Admin-Core-001

管理核心-001

基本信息

批准号：
10496102
负责人：
Chipepo Kankasa
金额：
$ 18.79万
依托单位：
UNIVERSITY OF NEBRASKA LINCOLN
依托单位国家：
美国
项目类别：
财政年份：
2017
资助国家：
美国
起止时间：
2017-09-15 至 2022-08-31
项目状态：
已结题

来源：
https://reporter.nih.gov/project-details/10496102
关键词：
2019-nCoV AIDS related cancer Acquired Immunodeficiency Syndrome Adenovirus Vector Adenoviruses Affect Africa Africa South of the Sahara African Antibodies Antibody Repertoire Biological Assay COVID-19 COVID-19 patient COVID-19 prevention COVID-19 vaccine Cancer Patient Cardiovascular Diseases Case Study China Clinical Collaborations Communicable Diseases Coronavirus Country Data Development Diabetes Mellitus Diagnosis Disease Disease Progression Elderly Enrollment Epidemic Equipment Exposure to HIV HIV Infections HIV Seropositivity HIV-1 High Prevalence Hospitals Human Human Herpesvirus 8 Human Resources Human papilloma virus infection Hypertension Immune Immune response Immune system Immunofluorescence Immunologic Individual Infection Infectious Agent Inflammation Kaposi Sarcoma Knowledge Leukocytes Lung diseases Malignant Neoplasms Measures Outcome Participant Pathogenesis Plasma Population Recovery Reporting Resources Risk Factors Role SARS-CoV-2 antibody SARS-CoV-2 infection Sampling Squamous Cell Neoplasms Symptoms Teaching Hospitals Techniques Technology Time Universities Virus Zambia base bed capacity case control comorbidity cytokine disorder risk follow-up high risk high throughput analysis human coronavirus immunosuppressed interest mortality nasopharyngeal swab next generation novel ocular surface ocular surface squamous neoplasia pandemic disease potential biomarker prevent programs reconstitution recruit response severe COVID-19 virology

项目摘要

Abstract This application is submitted in response to the notice of special interest identified as CA-21-033. The SARS- coronavirus-2 (SARS-CoV-2) has rapidly spread worldwide causing the global pandemic. There are a number of comorbidities and risk factors associated with COVID-19 and cancer patients could be at higher risk since they tend to be older, likely to have multiple comorbidities, and are often immunosuppressed. Cancer patients, especially those who are HIV+, in sub-Saharan Africa (SSA) where HIV is still epidemic are at particularly higher risk of disease since they may not be completely immune reconstituted. Our team has a long-term collaboration with our Zambia partners to study cancer pathogenesis in conjunction with HIV. With the increasing number of SARS-CoV-2 infection in Zambia, it is important to determine the effects of SARS-CoV-2 infection and COVID-19 in cancer patients with or without HIV. Our overall objective is to develop a better understanding of potential synergistic effects of HIV, and prior exposure to other infectious diseases in cancers patients on COVID-19 disease development in sub-Saharan Africa. This was suggested by our data showing that the sub-Saharan Africa populations have exposures to a number of human coronaviruses prior to the pandemic and may confer some cross-protective immune response against SARS-CoV-2 infection and subsequent COVID-19, if infected. In addition, we now have preliminary data showing that there are differential humoral immune responses against different infections between COVID-19 patients with and without cancers and HIV, which will provide an avenue for us to further investigate the role of other infectious diseases in COVID-19. Our secondary objective is to predict the efficacy of adenovirus-vector based SARS-CoV-2 vaccines through our high throughput analysis of the humoral immune responses against all potential infections. We hypothesize that COVID-19 patients with prior exposure to other infectious diseases including seasonal coronaviruses will have a more tempered COVID-19 disease course, but cancer and HIV infection in COVID-19 patients will lead to less effective immune responses in controlling SARS-CoV-2 and affect their disease courses. Our specific aims are: 1) To determine the relationships between COVID-19 with HIV and other infectious diseases and cancer. 2) Longitudinal follow up of COVID-19 cases and controls on their recovery to determine changes in their virological parameters, anti-SARS-CoV-2 humoral response, and inflammation status. The proposed study is significant and timely because it will synergize with our ongoing U54 project (ZAMDAPP) on HIV-associated malignancies. The results generated will help to determine whether prior exposure to other infectious disease can affect the COVID-19 course differently in the high risk HIV positive cancer patients in SSA, and may also predict the efficacy of adenovirus-vector based COVID-19 vaccines in the region. Our results will help predict the extent of COVID-19 course and prevent disease progression in the HIV infected cancer patients in Zambia and beyond.

抽象的本申请是为了响应编号为 CA-21-033 的特殊利益通知而提交的。非典—— 冠状病毒-2 (SARS-CoV-2) 已在全球范围内迅速传播，导致全球大流行。有一些与 COVID-19 和癌症患者相关的合并症和危险因素可能面临更高的风险，因为他们往往年龄较大，可能患有多种合并症，并且通常免疫抑制。癌症患者，尤其是那些艾滋病病毒感染者，在艾滋病毒仍然流行的撒哈拉以南非洲 (SSA) 患病的风险更高，因为它们可能没有完全免疫重建。我们的团队有长期的与我们的赞比亚合作伙伴合作，研究与艾滋病毒相关的癌症发病机制。随着赞比亚 SARS-COV-2 感染人数不断增加，确定 SARS-COV-2 的影响非常重要感染或未感染 HIV 的癌症患者的感染和 COVID-19。我们的总体目标是开发更好的了解艾滋病毒和先前接触过其他传染病对癌症的潜在协同作用撒哈拉以南非洲地区 COVID-19 疾病发展的患者。我们的数据表明了这一点撒哈拉以南非洲地区的人口在此次疫情之前就已接触过多种人类冠状病毒大流行并可能针对 SARS-CoV-2 感染产生一些交叉保护性免疫反应，如果感染了随后的 COVID-19。此外，我们现在有初步数据表明，存在差异患有癌症和未患有癌症的 COVID-19 患者针对不同感染的体液免疫反应和艾滋病毒，这将为我们进一步研究其他传染病在新冠肺炎。我们的次要目标是预测基于腺病毒载体的 SARS-CoV-2 的功效通过我们对所有潜在的体液免疫反应的高通量分析来生产疫苗感染。我们假设 COVID-19 患者之前曾接触过其他传染病，包括季节性冠状病毒的 COVID-19 病程会更加温和，但癌症和 HIV 感染 COVID-19 患者将导致控制 SARS-CoV-2 的免疫反应效果较差，并影响他们的免疫反应。疾病课程。我们的具体目标是： 1) 确定 COVID-19 与 HIV 之间的关系其他传染病和癌症。 2) 对 COVID-19 病例进行纵向随访并对其进行控制恢复以确定其病毒学参数、抗 SARS-CoV-2 体液反应的变化，以及炎症状态。拟议的研究意义重大且及时，因为它将与我们正在进行的研究产生协同作用关于 HIV 相关恶性肿瘤的 U54 项目 (ZAMDAPP)。生成的结果将有助于确定在高风险人群中，之前接触过其他传染病是否会对 COVID-19 病程产生不同的影响 SSA 中的 HIV 阳性癌症患者，还可以预测基于腺病毒载体的 COVID-19 的疗效该地区的疫苗。我们的结果将有助于预测 COVID-19 病程的程度并预防疾病赞比亚及其他地区艾滋病毒感染癌症患者的进展。