Admin-Core-001

管理核心-001

• 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
• 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

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.

摘要 本申请是根据CA-21 - 033特别关注通知提交的。SARS- 冠状病毒-2（SARS-CoV-2）已经在世界范围内迅速传播，引起全球大流行。有许多 与COVID-19和癌症患者相关的合并症和风险因素的风险可能更高， 他们往往年龄较大，可能有多种合并症，并且经常受到免疫抑制。癌症患者， 特别是那些艾滋病毒阳性的人，在艾滋病毒仍然流行的撒哈拉以南非洲， 更高的疾病风险，因为他们可能没有完全免疫重建。我们的团队有一个长期的 与我们的赞比亚伙伴合作，研究癌症发病机制与艾滋病毒。与 随着赞比亚SARS-CoV-2感染人数的增加，确定SARS-CoV-2的影响很重要 感染和COVID-19的癌症患者或无艾滋病毒。我们的总体目标是发展一个更好的 了解艾滋病毒的潜在协同效应，以及癌症患者先前暴露于其他传染病 在撒哈拉以南非洲的COVID-19疾病发展中的患者。我们的数据显示， 撒哈拉以南非洲地区的人口在2010年之前曾接触过一些人类冠状病毒， 大流行，并可能赋予一些针对SARS-CoV-2感染的交叉保护性免疫应答， 随后的COVID-19，如果感染。此外，我们现在有初步数据显示， 2019冠状病毒病伴和不伴癌症患者对不同感染的体液免疫应答 和艾滋病毒，这将为我们提供一个途径，以进一步研究其他传染病的作用， 2019冠状病毒病。我们的第二个目标是预测基于腺病毒载体的SARS-CoV-2的疗效 通过我们对所有潜在的体液免疫应答的高通量分析， 感染.我们假设，先前暴露于其他传染病的COVID-19患者，包括 季节性冠状病毒将有一个更温和的COVID-19疾病过程，但癌症和艾滋病毒感染， COVID-19患者将导致控制SARS-CoV-2的有效免疫应答降低，并影响其 疾病历程我们的具体目标是：1）确定COVID-19与艾滋病毒之间的关系， 其他传染病和癌症。2)COVID-19病例的纵向随访及其控制 恢复，以确定其病毒学参数、抗SARS-CoV-2体液应答的变化，以及 炎症状态。拟议的研究是重要和及时的，因为它将与我们正在进行的研究产生协同作用。 艾滋病毒相关恶性肿瘤U54项目（ZAMDAPP）。产生的结果将有助于确定 在高风险人群中，既往暴露于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，也可以预测基于COVID-19的腺病毒载体的疗效 疫苗在该地区。我们的研究结果将有助于预测COVID-19病程的程度并预防疾病 艾滋病毒感染的癌症患者在赞比亚和其他地区的进展。