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.

项目摘要 SARS-COV-2变体的出现和传播是威胁全球健康和我们的能力 预防199疾病，引起人们对潜在的大流行新潮的担忧。艾滋病毒可能会复杂 COVID-19大流行的轨迹和消除病毒的努力。虽然大多数人 有能力的免疫系统在几天之内成功清除SARS-COV-2感染，与艾滋病毒感染 免疫力减弱会持续数月持续感染。免疫缺陷的人也可能 SARS-COV-2重新感染的风险更高，可以进一步扩大传染性持续时间 病毒负荷。结果，长期感染的个体可能会长时间传染 并可以维持社区的传播。与其他病毒类似，SARS-COV-2累积突变 随着时间的流逝，它在主机中复制。因此，慢性SARS-COV-2感染在 弱化的免疫系统可能会提供病毒复制所需的时间和环境 进化与生存优势相关的基因突变，包括增加的可传播性和 对Covid-19疫苗或治疗的抗性。拟议的研究旨在了解总体影响 HIV高的环境中SARS-COV-2病毒演化和传播动力学上的HIV感染 流行率。我们将通过整合SARS-COV-2基因组数据，患者级来解决当前的知识差距 临床数据和流行病学数据以实现以下目的：1）我们将确定HIV的影响 关于Covid-19的传播动力学的感染和SARS-COV-2变体的出现； 2）我们将 确定与HIV相关的免疫抑制对获得SARS-COV-2突变的影响。为了 第一个目的，将采用高级系统动力学方法来确定HIV如何影响传播 SARS-COV-2在人群量表上的病毒演变，以及描述驱动的风险因素 个人和人口级别的共同传播。为了第二个目标，我们将招募并跟随队列 与HIV感染有或没有HIV感染的19例Covid-19 对新兴SARS-COV-2突变速率的免疫抑制。拟议的研究也将利用 活跃的病例发现以最大程度地减少采样偏差。该项目的发现将为最佳发展提供信息 公共卫生干预措施通过破坏传播链并防止 令人震惊的变体的出现和传播。