Understanding Co-morbidities: COVID-19 in individuals living with HIV/AIDS

了解合并症：HIV/AIDS 患者中的 COVID-19

• 批准号: 10557898
• 负责人: Dhiraj Kumar Singh
• 金额: $ 98.98万
• 依托单位: TEXAS BIOMEDICAL RESEARCH INSTITUTE
• 依托单位国家: 美国
• 财政年份: 2022
• 资助国家: 美国
• 起止时间: 2022-02-01 至 2027-01-31
• 项目状态: 未结题
• 来源: https://reporter.nih.gov/project-details/10557898
• 关键词: 2019-nCoV; Ablation; Acceleration; Acquired Immunodeficiency Syndrome; Acute; Affect; Animals; Automobile Driving; CD4 Positive T Lymphocytes; COVID-19; COVID-19 impact; COVID-19 severity; COVID-19 susceptibility; COVID-19 therapeutics; Cell Compartmentation; Cells; Cessation of life; Chronic; Clinical; Clinical Management; Development; Disease; Exhibits; Foundations; Generations; Goals; HIV; HIV Infections; HIV/AIDS; Health; Immune; Immune response; Immunologic Deficiency Syndromes; Immunologic Factors; Immunologic Techniques; Immunologics; Immunotherapeutic agent; Individual; Infection; Intervention; Knowledge; Long COVID; Macaca; Macaca mulatta; Modeling; Monitor; Mutation; PET/CT scan; Pathogenesis; Pathogenicity; Pathology; Patient Care; Persons; Phase; Post-Acute Sequelae of SARS-CoV-2 Infection; Predisposition; Probability; Radiology Specialty; Reporting; Risk; Role; SARS-CoV-2 infection; SARS-CoV-2 variant; SIV; Therapeutic Intervention; Tissues; Validation; Variant; Viral; Virus; Virus Replication; cell type; co-infection; comorbidity; comparative; experience; immune activation; insight; nonhuman primate; pandemic disease; pathogen; prevent; reconstitution; severe COVID-19; vaccine development; vaccine hesitancy; 2019-nCoV; Ablation; Acceleration; Acquired Immunodeficiency Syndrome; Acute; Affect; Animals; Automobile Driving; CD4 Positive T Lymphocytes; COVID-19; COVID-19 impact; COVID-19 severity; COVID-19 susceptibility; COVID-19 therapeutics; Cell Compartmentation; Cells; Cessation of life; Chronic; Clinical; Clinical Management; Development; Disease; Exhibits; Foundations; Generations; Goals; HIV; HIV Infections; HIV/AIDS; Health; Immune; Immune response; Immunologic Deficiency Syndromes; Immunologic Factors; Immunologic Techniques; Immunologics; Immunotherapeutic agent; Individual; Infection; Intervention; Knowledge; Long COVID; Macaca; Macaca mulatta; Modeling; Monitor; Mutation; PET/CT scan; Pathogenesis; Pathogenicity; Pathology; Patient Care; Persons; Phase; Post-Acute Sequelae of SARS-CoV-2 Infection; Predisposition; Probability; Radiology Specialty; Reporting; Risk; Role; SARS-CoV-2 infection; SARS-CoV-2 variant; SIV; Therapeutic Intervention; Tissues; Validation; Variant; Viral; Virus; Virus Replication; cell type; co-infection; comorbidity; comparative; experience; immune activation; insight; nonhuman primate; pandemic disease; pathogen; prevent; reconstitution; severe COVID-19; vaccine development; vaccine hesitancy

Summary While COVID-19 continues to be a health challenge, very little is known about how COVID-19 affects people living with HIV (PLHIV). Based on the most recent reports originating from CDC and WHO, however, it appears that people with HIV may have a 30% greater likelihood of developing severe COVID-19 disease when infected with SARS-CoV-2. We will leverage the established rhesus macaque models of SARS-CoV-2 infection resulting in COVID-19 and SIV infection to characterize the effects of underlying SIV infection on the manifestation of both acute and post-acute COVID-19 sequelae. Our group was amongst few that established the rhesus macaque models of COVID-19 infection early on during the pandemic. Our model has been utilized to both study the immunological mechanisms of protection from SARS-CoV-2 infection, as well as for accelerated development of vaccine and therapeutics against COVID-19. Here we propose to couple this model with the long-standing, highly validated, pathogenic AIDS NHP model in SIV infected rhesus macaques to study a central hypothesis that underlying SIV infection and the resulting immunodeficiency/immune activation promotes the progression of a more severe COVID-19 presentation due to SARS-CoV-2 infection. As corollary, we hypothesize that ART does not completely suppress the ill effects of chronic immune activation due to SIV, it will not completely prevent the progression of severe COVID-19 due to SARS-CoV-2 infection in the macaque model. We have the experience in infecting rhesus macaques with SIV and treating these animals with ART to suppress viral replication and study immune mechanisms. By profiling the differences in dynamics of viral titers, induced tissue pathology, and underlying immunological perturbations, we will provide definitive knowledge in whether SIV infected rhesus macaques exhibit higher susceptibility to severe COVID-19. Furthermore, our studies will also be able to hint at the specific mechanisms which result in this susceptibility. Delineating these comorbid immunological factors driving susceptibility will enable better clinical monitoring and informed decisions for patient care. Mechanistic insights developed by this study is also imperative for the development of host-directed immunotherapeutic interventions for combating COVID-19 in PLHIV.

概括 虽然Covid-19仍然是一个健康挑战，但对于Covid-19如何影响人们，知之甚少 与艾滋病毒一起生活（PLHIV）。基于最新的报告，该报告来自CDC，但似乎 艾滋病毒患者在感染时可能患有严重的covid-19疾病的可能性增加30％。 与SARS-COV-2。我们将利用SARS-COV-2感染的已建立的恒河猕猴模型 在Covid-19和SIV感染中，表征了基本SIV感染对两者表现的影响 急性和急性后共证于199。我们的小组是建立恒河猕猴的少数小组 在大流行期间早期的Covid-19模型。我们的模型都被用于研究 免受SARS-COV-2感染保护的免疫学机制，以及加速发展 疫苗和治疗药物针对COVID-19。在这里，我们建议将该模型与长期的，高度的 经过验证的病原AIDS NHP模型在SIV感染了恒河猕猴中，研究了一个中心假设，即 潜在的SIV感染和产生的免疫缺陷/免疫激活促进了A的进展 由于SARS-COV-2感染引起的更严重的Covid-19呈现。作为推论，我们假设艺术确实 不能完全抑制由于SIV引起的慢性免疫激活的不良影响，它不会完全阻止 在猕猴模型中由于SARS-COV-2感染而导致的严重covid-19的进展。我们有经验 用SIV感染猕猴，并用艺术治疗这些动物以抑制病毒复制和 研究免疫机制。通过分析病毒滴度的动力学，诱导组织病理学和 潜在的免疫学扰动，我们将在SIV是否感染恒河神方面提供明确的知识 猕猴对严重的Covid-19表现出更高的敏感性。此外，我们的研究也可以暗示 导致这种敏感性的特定机制。描述这些合并症的免疫因素 驾驶易感性将使患者护理的更好的临床监测和知情决定。机理 这项研究开发的见解对于开发宿主指导的免疫治疗性也必须 在PLHIV中打击共vid-19的干预措施。