Mechanisms of long-term taste loss in post-acute sequelae of COVID-19

COVID-19急性后遗症导致长期味觉丧失的机制

基本信息

批准号：
10554842
负责人：
Hong Wang
金额：
$ 42.33万
依托单位：
MONELL CHEMICAL SENSES CENTER
依托单位国家：
美国
项目类别：
财政年份：
2021
资助国家：
美国
起止时间：
2021-04-01 至 2026-03-31
项目状态：
未结题

来源：
https://reporter.nih.gov/project-details/10554842
关键词：
2019-nCoV ACE2 Acute Administrative Supplement Affect Ageusia American Animal Model Anxiety Award Body Weight decreased COVID-19 COVID-19 patient COVID-19 severity Cell Death Cell Differentiation process Cells Colorado Defect Disease Environmental Risk Factor Exhibits Failure Functional disorder Future Genes Genetic Goals Grant Health High Prevalence Human IFNAR1 gene IL8 gene IRF3 gene Immune response Immunology In Vitro Infection Inflammation Inflammatory Injury Interferon Type I Interferons Interleukin-18 Interleukin-6 Knock-in Knock-out Knockout Mice Lead Longevity Malnutrition Mediating Mental Depression Molecular Mucous Membrane Mus Mutation Natural regeneration Newborn Infant Organoids Paper Pathologic Pathway interactions Patients Personal Satisfaction Persons Play Positioning Attribute Post-Acute Sequelae of SARS-CoV-2 Infection Process Proliferating Publishing Quality of life Recovery Reporting Research Research Personnel Role SARS-CoV-2 infection Saliva Severities Signaling Protein Structure of parenchyma of lung Symptoms TLR3 gene TNF gene Taste Bud Cell Taste Buds Taste Disorders Taste Perception Testing Therapeutic Intervention Tissues Toll-like receptors Universities Viral Virus Diseases body system cell regeneration cytokine effective therapy in vivo evaluation insight lung injury mouse model nerve supply pathogenic virus post-COVID-19 progenitor public health relevance receptor regeneration model severe COVID-19 stem cells therapy development treatment strategy type I interferon receptor

项目摘要

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.

项目概要 SARS-CoV-2 已感染全球超过 3.4 亿人，其中约 40-45% 是美国人。这些患者报告了味觉异常，虽然许多患者的味觉功能很快恢复，最近的研究表明，大约 10-20% 的患者患有持续时间超过 6 小时的持续味觉丧失。长期味觉丧失会严重影响健康——降低生活质量并导致目前，长期味觉丧失的机制与营养不良、焦虑和抑郁有关。人们对 COVID-19 感染知之甚少，也没有有效的治疗方法。治疗策略时，有必要确定哪些因素导致长期味觉丧失。抗病毒机制已经发展到可以保护我们免受大量病毒病原体的侵害。最近的研究表明，先天遗传因素可能会削弱这种机制。一些抗病毒基因的错误导致了 COVID-19 的严重性，但这些基因错误也导致严重、长期味觉丧失的原因尚不清楚。在这项研究中，我们将使用动物模型来模拟。抗病毒途径中存在先天性遗传错误的患者，专门研究这些错误是否以及如何发生遗传缺陷是否会导致急性 COVID-19 后的长期味觉丧失。我们将进一步确定是否会导致这种情况。宿主免疫反应中的哪些炎症因子抑制味蕾再生，从而有助于这项研究中发现的持续味觉丧失的机制也可能适用于其他疾病的长期症状。器官系统并有助于开发长期化学感觉丧失的治疗方法。