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.

项目概要 目前的研究重点是 COVID-19 大流行的三个重要方面——治疗、疫苗和诊断。 作为 UPMC 临床免疫诊断实验室的指导，我们了解启动临床免疫诊断的迫切需要 研究将使我们能够评估和分析康复人群中潜在的延迟健康结果 尽管强劲的免疫反应与大多数 SARS-CoV 的临床康复有关，但 COVID-19 患者。 2 感染患者，当保护性免疫反应受损或延迟时，病毒就会传播，并大规模传播 受影响的组织将发生广泛的组织损伤和自身抗原的释放，尤其是在这种情况下。 与不成比例的全身炎症和细胞因子风暴相关，已被证明会失调 我们的工作假设是，外周免疫耐受并促进自身免疫途径的启动。 COVID-19 康复者产生自身抗原抗体的风险增加，这是一个高风险因素。 具有重要临床意义的风险假设，将为未来的机制研究奠定基础。 检验我们的假设，我们建议：确定自身抗体增加是否与之前的 SARS-CoV-相关 通过测量有 COVID-19 感染史的患者中自身抗体的流行率来确定 2 感染情况。 假设得到证实，我们的数据将为需要跟踪 COVID-19 康复提供第一个证据 患者出现自身免疫抗体以及全身和组织特异性风险增加 自身免疫性疾病。