Vulnerability of SARS- CoV-2 Infection in Lung Cancer Based on Serological Antibody Analyses

总体摘要 西奈山U 54血清学卓越中心的首要研究主题是“脆弱性”， SARS-CoV-2感染肺癌的血清学抗体分析》是填补 导致肺癌患者对SARS发病率和死亡率的巨大脆弱性的因素的差距- 通过抗体应答的血清学分析和CoV-2感染个体间变异的研究， 患者来源的肺肿瘤和上皮细胞对SARS-CoV-2的感染。我们将描述和比较肺 癌症患者对SARS-CoV-2感染或SARS-CoV-2疫苗的抗体应答， 肺癌对照组;肺癌和正常肺中SARS-CoV-2病毒复制的定量差异 来自不同肺癌患者的上皮细胞;并定量中和抗体应答的差异 在肺癌患者中。迫切需要这些信息来制定疫苗和其他保护战略。 肺癌患者预防COVID-19的发展。而由感染或疫苗诱导的抗体， 对许多病毒的保护，尚未确定SARS-CoV-2的抗体是否具有保护作用，如何保护？ 保护所需的抗体数量和类型，以及保护能持续多久都是未知数。 同样，我们不知道肺癌患者是否能产生有效的免疫反应， 肺癌或其治疗会影响这种免疫反应。我们的总体假设是肺癌 患者有不同的（e. G.较弱）的抗体反应SARS-CoV-2感染相比，没有人 肺癌，并且他们的肺癌或肺上皮细胞在宿主反应的病毒复制中起作用， 这些共同解释了肺癌患者的侵袭过程和高死亡率 新冠肺炎我们的U 54将决定是否自然感染或SARS-CoV-2疫苗（预测为 部署）将在1，000名肺癌患者中纵向提供可比较的血清学抗体应答 和匹配的非肺癌对照组（1，000人）;并确定是否存在差异 抗体应答与年龄、性别、吸烟史和人种/种族有关。U 54提案有两个 项目和三个核心（行政、临床和数据科学）。项目1：“确定 肺癌患者对SARS-CoV-2的抗体应答”定量表征抗SARS-CoV-2 与对照人群相比，肺癌患者的抗体应答及其功能性 在自然感染和疫苗接种后，并将血清学应答特征与关键临床， 人口统计信息。项目2：“肺癌细胞对SARS-CoV-2感染和抗体的易感性- 介导的中和”决定了肺癌和肺上皮细胞的个体间差异， 支持SARS-CoV-2病毒复制，中和病毒感染的抗体的个体间变异， 这些宿主病毒应答与宿主细胞特征和重要临床人口统计学信息的关系。

OVERALL ABSTRACT The overarching research theme for the Mount Sinai U54 Serological Center of Excellence “Vulnerability of SARS-CoV-2 Infection in Lung Cancer Based on Serological Antibody Analyses,” is to fill the vital knowledge gap in factors contributing to the great vulnerability of lung cancer patients to morbidity and mortality from SARS- CoV-2 infection through serological analysis of antibody responses and studies of inter-individual variation in patient-derived lung tumor and epithelial cells to SARS-CoV-2 infection. We will characterize and compare lung cancer patients’ antibody responses to SARS-CoV-2 infection or SARS-CoV-2 vaccines with a matched non- lung cancer control group; quantitate differences in SARS-CoV-2 viral replication in lung cancer and normal lung epithelial cells from different lung cancer patients; and quantitate differences in neutralizing antibody responses in lung cancer patients. This information is urgently needed to enact vaccine and other strategies for protecting lung cancer patients against development of COVID-19. While antibodies, induced by infection or vaccines, are protective against many viruses, it has not yet been established if antibodies to SARS-CoV-2 are protective, how much and what types of antibody are needed for protection, and how long protection will last are unknown. Likewise, we do not know if lung cancer patients can mount an effective immune response and if different aspects of lung cancer or its treatment influences this immune response. Our overall hypothesis is that lung cancer patients have a different (e. g. weaker) antibody response to SARS-CoV-2 infection compared to persons without lung cancer, and that their lung cancer or lung epithelial cells play a role in viral replication of host responses, which together could explain the aggressive course and high fatality rate demonstrated in lung cancer patients with COVID-19. Our U54 will determine whether natural infection or SARS-CoV-2 vaccines (forecast for deployment) will give comparable serological antibody responses longitudinally in 1,000 lung cancer patients and a matched non-lung cancer control group (1,000 individuals); and determine if there are differences in antibody responses related to age, gender, tobacco history, and race/ethnicity. The U54 proposal has two Projects and three Cores (Administrative, Clinical, and Data Sciences). Project 1: “Characterization of the Antibody Response to SARS-CoV-2 in Lung Cancer Patients” quantitatively characterizes anti-SARs-CoV-2 antibody responses and their functionality longitudinally in lung cancer patients compared to a control population after natural infection and vaccination, and relates the serological response characteristics to key clinical, demographic information. Project 2: “Susceptibility of Lung Cancer Cells to SARS-CoV-2 Infection and Antibody- Mediated Neutralization,” determines the inter-individual variation in lung cancers and lung epithelial cells to support SARS-CoV-2 viral replication, the inter-individual variation of antibodies to neutralize viral infection, and how these host viral responses relate to host cell characteristics and important clinical demographic information.