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.

抽象的 该申请是根据CA-21-033的特殊利益通知提交的。 SARS- 冠状病毒2（SARS-COV-2）在全球范围内迅速传播，引起全球大流行。有一个数字 与Covid-19和癌症患者有关的合并症和危险因素的风险可能更高，因为 它们倾向于年龄较大，可能具有多种合并症，并且经常被免疫抑制。癌症患者， 尤其是那些在撒哈拉以南非洲（SSA）的艾滋病毒+的人，艾滋病毒仍然流行的人尤其是 疾病的风险更高，因为它们可能无法完全免疫重构。我们的团队长期 与赞比亚合作伙伴合作研究癌症发病机理与HIV结合。与 赞比亚的SARS-COV-2感染数量增加，确定SARS-COV-2的影响很重要 患有或患有HIV的癌症患者的感染和COVID-19。我们的总体目标是发展更好 了解艾滋病毒的潜在协同作用，并事先暴露于癌症中的其他传染病 撒哈拉以南非洲疾病发展的患者。这是我们的数据显示的 撒哈拉以南非洲人口在此之前有许多人类冠状病毒的暴露 大流行，可能赋予SARS-COV-2感染的一些交叉保护免疫反应和 随后的Covid-19，如果感染。此外，我们现在有初步数据表明存在差异 与癌症患者和没有癌症患者之间的不同感染的体液免疫反应 和艾滋病毒，这将为我们提供进一步调查其他传染病的作用的途径 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 通过我们对所有潜力的体液免疫反应的高吞吐量分析疫苗 感染。我们假设Covid-199患者先前暴露于其他传染病，包括 季节性冠状病毒将有更调整的Covid-19疾病病程，但癌症和HIV感染 COVID-19患者将导致控制SARS-COV-2的有效免疫反应较低，并影响其 疾病课程。我们的具体目的是：1）确定Covid-19与HIV和 其他传染病和癌症。 2）COVID-19案件的纵向随访及其对照 恢复以确定其病毒学参数的变化，抗SARS-COV-2体液反应和 炎症状态。拟议的研究很重要，及时，因为它将与我们正在进行的 U54项目（Zamdapp）关于HIV相关的恶性肿瘤。产生的结果将有助于确定 在高风险方面，事先接触其他传染病是否会影响共同疾病的过程有所不同 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的功效 该地区的疫苗。我们的结果将有助于预测Covid-19课程的程度并预防疾病 赞比亚及其他地区的HIV感染癌症患者的进展。