Immuno-Serological Assays for Monitoring COVID19 in Patients with Hematologic Malignancies

总结 血液恶性肿瘤患者似乎有更高的SARS-CoV-2感染风险。疾病 病程的严重程度不同，受恶性肿瘤及其治疗引起的免疫抑制的影响 确定与肺损伤，多器官衰竭， 与死这凸显了对全面临床测试的需求，以监测COVID 19患者，特别是， 血液恶性肿瘤我们建议开发和验证两种新的免疫血清学检测方法， 将部署进行血浆标记物和外周血免疫细胞的纵向测量 不同血液系统恶性肿瘤的新冠肺炎患者。首先，我们将开发一个自动化的32路 定量SARS-COV-2 IgG/IgM抗体、细胞因子/趋化因子、血管生成的血浆蛋白测定 标记物、内皮病标记物和促血栓形成标记物全部组合在高密度抗体中 条形码阵列微芯片。第二，我们将开发一种微芯片检测单细胞免疫功能 测量以定量外周血中的细胞类型和30+免疫效应蛋白， 患者将对选定样本进行单细胞转录组测序，以交叉验证结果 并揭示COVID诱导的免疫激活的作用机制。第三，这些新的分析将是 用于测量一组患有或不患有血液恶性肿瘤的COVID 19患者和健康 以确定与免疫介导的病理学和COVID疾病的潜在分子相关性 严重程度在血液癌症患者中独一无二。随着COVID-19疫苗的上市，我们将申请 这些检测用于监测疫苗诱导的体液、细胞和免疫应答， 癌症患者，并与非癌症人群进行比较，以了解差异和改善 血液恶性肿瘤患者的疫苗接种成功-一个可能不需要接种疫苗的脆弱患者群体 遵循与COVID 19中一般人群相同的机制。

SUMMARY Patients with hematologic malignancies appear to have a higher risk of SARS-CoV-2 infection. Disease courses are variable in severity, influenced by immunosuppression due to the malignancy and its treatment determining the degree of immune-mediated hyperinflammation implicated in lung damage, multi-organ failure, and death. This highlights the need for comprehensive clinical tests to monitor COVID19 patients, specifically, with hematologic malignancies. We propose to develop and validate two novel immuno-serological assays that will be deployed to conduct longitudinal measurement of plasma markers and peripheral blood immune cells from COVID patients with different hematologic malignancies. First, we will develop an automated 32-plexed plasma protein assay to quantify SARS-COV-2 IgG/IgM antibodies, cytokines/chemokines, angiogenesis markers, endotheliopathy markers, and pro-thrombotic markers all combined in a high-density antibody barcode array microchip. Second, we will develop a microchip assay for single-cell immune function measurement to quantify cell types and 30+ immune effector proteins in peripheral blood immune from patients. Single-cell transcriptome sequencing will be performed on select samples to cross-validate the results and reveal the mechanisms of action in COVID-induced immune activation. Third, these new assays will be deployed to measure a cohort of COVID19 patients with or without hematological malignancies and healthy donors in order to identify potential molecular correlates with immune-mediated pathology and COVID disease severity uniquely in hematological cancer patients. As the COVID19 vaccines become available, we will apply these assays to monitoring vaccine-induced humoral, cellular, and immunological response in hematological cancer patients and compare to non-cancer populations to understand differences and ways to improve the success of vaccination in patients with hematologic malignancies – a vulnerable group of patients who may not follow the same mechanisms as general populations in COVID19.