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: 10548494
• 负责人: Chawangwa Modongo
• 金额: $ 59.62万
• 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/10548494
• 关键词: 2019-nCoV; Address; 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 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; base; case finding; chronic infection; co-infection; cohort; comorbidity; epidemiologic data; epidemiology study; experience; genome sequencing; genomic data; genomic epidemiology; global health; high risk; improved; insight; interest; pandemic disease; 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COVID-19疾病，引发了对潜在新一波大流行的担忧。艾滋病毒可能使 COVID-19大流行的轨迹以及根除病毒的努力。虽然大多数人有一个 有能力的免疫系统在几天内成功清除SARS-CoV-2感染， 免疫力减弱会导致数月的持续感染。免疫缺陷患者也可能 具有较高的SARS-CoV-2再感染风险，这可以进一步延长高感染性的持续时间。 病毒载量因此，慢性感染者在很长一段时间内具有潜在的传染性 并可能在社区中持续传播。与其他病毒类似，SARS-CoV-2积累突变 随着时间的推移，它在主机内复制。因此，慢性SARS-CoV-2感染的背景下， 减弱的免疫系统可以提供病毒复制所需的时间和环境， 进化出与生存优势相关的基因突变，包括增加遗传性， 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病毒进化和在HIV高感染环境中传播动力学的影响 普遍性。我们将通过整合SARS-CoV-2基因组数据、患者水平 临床数据和流行病学数据，以达到以下目的：1）我们将确定艾滋病毒的效果 感染对COVID-19传播动力学的影响以及SARS-CoV-2变种的出现;以及2）我们将 确定HIV相关免疫抑制对获得SARS-CoV-2突变的影响。为 在第一个目标中，将采用先进的生物动力学方法来确定艾滋病毒如何影响传播 以及SARS-CoV-2在人群规模上的病毒进化，以及描述驱动SARS-CoV-2的风险因素。 个人和人群水平的COVID-19传播。对于第二个目标，我们将招募并跟踪一个队列 有和没有艾滋病毒感染的COVID-19患者，以确定艾滋病毒相关的 免疫抑制对SARS-CoV-2突变率的影响。该研究还将利用 积极寻找病例，以尽量减少抽样偏差。该项目的研究结果将为开发最佳 公共卫生干预措施，通过阻断传播链控制大流行， 令人震惊的变种的出现和传播。