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

项目摘要 SARS-CoV-2已感染全球超过3.4亿人，其中包括超过7000万美国人。大约40-45% 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%的患者患有持续的味觉丧失，持续时间超过6 个月长期味觉丧失会显著影响健康-降低生活质量， 营养不良焦虑和抑郁目前，长期味觉丧失的机制与 人们对COVID-19感染知之甚少，也没有有效的治疗方法。为了开发 治疗策略，有必要确定哪些因素导致长期味觉丧失。多 抗病毒机制已经发展到保护我们免受大量病毒病原体的侵害。但这些 遗传或环境因素会削弱这些机制。最近的研究表明， 一些抗病毒基因的错误会导致COVID-19的严重性，但这些遗传错误是否也 导致严重的，长期的味觉丧失是未知的。在本研究中，我们将使用动物模型来模拟 在抗病毒途径中存在先天性遗传错误的患者，以专门研究这些基因是否以及如何在 遗传缺陷导致急性COVID-19后长期味觉丧失。我们将进一步确定是否和 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 持续的味觉丧失这项研究中确定的机制也可能适用于其他慢性疾病的长期症状。 器官系统，并帮助开发长期化学感觉丧失的治疗方法。

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.