Background

The mechanisms by which any upper respiratory virus, including SARS-CoV-2, impairs chemosensory function are not known. COVID-19 is frequently associated with olfactory dysfunction after viral infection, which provides a research opportunity to evaluate the natural course of this neurological finding. Clinical trials and prospective and histological studies of new-onset post-viral olfactory dysfunction have been limited by small sample sizes and a paucity of advanced neuroimaging data and neuropathological samples. Although data from neuropathological specimens are now available, neuroimaging of the olfactory system during the acute phase of infection is still rare due to infection control concerns and critical illness and represents a substantial gap in knowledge.

Recent developments

The active replication of SARS-CoV-2 within the brain parenchyma (ie, in neurons and glia) has not been proven. Nevertheless, post-viral olfactory dysfunction can be viewed as a focal neurological deficit in patients with COVID-19. Evidence is also sparse for a direct causal relation between SARS-CoV-2 infection and abnormal brain findings at autopsy, and for trans-synaptic spread of the virus from the olfactory epithelium to the olfactory bulb. Taken together, clinical, radiological, histological, ultrastructural, and molecular data implicate inflammation, with or without infection, in either the olfactory epithelium, the olfactory bulb, or both. This inflammation leads to persistent olfactory deficits in a subset of people who have recovered from COVID-19. Neuroimaging has revealed localised inflammation in intracranial olfactory structures. To date, histopathological, ultrastructural, and molecular evidence does not suggest that SARS-CoV-2 is an obligate neuropathogen.

Where next?

The prevalence of CNS and olfactory bulb pathosis in patients with COVID-19 is not known. We postulate that, in people who have recovered from COVID-19, a chronic, recrudescent, or permanent olfactory deficit could be prognostic for an increased likelihood of neurological sequelae or neurodegenerative disorders in the long term. An inflammatory stimulus from the nasal olfactory epithelium to the olfactory bulbs and connected brain regions might accelerate pathological processes and symptomatic progression of neurodegenerative disease. Persistent olfactory impairment with or without perceptual distortions (ie, parosmias or phantosmias) after SARS-CoV-2 infection could, therefore, serve as a marker to identify people with an increased long-term risk of neurological disease.

中文翻译：

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COVID-19 对嗅觉系统的后病毒效应及其影响

背景

任何上呼吸道病毒（包括 SARS-CoV-2）损害化学感觉功能的机制尚不清楚。COVID-19 经常与病毒感染后的嗅觉功能障碍有关，这为评估这一神经学发现的自然过程提供了研究机会。新发病毒后嗅觉功能障碍的临床试验和前瞻性和组织学研究受到小样本量和缺乏高级神经影像学数据和神经病理学样本的限制。尽管现在可以获得来自神经病理学标本的数据，但由于感染控制问题和危重疾病，感染急性期嗅觉系统的神经影像学检查仍然很少见，这代表了知识上的巨大差距。

近期发展

SARS-CoV-2 在脑实质内（即在神经元和神经胶质细胞中）的主动复制尚未得到证实。然而，病毒后嗅觉功能障碍可被视为 COVID-19 患者的局灶性神经功能障碍。SARS-CoV-2 感染与尸检时大脑异常发现之间存在直接因果关系，以及病毒从嗅上皮细胞跨突触传播到嗅球的证据也很少。总而言之，临床、放射学、组织学、超微结构和分子数据表明嗅上皮细胞、嗅球或两者都有炎症，伴或不伴感染。这种炎症会导致一部分从 COVID-19 中康复的人出现持续的嗅觉缺陷。神经影像学显示颅内嗅觉结构存在局部炎症。

接下来呢？

COVID-19 患者中枢神经系统和嗅球病变的患病率尚不清楚。我们假设，在从 COVID-19 康复的人群中，慢性、复发性或永久性嗅觉缺陷可能预示着神经系统后遗症或神经退行性疾病的长期可能性增加。从鼻嗅觉上皮细胞到嗅球和相连的大脑区域的炎症刺激可能会加速神经退行性疾病的病理过程和症状进展。因此，SARS-CoV-2 感染后伴有或不伴有知觉扭曲（即嗅觉异常或幻嗅）的持续性嗅觉障碍可以作为识别神经系统疾病长期风险增加的人的标志。