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

COVID-19是由疑似严重急性呼吸综合征-冠状病毒-2 （SARS-CoV-2）的人畜共患源引起的。虽然冠状病毒（cov）相对常见，但突变会导致人类出现严重症状；SARS-CoV-2的挑战是：潜伏期长（2-14天，中位数5.1天），病毒滴度高（在COVID-19+患者无症状时可能出现），以及病毒在宿主外（空气传播和表面）存活的时间长。据估计，截至2020年5月28日，212个国家的病例超过570万例。症状从轻微到严重不等，可能包括：发烧、咳嗽、呼吸急促、喉咙痛、疲劳、充血和发冷。在这些病例中，有13.8%需要医疗干预，其中6%的患者死亡。可悲的是，没有针对SARS-CoV-2的可用疫苗。由于临床症状广泛，更重要的是无症状的COVID-19+患者群体众多，因此遗传易感性的关键问题是人类白细胞抗原（HLA）是否在患者的症状中发挥作用。初步的计算机数据显示特异性HLA与SARSCoV-2抗原的结合亲和力，表明HLA与COVID-19临床症状存在遗传关联，这是该应用的主要目的。我们假设“某个HLA等位基因或某些等位基因的组合可以作为COVID-19严重程度的生物标志物”。为了验证这一假设，我们提出使用计算机分析（Aim 1）从显性SARS-CoV-2 T细胞抗原中确定HLA结合表位，使用全基因组基因分型（Aim 2）确定有症状和无症状的COVID-19患者的HLA等位基因，并检测T细胞功能与HLA相关疾病保护和易感性的相关性（Aim 3）。这些结果有望为更广泛地了解与COVID-19严重程度相关的HLA基因关联提供帮助。此外，结果应提供进行HLA分型和病毒检测以识别高风险个体的关键措施。利用这一发现，我们可能能够预防传播并减轻这种疾病对我们的牙医、卫生保健人员和其他特别容易受到气溶胶或飞沫病毒传播的一线专业人员的影响。

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.