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

项目摘要 令人担忧的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 预防新冠肺炎疾病，引发了人们对潜在的新一波疫情的担忧。艾滋病病毒可能会使病情复杂化 新冠肺炎大流行的轨迹以及根除该病毒的努力。虽然大多数人都有 有能力的免疫系统在几天内成功清除SARS-CoV-2感染，艾滋病毒携带者 免疫力减弱可能会持续感染数月。免疫缺陷患者也可能 有较高的SARS-CoV-2再次感染风险，可进一步延长传染性持续时间 病毒载量。因此，慢性感染者有可能在较长时间内具有传染性。 并可能维持在社区中的传播。与其他病毒类似，SARS-CoV-2会积累突变 随着时间的推移，它会在主机内复制。因此，慢性SARS-CoV-2感染在 减弱的免疫系统可能为病毒复制和复制提供所需的时间和环境 进化与生存优势相关的基因突变，包括增加传播性和 对新冠肺炎疫苗或治疗产生耐药性。这项拟议的研究旨在了解总体影响 高HIV环境下HIV感染对SARS-CoV-2病毒进化和传播动态的影响 流行率。我们将通过整合患者层面的SARS-CoV-2基因组数据来解决当前的知识差距 临床数据和流行病学数据达到以下目的：1)我们将确定艾滋病病毒的影响 感染新冠肺炎传播动态和出现SARS-CoV-2变异株；以及2)我们将 确定HIV相关免疫抑制对SARS-CoV-2变异获得的影响。为 第一个目标是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。 和SARS-CoV-2在人口规模上的病毒演变，以及描述驱动 个人和人群层面的新冠肺炎传播。对于第二个目标，我们将招募和跟随一个队列 新冠肺炎对合并和不合并艾滋病毒感染患者的疗效判断 免疫抑制对SARS-CoV-2新变异率的影响。拟议的研究还将利用 主动病例查找，以最大限度地减少抽样偏差。该项目的调查结果将为开发最佳 公共卫生干预措施，通过扰乱传播链来控制大流行，防止 令人震惊的变种的出现和传播。

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.