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 本申请书是针对被确认为CA-21-033的特别利益通知而提交的。非典-- 冠状病毒-2(SARS-CoV-2)在全球范围内迅速传播，引发了全球大流行。有一个号码 与新冠肺炎相关的并发症和风险因素与癌症患者可能面临更高的风险，因为 他们往往年龄较大，可能有多种合并症，而且往往免疫抑制。癌症患者， 特别是那些艾滋病毒+的人，在艾滋病毒仍在流行的撒哈拉以南非洲(SSA)，尤其是 疾病风险更高，因为它们可能不是完全免疫的重组。我们团队有一个长期的 与我们的赞比亚合作伙伴合作，研究癌症与艾滋病毒的致病机制。与 赞比亚SARS-CoV-2感染人数不断增加，确定SARS-CoV-2的影响至关重要 艾滋病病毒携带者与癌症患者新冠肺炎感染关系的研究我们的总目标是发展一个更好的 了解艾滋病毒的潜在协同效应，以及癌症中先前接触其他传染病的情况 新冠肺炎患者在撒哈拉以南非洲的疾病发展。这是由我们的数据表明的 撒哈拉以南非洲地区的人口在流感爆发前接触过多种人类冠状病毒 可能会对SARS-CoV-2感染产生一些交叉保护性免疫反应，并 随后的新冠肺炎，如果感染了。此外，我们现在有初步数据显示， 新冠肺炎癌与非癌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，进一步调查其他传染病在 新冠肺炎。我们的次要目标是预测腺病毒载体载体的SARS-CoV-2的疗效 疫苗通过我们的高通量分析针对所有潜在的体液免疫反应 感染。我们假设新冠肺炎患者以前接触过其他传染病，包括 季节性冠状病毒会有一个更温和的新冠肺炎病程，但癌症和艾滋病毒感染 新冠肺炎患者在控制SARS-CoV-2时会导致免疫应答效果降低，影响患者的健康 疾病疗程。我们的具体目标是：1)确定新冠肺炎与艾滋病毒和 其他传染病和癌症。2)新冠肺炎病例纵向随访及对照研究 恢复以确定其病毒学参数的变化，抗SARS-CoV-2体液反应，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 关于艾滋病毒相关恶性肿瘤的U54项目(ZAMDAPP)。生成的结果将有助于确定 既往接触其他传染病是否会在高危人群中不同程度影响新冠肺炎病程 HIV阳性的癌症患者在SSA中的表达，也可以预测腺病毒载体载体新冠肺炎的疗效 该地区的疫苗。我们的研究结果将有助于预测新冠肺炎的病程范围和预防疾病 赞比亚及其他地区感染艾滋病毒的癌症患者的进展情况。