Characterization of Persistent COVID-19

项目总结 免疫抑制的个人越来越被认为是新冠肺炎疫情的焦点。他们是 慢性新冠肺炎感染、治疗失败、严重疾病和新冠肺炎风险增加 死亡率。也有证据表明，它们也可能是新冠肺炎变异体/亚变种出现的驱动因素。 由于它们有长期感染和加速病毒进化的风险。然而，免疫和病毒 在这一人群中发生慢性感染、病毒进化和耐药性的机制很差。 明白了。改善这一高危人群的健康状况，降低病毒进化的风险 对于耐药性，迫切需要解决我们对哪些免疫缺陷的理解上的差距 增加慢性新冠肺炎感染的风险，加速病毒进化。这项提案的主要目标是 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。这个 建议调查人员将建立一个现有的翻译研究基础设施，具有招募队列的经验 有新冠肺炎的免疫抑制患者，在临床研究、病毒定量、 病毒培养、测序和免疫学。研究结果将提供有关新冠肺炎的关键新数据 免疫抑制的发病机制、变异演变、治疗反应及临床护理 人口。通过加深我们对清除病毒的免疫途径的理解，这一结果 该提案还可能确定下一代疫苗和疗法的潜在目标。

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.