The neurotropism of human coronaviruses has already been demonstrated in small animals, and in autoptic studies the severe acute respiratory syndrome coronavirus (SARS-CoV), which was responsible for the SARS outbreak during 2002 to 2003, was found in the brains of patients with infection.¹ It has been proposed that the neuroinvasive potential of the novel SARS-CoV-2, responsible for coronavirus disease 2019 (COVID-19), may be at least partially responsible for the respiratory failure of patients with COVID-19.² In this article, we share the magnetic resonance imaging (MRI) evidence of in vivo brain alteration presumably due to SARS-CoV-2 and demonstrate that anosmia can represent the predominant symptom in COVID-19.

A 25-year-old female radiographer with no significant medical history who had been working in a COVID-19 ward presented with a mild dry cough that lasted for 1 day, followed by persistent severe anosmia and dysgeusia. She did not have a fever. She had no trauma, seizure, or hypoglycemic event. Three days later, nasal fibroscopic evaluation results were unremarkable, and noncontrast chest and maxillofacial computed tomography results were negative. On the same day, a brain MRI was also performed. On 3-dimensional and 2-dimensional fluid-attenuated inversion recovery images, a cortical hyperintensity was evident in the right gyrus rectus (Figure 1) and a subtle hyperintensity was present in the olfactory bulbs (Figure 1). Because many patients in Italy are experiencing anosmia³ and the cortical signal alteration was suggestive of viral infection, a swab test was performed and reverse transcription–polymerase chain reaction analysis yielded positive results for SARS-CoV-2. During a follow-up MRI performed 28 days later, the signal alteration in the cortex completely disappeared and the olfactory bulbs were thinner and slightly less hyperintense (Figure 2⁴). The patient recovered from anosmia. No brain abnormalities were seen in 2 other patients with COVID-19 presenting anosmia who underwent brain MRI 12 and 25 days from symptom onset.

To our knowledge, this is the first report of in vivo human brain involvement in a patient with COVID-19 showing a signal alteration compatible with viral brain invasion in a cortical region (ie, posterior gyrus rectus) that is associated with olfaction. Alternative diagnoses (eg, status epilepticus, posterior reversible encephalopathy syndrome–like alterations, other viral infections, and anti–N-methyl-d-aspartate receptor encephalitis) are unlikely given the clinical context. Based on the MRI findings, including the slight olfactory bulb changes, we can speculate that SARS-CoV-2 might invade the brain through the olfactory pathway and cause an olfactory dysfunction of sensorineural origin; cerebrospinal fluid and pathology studies are required to confirm this hypothesis. Ours and others’ observations of normal brain imaging in other patients with COVID-19–associated olfactory dysfunctions⁴ and the disappearance of the cortical MRI abnormalities in the follow-up study of this patient suggest that imaging changes are not always present in COVID-19 or might be limited to the very early phase of the infection. Further, anosmia can be the predominant COVID-19 manifestation, and this should be considered for the identification and isolation of patients with infection to avoid disease spread.

人类冠状病毒的嗜神经性已经在小型动物中得到证实，在尸体研究中，感染患者的大脑中发现了严重急性呼吸综合征冠状病毒（SARS-CoV），该病毒是2002年至2003年间SARS爆发的原因。 。¹有人提出，新型SARS-CoV-2在2019年冠状病毒疾病（COVID-19）的神经入侵潜力可能至少部分负责COVID-19患者的呼吸衰竭。²在本文中，我们分享了可能归因于SARS-CoV-2的体内脑部改变的磁共振成像（MRI）证据，并证明了嗅觉障碍可以代表COVID-19中的主要症状。

一名25岁的女性射线照相术医师，没有明显的病史，曾在COVID-19病房工作，出现轻度干咳，持续了1天，之后持续出现严重的失眠和消化不良。她没有发烧。她没有外伤，癫痫发作或低血糖事件。三天后，鼻纤维镜检查结果未见异常，胸部和颌面计算机断层扫描的非造影结果为阴性。在同一天，还进行了脑部MRI检查。在3维和2维流体衰减的反转恢复图像上，右回直肌明显可见皮质高强度（图1），嗅球中存在微妙的高强度（图1）。因为意大利的许多患者都患有失眠症³并且皮质信号改变提示病毒感染，进行了拭子测试，逆转录聚合酶链反应分析对SARS-CoV-2产生了阳性结果。在28天后进行的MRI随访中，皮层中的信号改变完全消失，嗅球变薄，高信号稍弱（图2 ⁴）。病人从失眠中康复。在出现症状的第12天和第25天接受脑MRI检查的另外2例出现嗅觉异常的COVID-19患者中未见脑异常。

据我们所知，这是第一例体内人脑受累于COVID-19的患者的报告，显示与嗅觉相关的皮质区域（即后回直肌）中与病毒性脑浸润相容的信号改变。其他诊断（例如，癫痫持续状态，后可逆脑病综合征样的改变，其它病毒感染，和抗Ñ甲基d鉴于临床情况，天冬氨酸受体脑炎是不可能的。根据MRI的发现，包括轻微的嗅球变化，我们可以推测SARS-CoV-2可能通过嗅觉途径侵入大脑，并导致嗅觉功能障碍。需要进行脑脊液和病理学研究以证实这一假设。我们和其他人在其他COVID-19相关性嗅觉功能障碍患者中的​​正常脑部影像学观察⁴并且该患者的随访研究中皮质MRI异常的消失提示，COVID-19并不总是存在影像学改变，或者可能仅限于感染的早期阶段。此外，嗅觉障碍可能是COVID-19的主要表现形式，应将其用于识别和隔离感染患者以避免疾病传播。