Document text
Principal Investigator: Hong Wang
Organization: MONELL CHEMICAL SENSES CENTER
Fiscal Year: 2022
Award: $423,308
Funding agency: National Institute on Deafness and Other Communication Disorders
PROJECT SUMMARY
SARS-CoV-2 has infected >340 million people worldwide, including >70 million Americans. Roughly 40-45% of
these patients have reported taste abnormalities. While taste function is restored quickly in many patients,
recent studies show that about 10-20% of patients suffer from sustained taste loss that lasts longer than 6
months. Long-term taste loss significantly impacts health – decreasing quality of life and contributing to
malnutrition, anxiety, and depression. Currently, the mechanism of long-term taste loss associated with
COVID-19 infection is poorly understood, and there is no effective treatment for it. In order to develop
treatment strategies, it is necessary to determine what factors contribute to long-term taste loss. Multiple
antiviral mechanisms have evolved to protect us from the vast number of viral pathogens. However, these
mechanisms can be weakened by genetic or environmental factors. Recent studies show that inborn genetic
errors in some antiviral genes contribute to the severity of COVID-19, but whether these genetic errors also
contribute to severe, long-term taste loss is unknown. In this study, we will use animal models to simulate
patients with inborn genetic errors in antiviral pathways to specifically investigate whether and how these
genetic defects contribute to long-term taste loss after acute COVID-19. We will further determine whether and
which inflammatory factors in host immune responses inhibit taste bud regeneration and thus contribute to
sustained taste loss. Mechanisms identified in this study may also apply to long-lasting symptoms in other
organ systems and help to develop treatments for long-term chemosensory loss.
Terms: <(TNF)-α><0-4 weeks old><2019 novel corona virus><2019 novel coronavirus><2019-nCoV><3-10C><ACE2><AMCF-I><Acute><Administrative Supplement><Affect><Ageusia><Alpha-Beta-Omega Interferon Receptor-1><American><Animal Model><Animal Models and Related Studies><Antiviral Protein Alpha Type><Anxiety><Award><B cell differentiation factor><B cell stimulating factor 2><B-Cell Differentiation Factor><B-Cell Differentiation Factor-2><B-Cell Stimulatory Factor-2><BCDF><BSF-2><BSF2><Body Tissues><Body Weight decreased><COVID disease severity><COVID infected patient><COVID patient><COVID positive patient><COVID severity><COVID-19><COVID-19 disease severity><COVID-19 infected patient><COVID-19 infection><COVID-19 patient><COVID-19 positive patient><COVID-19 severity><COVID-19 virus><COVID19><COVID19 disease severity><COVID19 infection><COVID19 patient><COVID19 positive patient><COVID19 severity><COVID19 virus><CV-19><CV19><CXCL8><Cachectin><Cell Body><Cell Death><Cell Differentiation><Cell Differentiation process><Cells><CoV-2><CoV2><Colorado><Defect><Disease><Disorder><Dysfunction><Environmental Factor><Environmental Risk Factor><Exhibits><Failure><Functional disorder><Future><GCP1><Genes><Genetic><Genetic Alteration><Genetic Change><Genetic defect><Goals><Grant><Gustation><HPGF><Health><Hepatocyte-Stimulating Factor><High Prevalence><HuIFN-Alpha-Rec><Human><Hybridoma Growth Factor><IFN><IFN-beta 2><IFN-gamma-Inducing Factor><IFN-regulatory factor 3><IFNAR><IFNAR1><IFNAR1 gene><IFNB2><IFNBR><IFRC><IGIF><IL-1 Gamma><IL-18><IL-1g><IL-6><IL-8><IL18 Protein><IL1F4><IL6 Protein><IL8><IL8 gene><IRF-3 protein><IRF3><IRF3 gene><Immune response><Immunological response><Immunology><In Vitro><Infection><Inflammation><Inflammatory><Injury><Interferon Alpha-Beta Receptor Alpha Chain><Interferon Regulatory Factor 3><Interferon Type I><Interferon-gamma-Inducing Factor><Interferons><Interleukin 18 (Interferon-Gamma-Inducing Factor)><Interleukin 18 Proprotein><Interleukin-1 Gamma><Interleukin-18><Interleukin-18 Precursor><Interleukin-6><Investigators><K60><KO mice><Knock-in><Knock-out><Knock-out Mice><Knockout><Knockout Mice><Lead><Length of Life><Longevity><Lung Parenchyma><Lung Tissue><Lung damage><MGC12320><MGI-2><Macrophage-Derived TNF><Malnutrition><Mediating><Mental Depression><Mice><Mice Mammals><Modern Man><Molecular><Monocyte-Derived TNF><Mucosa><Mucosal Tissue><Mucous Membrane><Murine><Mus><Mutation><Myeloid Differentiation-Inducing Protein><Natural regeneration><Newborn Infant><Newborns><Null Mouse><Nutritional Deficiency><Organ System><Organoids><PASC><Paper><Pathologic><Pathway interactions><Patients><Pb element><Personal Satisfaction><Persons><Physiopathology><Plasmacytoma Growth Factor><Play><Position><Positioning Attribute><Post Acute Sequelae of COVID19><Post Acute Sequelae of SARS-CoV-2><Post Acute Sequelae of SARS-CoV2><Post Acute Sequelae of severe acute respiratory syndrome coronavirus 2><Post-Acute Sequelae of SARS-CoV-2 Infection><Process><Progenitor Cells><Proliferating><Publishing><QOL><Quality of life><Receptor Protein><Recovery><Regeneration><Reporting><Research><Research Personnel><Researchers><Role><SARS corona virus 2><SARS-CO-V2><SARS-COVID-2><SARS-CoV-2><SARS-CoV-2 disease severity><SARS-CoV-2 infected patient><SARS-CoV-2 infection><SARS-CoV-2 patient><SARS-CoV-2 positive patient><SARS-CoV-2 severity><SARS-CoV2><SARS-CoV2 infection><SARS-associated corona virus 2><SARS-associated coronavirus 2><SARS-coronavirus-2><SARS-related corona virus 2><SARS-related coronavirus 2><SARSCoV2><SCYB8><Saliva><Severe Acute Respiratory Coronavirus 2><Severe Acute Respiratory Distress Syndrome CoV 2><Severe Acute Respiratory Distress Syndrome Corona Virus 2><Severe Acute Respiratory Distress Syndrome Coronavirus 2><Severe Acute Respiratory Syndrome CoV 2><Severe Acute Respiratory Syndrome-associated coronavirus 2><Severe Acute Respiratory Syndrome-related coronavirus 2><Severe acute respiratory syndrome associated corona virus 2><Severe acute respiratory syndrome corona virus 2><Severe acute respiratory syndrome coronavirus 2><Severe acute respiratory syndrome coronavirus 2 infection><Severe acute respiratory syndrome related corona virus 2><Severities><Signaling Factor Proto-Oncogene><Signaling Pathway Gene><Signaling Protein><Structure of parenchyma of lung><Symptoms><TLR protein><TLR3><TLR3 gene><TNF><TNF A><TNF Alpha><TNF gene><TNF-α><TNFA><TNFα><TSG-1><Taste><Taste Bud Cell><Taste Buds><Taste Disorders><Taste Perception><Testing><Therapeutic Intervention><Tissues><Toll-Like Receptor 3><Toll-Like Receptor Family Gene><Toll-like receptors><Tumor Necrosis Factor><Tumor Necrosis Factor-alpha><Undernutrition><Universities><Viral><Viral Diseases><Virus Diseases><Weight Loss><Weight Reduction><Wuhan coronavirus><adverse sequelae of COVID><adverse sequelae of COVID-19><adverse sequelae of coronavirus disease><adverse sequelae of coronavirus disease 2019><angiotensin converting enzyme 2><angiotensin converting enzyme II><b-ENAP><body system><body weight loss><cell regeneration><cellular regeneration><chronic COVID-19 sequelae><corona virus disease 2019><coronavirus disease 2019><coronavirus disease 2019 disease severity><coronavirus disease 2019 infected patient><coronavirus disease 2019 infection><coronavirus disease 2019 patient><coronavirus disease 2019 positive patient><coronavirus disease 2019 severity><coronavirus disease 2019 virus><coronavirus disease infected patient><coronavirus disease patient><coronavirus disease positive patient><coronavirus disease severity><coronavirus disease-19><coronavirus disease-19 patient><coronavirus disease-19 virus><coronavirus infectious disease-19><coronavirus patient><cytokine><depression><develop therapy><dietary deficiency><effective therapy><effective treatment><environmental risk><genome mutation><gustatory perception><gustatory processing><gustatory response><hCoV19><heavy metal Pb><heavy metal lead><host response><ifnar1 gene product><immune system response><immunoresponse><in vivo evaluation><in vivo testing><infected with COVID-19><infected with COVID19><infected with SARS-CoV-2><infected with SARS-CoV2><infected with coronavirus disease 2019><infected with severe acute respiratory syndrome coronavirus 2><injuries><innervation><insight><interferon beta 2><intervention development><intervention therapy><knockin><life span><life-threatening COVID><life-threatening COVID-19><life-threatening SARS-CoV-2><life-threatening coronavirus disease><life-threatening coronavirus disease 2019><life-threatening severe acute respiratory syndrome coronavirus 2><lifespan><long haul sequelae of COVID-19><long haul sequelae of coronavirus disease 2019><long-term sequelae of COVID-19><long-term sequelae of SARS-CoV-2><long-term sequelae of coronavirus disease 2019><long-term sequelae of severe acute respiratory syndrome coronavirus 2><lung injury><malnourished><model of animal><model organism><mouse model><murine model><nCoV2><necrocytosis><nerve supply><newborn child><newborn children><nutrition deficiency><nutrition deficiency disorder><nutritional deficiency disorder><pathogenic virus><pathophysiology><pathway><patient infected with COVID><patient infected with COVID-19><patient infected with SARS-CoV-2><patient infected with coronavirus disease><patient infected with coronavirus disease 2019><patient infected with severe acute respiratory syndrome coronavirus 2><patient with COVID><patient with COVID-19><patient with COVID19><patient with SARS-CoV-2><patient with coronavirus disease><patient with coronavirus disease 2019><patient with severe acute respiratory distress syndrome coronavirus 2><post-COVID><post-COVID-19><post-acute sequelae following SARS-CoV-2 infection><post-acute sequelae of COVID-19><post-acute sequelae of acute COVID infection><post-acute sequelae of coronavirus disease 2019><post-coronavirus disease 2019><progenitor><public health relevance><pulmonary damage><pulmonary injury><pulmonary tissue damage><pulmonary tissue injury><receptor><regenerate><regeneration model><regenerative model><serious COVID><serious COVID-19><serious SARS-CoV-2><serious coronavirus disease><serious coronavirus disease 2019><serious severe acute respiratory syndrome coronavirus 2><severe COVID><severe COVID-19><severe COVID19><severe SARS-CoV-2><severe acute respiratory syndrome coronavirus 2 disease severity><severe acute respiratory syndrome coronavirus 2 infected patient><severe acute respiratory syndrome coronavirus 2 patient><severe acute respiratory syndrome coronavirus 2 positive patient><severe acute respiratory syndrome coronavirus 2 severity><severe coronavirus disease><severe coronavirus disease 19><severe coronavirus disease 2019><severe severe acute respiratory syndrome coronavirus 2><social role><stem cells><taste loss><taste processing><taste receptor><taste response><therapy development><treatment development><treatment strategy><type I IFN receptor><type I interferon receptor><viral infection><viral pathogen><virus infection><virus pathogen><virus-induced disease><well-being><wellbeing><wt-loss>