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

基于血清学抗体分析的 SARS-CoV-2 感染对肺癌的脆弱性

• 批准号: 10222305
• 负责人: Adolfo Garcia-Sastre
• 金额: $ 396.84万
• 依托单位: ICAHN SCHOOL OF MEDICINE AT MOUNT SINAI
• 依托单位国家: 美国
• 财政年份: 2020
• 资助国家: 美国
• 起止时间: 2020-09-30 至 2022-08-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/10222305
• 关键词: 2019-nCoV; Adult; Advocate; Age; Aggressive course; Antibodies; Antibody Response; Bioinformatics; Biology; Biometry; Budgets; COVID-19; COVID-19 vaccine; Cancer Patient; Cardiopulmonary; Cells; Characteristics; Clinical; Clinical Sciences; Clinical Trials; Complement; Contracts; Control Groups; Cytoprotection; Data Science; Data Science Core; Databases; Demographic Factors; Development; Disease; Doctor of Philosophy; Epithelial Cells; Ethnic Origin; Fatality rate; Gender; Histology; Immune; Immune response; Incidence; Individual; Infection; Informatics; Kinetics; Knowledge; Longevity; Lung; Lung Neoplasms; Lung infections; Malignant Neoplasms; Malignant neoplasm of lung; Mediating; Morbidity - disease rate; Normal tissue morphology; Patient Recruitments; Patients; Persons; Play; Population Control; Predisposition; Race; Recording of previous events; Research; Risk Factors; Role; Science; Serological; Seroprevalences; Smoking; Smoking History; Tobacco; Vaccination; Vaccines; Viral; Viral Load result; Virus; Virus Diseases; Virus Replication; base; cancer cell; cancer therapy; cigarette smoking; comorbidity; data dissemination; human subject; inter-individual variation; member; mortality; multidisciplinary; neoplastic cell; neutralizing antibody; patient population; programs; protective efficacy; response; sample collection; tumor; vaccine trial

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.

总体摘要 西奈山U54血清学卓越中心的首要研究主题是 基于血清抗体分析的SARS-CoV-2感染在肺癌中的应用 导致肺癌患者极易受到SARS发病率和死亡率影响的因素存在差距-- 冠状病毒2型感染的抗体反应血清学分析及个体间变异研究 患者来源的肺肿瘤和上皮细胞对SARS-CoV-2的感染。我们将对肺进行定性和比较 癌症患者对SARS-CoV-2感染或SARS-CoV-2疫苗与非匹配疫苗的抗体应答 肺癌对照组；定量检测肺癌与正常肺组织中SARS-CoV-2病毒复制的差异 来自不同肺癌患者的上皮细胞；并量化中和抗体反应的差异 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 肺癌患者不利于新冠肺炎的发展。而由感染或疫苗诱导的抗体是 对许多病毒具有保护作用，目前还没有确定SARS-CoV-2抗体是否具有保护作用，如何 目前尚不清楚需要多少抗体以及需要哪些类型的抗体来保护，以及保护能持续多久。 同样，我们不知道肺癌患者是否能产生有效的免疫反应，以及是否有不同的方面 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 与非患者相比，患者对SARS-CoV-2感染的抗体反应不同(例如较弱)。 肺癌，以及他们的肺癌或肺上皮细胞在宿主反应的病毒复制中发挥作用， 这些共同解释了肺癌患者表现出的侵袭性病程和高死亡率。 还有新冠肺炎。我们的U54将决定是自然感染还是SARS-CoV-2疫苗(预测 部署)将在1,000名肺癌患者中纵向产生类似的血清抗体反应 和匹配的非肺癌对照组(1000人)；并确定在 抗体反应与年龄、性别、吸烟史和种族/民族有关。U54提案有两个 项目和三个核心(管理、临床和数据科学)。项目1：“描述 肺癌患者对SARS-CoV-2的抗体应答“定量表征抗SARS-CoV-2 肺癌患者与对照人群纵向抗体应答及其功能的比较 在自然感染和接种疫苗后，并将血清学反应特征与关键临床相关联， 人口统计信息。项目二：肺癌细胞对SARS-CoV-2感染的易感性和抗体- 决定肺癌和肺上皮细胞的个体间变异 支持SARS-CoV-2病毒复制，即抗体的个体间变异，以中和病毒感染，以及 这些宿主病毒反应如何与宿主细胞特征和重要的临床人口统计信息相关。