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

新冠肺炎是由一种疑似严重急性呼吸系统综合症的人畜共患病源--冠状病毒-2引起的。虽然冠状病毒(CoV)相对常见，但变异可导致人类出现严重症状；SARS-CoV-2的挑战包括：潜伏期长(2-14天，中位数5.1天)，当新冠肺炎阳性患者没有症状时可能出现高病毒滴度，以及病毒在宿主外(空气中和表面)都能存活的长时间。据估计，截至2020年5月28日，212个国家有超过570万例病例。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、充血和寒战。在这些病例中，13.8%需要医疗干预，6%的患者悲惨死亡，没有可用的SARS-CoV-2疫苗。由于有广泛的临床症状，更重要的是有大量无症状的新冠肺炎+患者，因此关于遗传易感性的一个关键问题，即人类白细胞抗原(HLAs)是否在患者的症状中发挥作用。初步的电子计算机数据显示，特定的HLA与SARSCoV-2抗原具有结合亲和力，表明人类白细胞抗原与新冠肺炎临床症状存在遗传关联，这是本应用的主要目标。我们假设“某些等位基因或某些等位基因的组合可以作为新冠肺炎严重程度的生物标志物”。为了验证这一假设，我们建议使用电子计算机分析(Aim 1)定义主要SARS-CoV-2T细胞抗原的人类白细胞抗原结合表位(Aim 1)，使用全基因组基因分型方法(Aim 2)确定有症状和无症状的新冠肺炎患者的HLA等位基因，并检查T细胞功能与HLAs相关疾病预防和易感性的相关性(Aim 3)。这一结果有望为人们更广泛地了解与新冠肺炎严重程度有关的人类白细胞抗原的遗传关联。此外，结果应该为进行人类白细胞抗原配型和病毒检测以识别高危个体提供关键措施。利用这一发现，我们可能能够防止这种疾病的传播，并减轻这种疾病在我们的牙科、卫生保健人员和其他特别容易受到气雾剂或飞沫病毒传播的一线专业人员中的影响。

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.