Characterization of Persistent COVID-19

持续性 COVID-19 的特征

基本信息

批准号：
10744322
负责人：
Amy K Barczak
金额：
$ 86.87万
依托单位：
BRIGHAM AND WOMEN'S HOSPITAL
依托单位国家：
美国
项目类别：
财政年份：
2023
资助国家：
美国
起止时间：
2023-08-10 至 2027-07-31
项目状态：
未结题

来源：
https://reporter.nih.gov/project-details/10744322
关键词：
2019-nCoV Acceleration Address Amino Acids Antibody titer measurement Antigens Antiviral Agents Area B cell therapy CD8-Positive T-Lymphocytes COVID-19 COVID-19 mortality COVID-19 pandemic COVID-19 pathogenesis COVID-19 therapeutics Characteristics Chronic Clinical Research Collaborations Data Disease Drug resistance Enrollment Epidemiology Evolution General Population Genes Genetic Goals Health Hematologic Neoplasms Hematopoietic Stem Cell Transplantation Immune Immune response Immunocompetent Immunocompromised Host Immunologic Deficiency Syndromes Immunologics Immunology Immunosuppression Incidence Individual Infection Laboratories Long COVID Methods Monoclonal Antibodies Nature Outcome Participant Pathway interactions Patients Persons Play Population Productivity Public Health Publications RNA Regimen Research Infrastructure Research Personnel Resistance Risk Risk Factors Risk Reduction Role SARS-CoV-2 infection SARS-CoV-2 variant Sampling Severity of illness Source Symptoms T cell response Therapeutic Translational Research Treatment Failure Variant Viral Viral Drug Resistance Viral Load result Virus Virus Diseases antiviral drug development chronic infection clinical care clinical risk cohort deep sequencing experience high risk population immunosuppressed improved novel vaccines recruit response transcriptome sequencing transmission process treatment response viral RNA virology

项目摘要

PROJECT SUMMARY Immunosuppressed individuals are increasingly recognized as a focal point of the COVID-19 epidemic. They are at increased risk of chronic COVID-19 infection, therapeutic treatment failure, severe disease and COVID-19 mortality. Evidence is also emerging that they may also be drivers of COVID-19 variant/subvariant emergence, due to their risk of prolonged infection and accelerated viral evolution. However, the immune and viral mechanisms by which chronic infection, viral evolution, and drug resistance occur in this population are poorly understood. To improve health outcomes for this high-risk population and to reduce the risk of viral evolution and drug resistance, there is an urgent need to address gaps in our understanding of which immune deficiencies increase the risk of chronic COVID-19 infection and accelerated viral evolution. The primary goal of this proposal is to determine the host and virologic characteristics that promote chronic viral infection and viral evolution. The proposing investigators will an existing translational research infrastructure with experience recruiting cohorts of immunosuppressed individuals with COVID-19 and broad expertise in clinical research, viral quantification, viral culture, sequencing, and immunology. The results will provide critical new data about COVID-19 pathogenesis, variant evolution, therapeutic response, and inform the clinical care of immunosuppressed populations. By deepening our understanding of the immune pathways of viral clearance, the results from this proposal may also identify potential targets for the next generation of vaccines and therapeutics.

项目概要免疫抑制个体越来越被认为是 COVID-19 流行病的焦点。他们是慢性 COVID-19 感染、治疗失败、严重疾病和 COVID-19 的风险增加死亡。越来越多的证据表明它们也可能是 COVID-19 变体/亚变体出现的驱动因素，由于它们存在长期感染和加速病毒进化的风险。然而，免疫和病毒该人群中慢性感染、病毒进化和耐药性发生的机制尚不清楚明白了。改善这一高危人群的健康状况并降低病毒进化和传播的风险耐药性，迫切需要解决我们对哪些免疫缺陷的理解上的差距增加慢性 COVID-19 感染的风险并加速病毒进化。本提案的主要目标是确定促进慢性病毒感染和病毒进化的宿主和病毒学特征。这提议研究人员将拥有具有招募队列经验的现有转化研究基础设施患有 COVID-19 的免疫抑制个体以及在临床研究、病毒定量、病毒培养、测序和免疫学。结果将提供有关 COVID-19 的重要新数据发病机制、变异进化、治疗反应，并为免疫抑制患者的临床护理提供信息人口。通过加深我们对病毒清除的免疫途径的理解，这一结果该提案还可能确定下一代疫苗和治疗方法的潜在目标。