31
• 项目状态: 未结题
• 来源: https://reporter.nih.gov/project-details/10611414
• 关键词: 2019-nCoV; Acute Respiratory Distress Syndrome; Affect; Age Years; Antibodies; Antibody Response; Antigens; Aplastic Anemia; Appearance; Attention; Autoantibodies; Autoantigens; Autoimmune; Autoimmune Diseases; Autoimmune Responses; Autoimmunity; Biological Assay; Biological Markers; CD4 Positive T Lymphocytes; CD8-Positive T-Lymphocytes; COVID-19; COVID-19 pandemic; COVID-19 patient; Cell Death; Cells; Child; Clinical; Clinical Research; Computerized Medical Record; Cost Savings; Data; Detection; Development; Diabetes Mellitus; Diagnosis; Diagnostic; Disease; Drug usage; Epitope spreading; Epstein-Barr Virus Infections; FDA approved; Future; Gender; Generations; Guillain Barré Syndrome; Health; Health Care Costs; Health Resources; Human Herpesvirus 4; Immune; Immune Tolerance; Immune response; Immune system; Immunodiagnostics; Impairment; Individual; Infection; Insurance Carriers; Laboratories; Lead; Measures; Mediating; Molecular Mimicry; Mucocutaneous Lymph Node Syndrome; Multiple Sclerosis; Nuclear Antigens; Outcome; Pathology; Pathway interactions; Patients; Pattern; Peripheral; Population; Predisposition; Prevalence; Prevention; Process; Public Health; Quality of life; Recording of previous events; Recovery; Research; Rheumatoid Arthritis; Risk; Role; SARS-CoV-2 infection; SARS-CoV-2 infection history; Sampling; Self Tolerance; Serum; Syndrome; Systemic Lupus Erythematosus; Systemic Scleroderma; Testing; Tissues; Vaccines; Viral; Viral Antigens; Virus; Virus Diseases; Vitiligo; Work; age group; autoimmune rheumatologic disease; clinical care; cohort; cytokine release syndrome; diagnostic assay; early detection biomarkers; follow-up; health care service utilization; high risk; immune activation; improved; long term consequences of COVID-19; post SARS-CoV-2 infection; pre-clinical; prevent; response; sample collection; severe COVID-19; side effect; standard of care; systemic autoimmune disease; systemic inflammatory response

PROJECT SUMMARY Current research focuses on three important aspects of COVID-19 pandemic – therapy, vaccine and diagnostics. Directing UPMC's Clinical Immune Diagnostic Laboratory, we understand the urgent need to initiate clinical research that will allow us to assess and analyze potential deferred health outcomes in a population of recovered COVID-19 patients. Although a robust immune response is associated with clinical recovery of most SARS-CoV- 2 infected patients, when a protective immune response is impaired or delayed, virus will propagate, and massive destruction of the affected tissues will occur. Extensive tissue damage and release of autoantigens, especially if associated with disproportionate systemic inflammation and cytokine storm, has been shown to dysregulate peripheral immune tolerance and facilitate initiation of autoimmune pathways. Our working hypothesis that COVID-19 recovered individuals are under increased risk of developing antibodies to self-antigen(s) is a high- risk hypothesis with important clinical implications that will lay the groundwork for future mechanistic studies. To test our hypothesis, we propose to: Determine if increased autoantibodies are associated with prior SARS-CoV- 2 infection by measuring prevalence of autoantibodies in patients with a history of COVID-19 infection. If our hypothesis is confirmed, our data will provide the first evidence for the need to follow COVID-19 recovered patients for the appearance of autoimmune antibodies and increased risk of systemic and tissue-specific autoimmune diseases.

项目摘要 当前的研究重点介绍了COVID-19大流行 - 治疗，疫苗和诊断的三个重要方面。 指导UPMC的临床免疫诊断实验室，我们了解迫切需要启动临床 将使我们能够评估和分析恢复人群中潜在的递延健康结果的研究 Covid-19患者。尽管强大的免疫响应与大多数SARS-COV的临床恢复有关 2例感染的患者，当受保护的免疫响应受损或延迟时，病毒将传播并大量 会破坏受影响的组织。广泛的组织损伤和自动抗原的释放，尤其是 与不成比例的全身感染和细胞因子风暴有关，已显示出失调 外周免疫公差和促进自身免疫途径的倡议。我们的工作假设是 COVID-19恢复的个体面临着开发自我抗原抗体的风险，是一种高 风险假设具有重要的临床意义，将为将来的机械研究奠定基础。到 检验我们的假设，我们建议：确定自身抗体增加是否与先前的SARS-COV相关 2通过测量具有COVID-19感染史的患者自身抗体的患病率来感染。如果我们 确认了假设，我们的数据将提供第一个证据，证明需要遵循COVID-19的恢复 患者出现自身免疫性抗体，并增加了系统性和组织特异性的风险 自身免疫性疾病。