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: 10373287
• 负责人: Sarah E. Wheeler
• 金额: $ 22.29万
• 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 2024-03-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/10373287
• 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; 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; 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; biomarker identification; case control; clinical care; cohort; cytokine release syndrome; diagnostic assay; early detection biomarkers; follow-up; health care service utilization; high risk; immune activation; 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 目前的研究集中在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负责人，我们了解开展临床免疫诊断的迫切需要。 这项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， 2019冠状病毒病患者。尽管强有力的免疫应答与大多数SARS-CoV的临床恢复有关， 2感染患者，当保护性免疫反应受损或延迟时，病毒将繁殖，并大量传播。 将发生受影响组织的破坏。广泛的组织损伤和自身抗原的释放，特别是如果 与不成比例的全身性炎症和细胞因子风暴有关， 外周免疫耐受和促进启动自身免疫途径。我们的假设是 COVID-19康复者产生自身抗原抗体的风险增加， 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。到 为了验证我们的假设，我们建议：确定增加的自身抗体是否与先前的SARS-CoV相关- 通过测量有COVID-19感染史的患者中自身抗体的患病率来评估2型感染。如果我们的 假设得到证实，我们的数据将为需要跟踪COVID-19恢复提供第一个证据 患者自身免疫抗体的出现以及全身性和组织特异性 自身免疫性疾病