One relevant feature of the Covid‐19 disease is the absence of dyspnea, described as ‘shortness of breath’ or ‘an unpleasant urge to breathe’. The lack of dyspnea is observed even in the most severe cases, in which subjects present tachypnea and tachycardia. In the Wuhan cohort, 62.4% of severe cases and 46.3% of those who ended up intubated, ventilated or dead did not present dyspnea [1, 2.

Similar findings have been reported in the severe acute respiratory syndrome coronavirus (SARS‐CoV) infection where only 34.8% of critical patients reported dyspnea. These data differ significantly from other viral pulmonary infections where the presence of dyspnea is much more frequent, i.e. 69% in Severe acute respiratory syndrome—middle East respiratory syndrome, 95% in respiratory syncytial virus and 82% in influenza [3.

Dyspnea is a multidimensional cognitive construct of respiratory sensation, resulting from peripheral afferences and processed through the brainstem to subcortical and supratentorial structures. Peripheral afferent fibers are located in the lungs and airways; they respond to chemical and mechanical stimuli and drive physiological responses such as cough, tachypnea and dyspnea. The afferent fibers that appear to play the most relevant role in dyspnea are the pulmonary C‐fibers, which are predominantly located below the alveolar membrane. The chemical activation of these C‐fibers (histamine, adenosine, prostaglandine E2 or lobeline) causes dyspnea or intensifies it and their inhibition (inhaled furosemide) suppresses it.

Although local changes in viral pneumonia could stimulate C‐pulmonary fibers, the cytokine storm syndrome (which is rather characteristic of Covid‐19) could damage these neurons and therefore explain a total or partial loss of their function. However, this hypothesis collides with the fact that some viral respiratory infections induce an upregulation of receptors from these afferent sensory fibers [4.

For many viruses, the olfactory bulb is the gateway to the central nervous system. In particular, hyposmia has been observed in patients with Covid‐19 [5. Furthermore, experimental findings show that SARS‐CoV enters the central nervous system via the olfactory bulb. It rapidly spreads to other regions, causing neuronal death and affecting the nucleus of the solitary tract (where pulmonary C‐fibers are projected) on the fourth day since the onset of the infection [6. It is important to point out that there are other structures that participate in the sensory perception of dyspnea that are affected before the involvement of the nucleus of the solitary tract (i.e. thalamus, insula and limbic system).

However, whereas other neurological manifestations of the central nervous system [5 have been described, such as dizziness, we must be cautious in attributing those symptoms to a direct neurotoxic effect of the virus rather than a systemic response in the infectious context.

The emerging situation of a global epidemic of Covid‐19 has presented many challenges in a wide variety of disciplines from science to the economy. Neurologists should not ignore the questions raised by this novel coronavirus and we must be prepared to answer them. This is why now, more than ever, what Gandalf once (almost) said remains valid: “A neurologist is never late, nor is he early, he arrives precisely when he means to.”

Covid-19 疾病的一个相关特征是没有呼吸困难，被描述为“呼吸急促”或“令人不快的呼吸冲动”。即使在受试者出现呼吸急促和心动过速的最严重病例中也观察到没有呼吸困难。在武汉队列中，62.4% 的重症病例和 46.3% 的最终插管、通气或死亡病例没有出现呼吸困难 [ 1, 2 .

在严重急性呼吸综合征冠状病毒 (SARS-CoV) 感染中也有类似的发现，其中只有 34.8% 的危重患者报告呼吸困难。这些数据与其他病毒性肺部感染明显不同，其他病毒性肺部感染更频繁地​​出现呼吸困难，即 69% 的严重急性呼吸综合征 - 中东呼吸综合征、95% 的呼吸道合胞病毒和 82% 的流感 [ 3 ] 。

呼吸困难是呼吸感觉的多维认知结构，由外周感觉产生并通过脑干处理到皮层下和幕上结构。外周传入纤维位于肺和气道；它们对化学和机械刺激作出反应，并驱动诸如咳嗽、呼吸急促和呼吸困难等生理反应。似乎在呼吸困难中起最相关作用的传入纤维是肺 C 纤维，主要位于肺泡膜下方。这些 C 纤维（组胺、腺苷、前列腺素 E2 或山叶碱）的化学活化会导致呼吸困难或加剧呼吸困难，而它们的抑制作用（吸入呋塞米）会抑制它。

尽管病毒性肺炎的局部变化可以刺激 C 肺纤维，但细胞因子风暴综合征（这是 Covid-19 的特征）可能会损害这些神经元，因此可以解释它们的全部或部分功能丧失。然而，这一假设与一些病毒性呼吸道感染诱导这些传入感觉纤维的受体上调的事实相矛盾 [ 4 ] 。

对于许多病毒来说，嗅球是通往中枢神经系统的门户。特别是在 Covid-19 患者中观察到嗅觉减退 [ 5 . 此外，实验结果表明，SARS-CoV 通过嗅球进入中枢神经系统。自感染开始后的第四天，它迅速扩散到其他区域，导致神经元死亡并影响孤束核（肺 C 纤维投射的地方）[ 6 . 需要指出的是，在孤立束核（即丘脑、岛叶和边缘系统）受累之前，还有其他参与呼吸困难感觉知觉的结构受到影响。

然而，虽然已经描述了中枢神经系统的其他神经系统表现 [ 5，例如头晕，但我们必须谨慎地将这些症状归因于病毒的直接神经毒性作用，而不是感染环境中的全身反应。

Covid-19 全球流行病的新形势对从科学到经济的各种学科提出了许多挑战。神经科医生不应忽视这种新型冠状病毒提出的问题，我们必须准备好回答这些问题。这就是为什么现在，比以往任何时候，甘道夫曾经（几乎）说过的话仍然有效：“神经学家从不迟到，也不早，他会在他想要的时候准确地到达。”