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.

总体抽象 西奈山U54卓越血清学中心的总体研究主题 基于血清学抗体分析的肺癌中的SARS-COV-2感染是为了填补重要知识 因素的差距导致肺癌患者对SARS-的发病率和死亡率的极大脆弱性 COV-2通过血清学分析抗体反应的血清学分析和研究中个体差异的研究 患者衍生的肺肿瘤和上皮细胞至SARS-COV-2感染。我们将表征和比较肺 癌症患者对SARS-COV-2感染或SARS-COV-2疫苗的抗体反应与匹配的非 - 肺癌对照组；定量肺癌和正常肺中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。迫切需要此信息来制定疫苗和其他保护策略 肺癌患者反对开发Covid-19。虽然由感染或疫苗诱导的抗体是 保护许多病毒，如果保护了SARS-COV-2的抗体，它尚未建立 保护需要多种类型的抗体来保护，以及持续多长时间的保护是未知的。 同样，我们不知道肺癌患者是否可以安装有效的免疫响应和不同方面 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 与没有的人相比，患者对SARS-COV-2感染的抗体反应不同 肺癌，其肺癌或肺上皮细胞在宿主反应的病毒复制中起作用， 这可以解释肺癌患者表现出的侵略性病程和高死亡率 与Covid-19。我们的U54将确定自然感染还是SARS-COV-2疫苗（预测 部署）将在1,000名肺癌患者中纵向提供可比的血清学抗体反应 以及匹配的非肺癌对照组（1,000个个体）；并确定是否存在差异 抗体反应与年龄，性别，烟草历史和种族/种族有关。 U54提案有两个 项目和三个核心（行政，临床和数据科学）。项目1：“表征 肺癌患者对SARS-COV-2的抗体反应”定量表征了抗SARS-COV-2 与对照人群相比 自然感染和疫苗接种后，将血清学反应特征与关键临床相关联 人口统计信息。项目2：“肺癌细胞对SARS-COV-2感染和抗体的敏感性 介导的中和”确定肺癌和肺上皮细胞的个体间变异 支持SARS-COV-2病毒复制，抗体中和病毒感染的个体变化， 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有关。