Department of Microbiology, Medical School, National and Kapodistrian University of Athens, Athens, Greece.
Department of Otolaryngology, Head and Neck Surgery, Giessen University Hospital, Giessen, Germany.
Lifestyle Genom. 2024;17(1):42-56. doi: 10.1159/000539292. Epub 2024 May 15.
Olfactory dysfunction (OD) is not uncommon following viral infection. Herein, we explore the interplay of host genetics with viral correlates in coronavirus disease 2019 (COVID-19)- and long COVID-related OD, and its diagnosis and treatment that remain challenging. Two genes associated with olfaction, UGT2A1 and UGT2A2, appear to be involved in COVID-19-related anosmia, a hallmark symptom of acute infection with severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), particularly in the early stages of the pandemic. SARS-CoV-2 infects olfactory support cells, sustentacular and Bowman gland cells, that surround olfactory sensory neurons (OSNs) in the olfactory epithelium (OE) where the initial step of odor detection takes place. Anosmia primarily arises from the infection of support cells of the OE, followed by the deciliation and disruption of OE integrity, typically without OSN infection. Through the projected axons of OSNs, the virus could theoretically reach the olfactory bulb and brain, but current evidence points against this route. Intriguingly, SARS-CoV-2 infection of support cells leads to profound alterations in the nuclear architecture of OSNs, leading to the downregulation of odorant receptor-related genes, e.g., of Adcy3. Viral factors associated with the development of OD include spike protein aminoacidic changes, e.g., D614G, the first substitution that was selected early during SARS-CoV-2 evolution. More recent variants of the Omicron family are less likely to cause OD compared to Delta or Alpha, although OD has been associated with a milder disease course. OD is one of the most prevalent post-acute neurologic symptoms of SARS-CoV-2 infection. The tens of millions of people worldwide who have lingering problems with OD wait eagerly for effective new treatments that will restore their sense of smell which adds value to their quality of life.
嗅觉功能障碍（OD）在病毒感染后并不罕见。在此，我们探讨了宿主遗传学与 2019 年冠状病毒病（COVID-19）和与长期 COVID 相关的 OD 的病毒相关性之间的相互作用，以及其诊断和治疗仍然具有挑战性。与嗅觉相关的两个基因，UGT2A1 和 UGT2A2，似乎与 COVID-19 相关的嗅觉丧失有关，这是严重急性呼吸综合征冠状病毒 2（SARS-CoV-2）急性感染的标志性症状，特别是在大流行的早期阶段。SARS-CoV-2 感染嗅觉支持细胞、支持细胞和 Bowman 腺细胞，这些细胞环绕着发生气味检测初始步骤的嗅上皮（OE）中的嗅觉感觉神经元（OSN）。嗅觉丧失主要是由于 OE 的支持细胞感染引起的，随后 OSN 感染，OE 完整性的纤毛脱落和破坏。通过 OSN 的投射轴突，病毒理论上可以到达嗅球和大脑，但目前的证据反对这种途径。有趣的是，SARS-CoV-2 对支持细胞的感染导致 OSN 的核结构发生深刻改变，导致气味受体相关基因（例如，Adcy3）下调。与 OD 发展相关的病毒因素包括刺突蛋白氨基酸变化，例如，D614G，这是 SARS-CoV-2 进化早期选择的第一个取代。与 Delta 或 Alpha 相比，Omicron 家族的最新变体不太可能引起 OD，尽管 OD 与疾病较轻的病程有关。OD 是 SARS-CoV-2 感染后最常见的急性后神经系统症状之一。全球数以千万计的人长期存在 OD 问题，他们急切地等待有效的新治疗方法，以恢复他们的嗅觉，这为他们的生活质量增添了价值。
