Administrative Supplements for Coronavirus Disease 2019 (COVID-19) Research

2019 年冠状病毒病 (COVID-19) 研究行政补充

• 批准号: 10177193
• 负责人: Cuong Q Nguyen
• 金额: $ 22.5万
• 依托单位: UNIVERSITY OF FLORIDA
• 依托单位国家: 美国
• 财政年份: 2020
• 资助国家: 美国
• 起止时间: 2020-07-23 至 2021-03-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/10177193
• 关键词: 2019-nCoV; Administrative Supplement; Adult; Aerosols; Affinity; Age; Alleles; Antigen Presentation; Antigens; Binding; Biological Assay; Biological Markers; Breathing; COVID-19; Cell physiology; Cessation of life; Child; Chills; China; Clinical; Congestive; Coronavirus; Coughing; Country; Data; Databases; Dengue; Disease; Epitopes; Fatigue; Fever; Foundations; Gene Frequency; General Population; Genetic; Genetic Predisposition to Disease; Genomic DNA; Genotype; HIV-1; HLA Antigens; Health Personnel; Human; Human Genetics; Immune; Immune response; Individual; Intervention; Laboratories; Measures; Medical; Membrane; Middle East Respiratory Syndrome; Mutation; Nucleocapsid; Oral health; Oxygen; Patients; Peptides; Peripheral Blood Mononuclear Cell; Persons; Play; Population; Predisposition; Production; Province; Reporting; Research; Risk; Role; SARS coronavirus; Safety; Saliva; Sampling; Science; Severe Acute Respiratory Syndrome; Severities; Severity of illness; Shortness of Breath; Sore Throat; Source; Surface; Symptoms; System; T cell response; T-Lymphocyte; Testing; Time; Travel; Vaccines; Ventilator; Viral; Viral Antibodies; Viral Antigens; Virus; Zoonoses; aged; antigen binding; base; cytokine; genetic association; high risk; hospitalization rates; human leukocyte antigen testing; human old age (65+); in silico; infection rate; novel coronavirus; pandemic disease; prevent; receptor; response; seroconversion; transmission process; viral detection; viral transmission; whole genome

COVID-19 is caused by a suspected zoonotic source of Severe Acute Respiratory Syndrome-Coronavirus-2 (SARS-CoV-2). While coronaviruses (CoVs) are relatively common, mutations can cause severe symptoms in humans; the challenges of SARS-CoV-2 are: the long incubation period (2-14 days, median 5.1 days), high viral titer which can appear while a COVID-19+ patient is asymptomatic, and the long period of time in which it is viable outside of its host, both airborne and on surfaces. It is estimated as of May 28, 2020, that there are over 5.7 million cases in 212 countries. Symptoms can range from mild to severe and may include: fever, coughing, shortness of breath, sore throat, fatigue, congestion, and chills. Of those cases, 13.8% require medical interventions, with 6% of patients dying Tragically, there are no available vaccines against SARS-CoV-2. With a wide range of clinical symptoms and more importantly a large population of asymptomatic COVID-19+ patients, a crucial question regarding genetic susceptibility, i.e. whether human leukocyte antigens (HLA) play a role in the patient symptomology. Preliminary in-silico data have revealed binding affinity of specific HLAs to SARSCoV-2 antigens, indicating a genetic HLA association with COVID-19 clinical symptoms, which is the primary objective of this application. We hypothesize that “A certain HLA allele or combination of certain alleles can serve as biomarker for the severity of COVID-19”. To test this hypothesis, we propose to define HLA binding epitopes from dominant SARS-CoV-2 T cell antigens using in-silico analysis (Aim 1), determine the HLA alleles of symptomatic and asymptomatic of COVID-19 patients using whole genome genotyping (Aim 2), and examine the T cell function in correlation with HLA-associated disease protection and susceptibility (Aim 3). The results are expected to provide a broader understanding of the genetic HLA association pertaining to the severity of COVID-19. Additionally, results should provide critical measures in performing HLA typing and virus detection to identify high risk individuals. Utilizing this finding, we may be able to prevent transmission and mitigate the impact of this disease in our dental, health care personnel, and other front-line professionals who are particularly susceptible to aerosol or droplet virus transmission.

COVID-19是由严重急性呼吸综合征 - 核纳病毒2（SARS-COV-2）的可疑人畜共患病源引起的。尽管冠状病毒（COV）相对普遍，但突变会导致人类严重的症状。 SARS-COV-2的挑战是：较长的孵化期（2-14天，中位5.1天），高病毒滴度，可以出现，而在Covid-19+患者是渐近的，以及它在其宿主之外的长时间，既可以在机载和表面上。据估计，截至2020年5月28日，212个国家 /地区的病例超过570万。症状的范围从轻度到重度，可能包括：发烧，沙发，呼吸急促，喉咙痛，疲劳，充血和寒意。在这些病例中，有13.8％的人需要进行医疗干预措施，有6％的患者悲惨地死亡，没有针对SARS-COV-2的可用疫苗。具有广泛的临床症状，更重要的是大量的渐近造成共证+患者，这是关于遗传易感性的关键问题，即人类白细胞抗原（HLA）是否在患者症状中起作用。初步的内部数据表明，特异性HLA与SARSCOV-2抗原具有结合亲和力，表明遗传HLA与COVID-19的临床症状是遗传性HLA的关联，我们假设“某些HLA等位基因或某些等位基因的组合可以用作同等等位基因的生物标志物，以实现COVID19的严重性。为了检验这一假设，我们建议使用硅内分析来定义主要的SARS-COV-2 T细胞抗原的HLA结合表位（AIM 1），确定使用整个基因组基因组分型的Covid-19患者的症状HLA等位基因和Covid-19患者的渐近等位基因（AIM 1）。 2），并检查与HLA相关疾病保护和易感性相关的T细胞功能（AIM 3）。预计结果将对与199的严重程度有关的遗传HLA关联提供更广泛的了解。此外，结果应为执行HLA打字和病毒检测提供关键措施以识别高风险个体。利用这一发现，我们可能能够防止传播和减轻这种疾病在我们的牙科医疗保健人员和其他前线专业人员中的影响，这些专业人员特别容易受到气溶胶或液滴病毒的传播。