Tulane University COVID Antibody and Immunity Network (TUCAIN)

总体摘要 据报道，新冠肺炎的病原体SARS-CoV-2病毒已在全球感染了13,810,247人 截至2020年7月16日，死亡率为4.2%。在路易斯安那州，超过7.3%的86,411新冠肺炎 病例涉及癌症患者。理论上，恢复期的血浆含有保护性抗体 中和病毒，减轻其致病作用。然而，我们对这一问题的理解仍有很大差距 驱动体液和细胞免疫反应的机制以及这些反应与疾病的关系 这些反应的方向和保护以及这些反应的持久性。此外，有必要进行血清学检查。 准确测量这些反应以进行血清学诊断以及作为免疫和保护的相关性的检测。 在没有这些知识的情况下，恢复期血浆治疗新冠肺炎和我们的 了解SARS-CoV-2的体液免疫反应，特别是免疫低下患者的体液免疫反应 仍将是未知的。 杜兰大学康复抗体和免疫网络(TUCAIN)的总体目标是 从功能和耐用性两个方面描述这种响应。我们将通过调查来实现这一目标 以下广泛的具体目标：(1)描述体液免疫的进化、功能和寿命 对新冠肺炎的回应。(2)识别有助于持久或短暂的细胞介导的免疫反应 对SARS CoV-2的体液免疫。(3)将保护性免疫反应和潜在的致病免疫反应关联起来 住院新冠肺炎患者的临床病程。我们将通过研究不同的 新冠肺炎幸存者和病情最轻的血清转换者，包括一大批恶性肿瘤患者。 利用系列血液采集，我们将应用几种免疫学技术来研究进化和 随着时间的推移，免疫反应的持久性。我们还将把这些反应与患者的预后联系起来 疾病发病机制采用“大数据”、系统生物学的方法。一种方法，比如我们提出的方法， 将使我们能够确定新冠肺炎幸存者是否形成了基于抗体的长期保护，我们可以 确认恢复期血浆是否具有治疗潜力。这项研究将使我们能够确定新的目标 药物和疫苗，为个性化治疗策略提供信息，如 免疫功能低下的癌症患者，并提供适用于广泛的新型免疫学算法 人类病原体的范围。

Overall Summary The SARS-CoV-2 virus, the causative agent of COVID-19, has infected a reported 13,810,247 persons globally as of July 16, 2020 with a mortality rate of 4.2%. In the State of Louisiana, over 7.3% of the 86,411 COVID-19 cases involve people living with cancer. Theoretically, convalescent plasma contains protective antibodies that neutralizes virus and mitigates its pathogenic effects. Yet, there remains a large gap in our understanding of the mechanisms that drive humoral and cellular immune responses and how these responses correlate with disease course and protection as well as the durability of those responses. Furthermore, there is a need for serological assays that measure these responses accurately for serodiagnosis and as correlates of immunity and protection. Without this knowledge, the true efficacy of convalescent plasma as therapy for COVID-19 and our understanding of the humoral immune response to SARS-CoV-2, especially in immunocompromised patients, will remain unknown. The overall goal of the Tulane University Convalescent Antibody and Immunity Network (TUCAIN) is to characterize this response with respect to functionality and durability. We will achieve this goal by investigating the following broad specific aims: (1) Characterize the evolution, function and longevity of the humoral immune response to COVID-19. (2) Identify cell mediated immune responses that contribute to durable or short-lived humoral immunity to SARS CoV-2. (3) Correlate protective and potentially pathogenic immune responses to the clinical course of hospitalized COVID-19 patients. We will achieve these goals by studying a diverse cohort of COVID-19 survivors and minimally sick seroconverters, including a large cohort of patients with malignancies. Using serial blood collections, we will apply several immunological technologies to study the evolution and durability of the immune response over time. We will also correlate these responses to patient outcomes and disease pathogenesis using a “big data”, systems biology approach. An approach, such as the one we propose, will allow us to determine if COVID-19 survivors develop long-term, antibody-based protection and we can confirm if convalescent plasma has therapeutic potential. This research will allow us to identify new targets for medicines and vaccines, inform personalized treatment strategies such as those required by immunocompromised patients with cancer, and to provide novel immunological algorithms applicable to a wide range of human pathogens.