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

ABSTRACTCOVID-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 inhumans; the challenges of SARS-CoV-2 are: the long incubation period (2-14 days, median 5.1 days), high viraltiter which can appear while a COVID-19+ patient is asymptomatic, and the long period of time in which it isviable outside of its host, both airborne and on surfaces. It is estimated as of May 28, 2020, that there are over5.7 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 medicalinterventions, with 6% of patients dying Tragically, there are no available vaccines against SARS-CoV-2. Witha 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 inthe patient symptomology. Preliminary in-silico data have revealed binding affinity of specific HLAs to SARS-CoV-2 antigens, indicating a genetic HLA association with COVID-19 clinical symptoms, which is the primaryobjective of this application. We hypothesize that "A certain HLA allele or combination of certain alleles canserve as biomarker for the severity of COVID-19". To test this hypothesis, we propose to define HLA bindingepitopes from dominant SARS-CoV-2 T cell antigens using in-silico analysis (Aim 1), determine the HLAalleles of symptomatic and asymptomatic of COVID-19 patients using whole genome genotyping (Aim2), and examine the T cell function in correlation with HLA-associated disease protection andsusceptibility (Aim 3). The results are expected to provide a broader understanding of the genetic HLAassociation pertaining to the severity of COVID-19. Additionally, results should provide critical measures inperforming HLA typing and virus detection to identify high risk individuals. Utilizing this finding, we may be ableto prevent transmission and mitigate the impact of this disease in our dental, health care personnel, and otherfront-line professionals who are particularly susceptible to aerosol or droplet virus transmission.