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 血清学卓越中心的总体研究主题“脆弱性” 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 导致肺癌患者极易遭受 SARS 发病和死亡影响的因素之间的差异 通过抗体反应的血清学分析和个体间变异研究来确定 CoV-2 感染 患者来源的肺肿瘤和上皮细胞对 SARS-CoV-2 感染的影响。我们将表征并比较肺 癌症患者对 SARS-COV-2 感染或 SARS-COV-2 疫苗的抗体反应 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；并定量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策略 肺癌患者对抗 COVID-19 的发展。虽然由感染或疫苗诱导的抗体 对许多病毒具有保护作用，但尚未确定 SARS-CoV-2 抗体是否具有保护作用，如何保护 需要多少抗体、什么类型的抗体来提供保护，以及保护能持续多久尚不清楚。 同样，我们不知道肺癌患者是否能够产生有效的免疫反应，以及不同方面是否能够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 与未感染的人相比，患者对 SARS-CoV-2 感染的抗体反应不同（例如较弱） 肺癌，以及它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， 这些共同可以解释肺癌患者的侵袭性病程和高死亡率 与新冠肺炎 (COVID-19) 相关。我们的 U54 将确定是自然感染还是 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 人）；并确定是否存在差异 抗体反应与年龄、性别、烟草史和种族/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：“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，肺癌患者的抗体反应及其纵向功能 自然感染和疫苗接种后，并将血清学反应特征与关键临床联系起来， 人口统计信息。项目2：“肺癌细胞对SARS-CoV-2感染的易感性及抗体- 介导的中和作用”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个体间变异，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。