Genetic underpinnings of dysosmia in COVID-19

Abstract entitled "Genetic underpinnings of dysosmia in COVID-19": There is evidence that smell and tastedysfunction is an early and often the only identifier in COVI-19 positive patients. We hypothesize that geneticvariants in specific candidate genes associated with the development of unique sensory phenotypes of COVID-19patients: In patients reported to the American Academy of Otolaryngology-Head and Neck Surgery using the COVID-19Anosmia Reporting Tool for Clinicians, in the first 237 entries anosmia was noted in 73% of patients prior to COVID-19diagnosis and was the initial symptom in 26.6%. The occurrence in asymptomatic individuals makes this finding a usefultarget for public health screening and would facilitate earlier diagnosis and treatment, as well as the identification of thoseindividuals who are not ill but still capable of spreading the disease. The mechanism underlying sensory alteration iscurrently unknown. Infectious diseases may demonstrate a heritable component - that is the propensity to contract anddevelop active infection and the severity of the immune response is influenced by host genetic factors to some extent andmay reflect inter-individual variation in the host immune response. The genetic basis of this variability in response willprovide important clues for therapeutics and lead to identification of groups at high risk of death. Public health measuresto identify those at increased genetic risk of severe infection would be useful as a way of mitigating the economic effectsof lockdown and social distancing policies. The genetic influence on COVID-19 symptoms may reflect genotype status ofcandidate genes such as ACE2 and TMPRSS2. Our team has been on the forefront to collect preliminary data on thepresence of neurosensory disturbances in COVID-19 patients. We and others reported that anosmia is an importantpredictive symptom of COVID-19. Moreover, a UK twin study has shown that anosmia in COVID-19 patients has a highheritability (h2 = 0.48), suggesting that an individual's genotype plays a role in the presence or absence of this symptom.The goal of this study is to determine the susceptibility which may be influenced by host genotype to sensory disorders inCOVID-19 patients to estimate the heritability of covid-19 sensory symptoms. In this study we will expand our work onfollowing Specific Aim: Identify genetic variation associated with the development of dysosmia in COVID-19patients. We hypothesize that there are genetic variants in the candidate genes that underlie smell and taste dysfunction inboth symptomatic and otherwise asymptomatic COVID-19 patients. Preliminary data: We have established aninternational interdisciplinary collaboration team and have collected and published preliminary data on the role of ENT inCOVID-19 and on the prevalence of sensory dysfunction in COVID-19 in our pilot studies. To determine if variants inspecific candidate genes are associated with the development of anosmia in COVID-19 patients, we will collect DNAsamples in our local COVID-19 patients and international patients from our collaborators for the study. In our hospitals,we have access to over 462 patients with confirmed positive COVID-19, 1565 with confirmed negative, and 390 patientswith pending testing results. Over 10% of these patients report smell and taste dysfunction; our international collaboratorshave a large cohort of COVID-19 patients with smell and taste dysfunction available to us as well (see their LOS). We willperform WES on 120 samples from COVID-19 patients including 60 with smell and taste dysfunction and 60 without. Wehave established a COVID19 blood sample treatment process at our pathology lab for our ongoing study. Whole exomesequencing will be performed using established methods in the Center for Genome Technology in the Hussman Institutefor Human Genomics (HIHG). Innovations in our proposal include: 1. Identify genetic markers for the early detectionof mild and asymptotic COVID-19. 2. Our minority focused Miami sensory screening and genomic screening pipeline,and a database of genomic variation and phenotypes - sensory disorders and COVID-19-positive people. 3. Amultidisciplinary, international collaboration with samples for duplicating studies.