The effect of HIV on SARS-CoV-2 transmission and emergence of variants of concern

HIV 对 SARS-CoV-2 传播的影响以及令人关注的变种的出现

• 批准号: 10659257
• 负责人: Chawangwa Modongo
• 金额: $ 55.97万
• 依托单位: UNIVERSITY OF CALIFORNIA-IRVINE
• 依托单位国家: 美国
• 财政年份: 2022
• 资助国家: 美国
• 起止时间: 2022-07-05 至 2026-06-30
• 项目状态: 未结题
• 来源: https://reporter.nih.gov/project-details/10659257
• 关键词: 2019-nCoV; Affect; Area; Botswana; CD4 Positive T Lymphocytes; COVID-19; COVID-19 impact; COVID-19 pandemic; COVID-19 patient; COVID-19 prevention; COVID-19 severity; COVID-19 treatment; COVID-19 vaccine; Case Study; Cell Count; Cells; Chronic; Clinical; Clinical Data; Cohort Studies; Communities; Country; DNA Sequence Alteration; Data; Development; Disease; Environment; Epidemic; Epidemiology; Event; Evolution; Foundations; Functional disorder; Future; Genetic Recombination; Goals; HIV; HIV Infections; Health; High Prevalence; Household; Immune; Immune system; Immunity; Immunocompetent; Immunocompromised Host; Immunologic Deficiency Syndromes; Immunosuppression; Incidence; Individual; Infection; Intervention; Knowledge; Methods; Molecular; Monitor; Mutation; National Institute of Allergy and Infectious Disease; Patients; Pattern; Persons; Play; Population; Prevalence; Public Health; RNA; Research; Resistance; Risk Factors; Role; SARS-CoV-2 B.1.1.529; SARS-CoV-2 B.1.617.2; SARS-CoV-2 genome; SARS-CoV-2 infection; SARS-CoV-2 transmission; SARS-CoV-2 variant; Sampling; Sampling Biases; Subgroup; System; Time; Tuberculosis; Vaccination; Variant; Viral; Viral Load result; Virus; case finding; chronic infection; co-infection; cohort; comorbidity; epidemiologic data; epidemiology study; experience; future pandemic; genome sequencing; genomic data; genomic epidemiology; global health; high risk; improved; insight; interest; pandemic disease; pandemic response; population based; pressure; prevent; programs; public health intervention; recruit; transmission process; variants of concern; whole genome

Project Summary The emergence and spread of SARS-CoV-2 variants of concern is threatening global health and our ability to prevent COVID-19 disease, raising concerns about a potential new wave of the pandemic. HIV may complicate the trajectory of the COVID-19 pandemic and efforts to eradicate the virus. While most people with a competent immune system successfully clear SARS-CoV-2 infection within days, people living with HIV with weakened immunity can carry persistent infection for months. Individuals with immunodeficiency may also have a higher risk of SARS-CoV-2 reinfection that can further extend the duration of infectiousness with high viral load. As a result, chronically infected individuals are potentially contagious for an extended period of time and may sustain transmission in the community. Similar to other viruses, SARS-CoV-2 accumulates mutations over time as it replicates within the host. Therefore, chronic SARS-CoV-2 infection in the context of a weakened immune system may provide the time and the environment needed for the virus to replicate and evolve genetic mutations associated with survival advantages, including increased transmissibility and resistance to COVID-19 vaccines or treatment. The proposed research aims to understand the overall impact of HIV infection on the SARS-CoV-2 viral evolution and transmission dynamics in a setting with high HIV prevalence. We will address current knowledge gaps by integrating SARS-CoV-2 genomic data, patient-level clinical data, and epidemiological data to achieve the following aims: 1) we will determine the effect of HIV infection on the transmission dynamics of COVID-19 and emergence of SARS-CoV-2 variants; and 2) we will determine the effect of HIV-associated immunosuppression on the acquisition of SARS-CoV-2 mutations. For the first Aim, advanced phylodynamic methods will be applied to determine how HIV affects the transmission and viral evolution of SARS-CoV-2 on a population scale, as well as to describe risk factors that drive individual and population-level COVID-19 transmission. For the second Aim, we will recruit and follow a cohort of COVID-19 patients with and without HIV infection to determine the effect of HIV-associated immunosuppression on the rate of emerging SARS-CoV-2 mutations. The proposed research will also utilize active case finding to minimize sampling bias. Findings from this project will inform the development of optimal public health interventions to control the pandemic by disrupting transmission chains and prevent the emergence and spread of alarming variants.

项目概要 值得关注的 SARS-CoV-2 变种的出现和传播正在威胁全球健康和我们的能力 预防 COVID-19 疾病，引发人们对潜在新一波大流行的担忧。艾滋病毒可能会使情况复杂化 COVID-19 大流行的轨迹以及根除该病毒的努力。虽然大多数人都有 强大的免疫系统在几天内成功清除 SARS-CoV-2 感染，艾滋病毒感染者 免疫力下降可能会持续感染数月。 Individuals with immunodeficiency may also SARS-CoV-2 再次感染的风险较高，这可能会进一步延长高传染性的持续时间 病毒载量。因此，慢性感染者在较长一段时间内具有潜在的传染性 并可能维持社区传播。与其他病毒类似，SARS-CoV-2 会积累突变 随着时间的推移，它会在宿主内复制。因此，慢性 SARS-CoV-2 感染在 免疫系统减弱可能为病毒复制和传播提供所需的时间和环境。 进化出与生存优势相关的基因突变，包括增加的传染性和 对 COVID-19 疫苗或治疗产生耐药性。拟议的研究旨在了解总体影响 HIV 感染对 SARS-CoV-2 病毒进化和高 HIV 环境中传播动态的影响 流行率。我们将通过整合 SARS-CoV-2 基因组数据、患者层面的数据来解决当前的知识差距 临床数据和流行病学数据以达到以下目的：1）我们将确定HIV的效果 感染对 COVID-19 传播动态和 SARS-CoV-2 变种出现的影响； 2）我们将 确定 HIV 相关免疫抑制对 SARS-CoV-2 突变获得的影响。为了 第一个目标，将应用先进的系统动力学方法来确定艾滋病毒如何影响传播 SARS-CoV-2 在人群规模上的病毒进化，以及描述驱动的风险因素 个人和人群层面的 COVID-19 传播。对于第二个目标，我们将招募并跟踪一批人 对感染和未感染 HIV 的 COVID-19 患者进行研究，以确定 HIV 相关的影响 免疫抑制对新出现的 SARS-CoV-2 突变率的影响。拟议的研究还将利用 积极寻找案例以尽量减少抽样偏差。该项目的研究结果将为最佳的开发提供信息 公共卫生干预措施，通过破坏传播链和预防疫情来控制大流行 令人震惊的变种的出现和传播。