Autoimmune responses associated with SARS-CoV-2 infection

项目总结 目前的研究集中在新冠肺炎大流行的三个重要方面-治疗、疫苗和诊断。 指导UPMC临床免疫诊断实验室，我们了解启动临床的迫切需要 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 新冠肺炎患者。虽然强大的免疫反应与大多数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，病毒会传播，并大量 受影响的组织将被破坏。广泛的组织损伤和自身抗原的释放，特别是在 与不成比例的全身炎症和细胞因子风暴有关，已被证明调节失调 外周免疫耐受和促进自身免疫途径的启动。我们的工作假设是 新冠肺炎康复者发生自身抗原抗体的风险增加(S是高危人群) 风险假说具有重要的临床意义，将为未来的机制研究奠定基础。至 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通过测量有新冠肺炎感染史的患者中自身抗体的患病率来确定感染情况。如果我们的 假设得到证实，我们的数据将提供第一个证据，证明需要跟随新冠肺炎找回 患者出现自身免疫抗体并增加全身和组织特异性风险 自身免疫性疾病。

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.