entitled ?Genetic underpinnings of dysosmia in COVID-19?: There is evidence that smell and taste dysfunction is an early and often the only identifier in COVI-19 positive patients. We hypothesize that genetic variants in specific candidate genes associated with the development of unique sensory phenotypes of COVID-19 patients: In patients reported to the American Academy of Otolaryngology-Head and Neck Surgery using the COVID-19 Anosmia Reporting Tool for Clinicians, in the first 237 entries anosmia was noted in 73% of patients prior to COVID-19 diagnosis and was the initial symptom in 26.6%. The occurrence in asymptomatic individuals makes this finding a useful target for public health screening and would facilitate earlier diagnosis and treatment, as well as the identification of those individuals who are not ill but still capable of spreading the disease. The mechanism underlying sensory alteration is currently unknown. Infectious diseases may demonstrate a heritable component ? that is the propensity to contract and develop active infection and the severity of the immune response is influenced by host genetic factors to some extent and may reflect inter-individual variation in the host immune response. The genetic basis of this variability in response will provide important clues for therapeutics and lead to identification of groups at high risk of death. Public health measures to identify those at increased genetic risk of severe infection would be useful as a way of mitigating the economic effects of lockdown and social distancing policies. The genetic influence on COVID-19 symptoms may reflect genotype status of candidate genes such as ACE2 and TMPRSS2. Our team has been on the forefront to collect preliminary data on the presence of neurosensory disturbances in COVID-19 patients. We and others reported that anosmia is an important predictive symptom of COVID-19. Moreover, a UK twin study has shown that anosmia in COVID-19 patients has a high heritability (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 in COVID-19 patients to estimate the heritability of covid-19 sensory symptoms. In this study we will expand our work on following Specific Aim: Identify genetic variation associated with the development of dysosmia in COVID-19 patients. We hypothesize that there are genetic variants in the candidate genes that underlie smell and taste dysfunction in both symptomatic and otherwise asymptomatic COVID-19 patients. Preliminary data: We have established an international interdisciplinary collaboration team and have collected and published preliminary data on the role of ENT in COVID-19 and on the prevalence of sensory dysfunction in COVID-19 in our pilot studies. To determine if variants in specific candidate genes are associated with the development of anosmia in COVID-19 patients, we will collect DNA samples 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 patients with pending testing results. Over 10% of these patients report smell and taste dysfunction; our international collaborators have a large cohort of COVID-19 patients with smell and taste dysfunction available to us as well (see their LOS). We will perform WES on 120 samples from COVID-19 patients including 60 with smell and taste dysfunction and 60 without. We have established a COVID19 blood sample treatment process at our pathology lab for our ongoing study. Whole exome sequencing will be performed using established methods in the Center for Genome Technology in the Hussman Institute for Human Genomics (HIHG). Innovations in our proposal include: 1. Identify genetic markers for the early detection of 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. A multidisciplinary, international collaboration with samples for duplicating studies.

Public Health Relevance

The goal of the study is to identify genetic variation associated with the development of dysosmia in COVID-19 patients. We will look for genetic variants in specific candidate genes associated with the development of unique sensory phenotypes of COVID-19 patients as early and mild/only identifier.

Agency
National Institute of Health (NIH)
Institute
National Institute on Deafness and Other Communication Disorders (NIDCD)
Type
Research Project (R01)
Project #
3R01DC005575-19S1
Application #
10177502
Study Section
Genetics of Health and Disease Study Section (GHD)
Program Officer
Watson, Bracie
Project Start
2001-09-15
Project End
2022-08-31
Budget Start
2020-09-01
Budget End
2021-08-31
Support Year
19
Fiscal Year
2020
Total Cost
Indirect Cost
Name
University of Miami School of Medicine
Department
Otolaryngology
Type
Schools of Medicine
DUNS #
052780918
City
Coral Gables
State
FL
Country
United States
Zip Code
33146
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Wang, Li; Yan, Denise; Qin, Litao et al. (2018) Amino acid 118 in the Deafness Causing (DFNA20/26) ACTG1 gene is a Mutational Hot Spot. Gene Rep 11:264-269
Mittal, Rahul; Bencie, Nicole; Parrish, James M et al. (2018) An Update on Phosphodiesterase Mutations Underlying Genetic Etiology of Hearing Loss and Retinitis Pigmentosa. Front Genet 9:9
Snapp, Hillary A; Hoffer, Michael E; Liu, Xuezhong et al. (2017) Effectiveness in Rehabilitation of Current Wireless CROS Technology in Experienced Bone-Anchored Implant Users. Otol Neurotol 38:1397-1404
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Mittal, Rahul; Nguyen, Desiree; Patel, Amit P et al. (2017) Recent Advancements in the Regeneration of Auditory Hair Cells and Hearing Restoration. Front Mol Neurosci 10:236
Kim, So Young; Kim, Ah Reum; Kim, Nayoung K D et al. (2016) Functional characterization of a novel loss-of-function mutation of PRPS1 related to early-onset progressive nonsyndromic hearing loss in Koreans (DFNX1): Potential implications on future therapeutic intervention. J Gene Med 18:353-358
Manzoli, Gabrielle N; Bademci, Guney; Acosta, Angelina X et al. (2016) Targeted Resequencing of Deafness Genes Reveals a Founder MYO15A Variant in Northeastern Brazil. Ann Hum Genet 80:327-331
Mittal, Rahul; Grati, M'hamed; Yan, Denise et al. (2016) Pseudomonas aeruginosa Activates PKC-Alpha to Invade Middle Ear Epithelial Cells. Front Microbiol 7:255
Mittal, Rahul; Grati, M'hamed; Sedlacek, Miloslav et al. (2016) Characterization of ATPase Activity of P2RX2 Cation Channel. Front Physiol 7:186

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