One of the most frequent symptoms of COVID-19 is the loss of smell and taste. Based on the lack of expression of the virus entry proteins in olfactory receptor neurons, it was originally assumed that the new coronavirus (severe acute respiratory syndrome coronavirus 2, SARS-CoV-2) does not infect olfactory neurons. Recent studies have reported otherwise, opening the possibility that the virus can directly infect the brain by traveling along the olfactory nerve. Multiple animal models have been employed to assess mechanisms and routes of brain infection of SARS-CoV-2, often with conflicting results. We here review the current evidence for an olfactory route to brain infection and conclude that the case for infection of olfactory neurons is weak, based on animal and human studies. Consistent brain infection after SARS-CoV-2 inoculation in mouse models is only seen when the virus entry proteins are expressed abnormally, and the timeline and progression of rare neuro-invasion in these and in other animal models points to alternative routes to the brain, other than along the olfactory projections. COVID-19 patients can be assured that loss of smell does not necessarily mean that the SARS-CoV-2 virus has gained access to and has infected their brains.

COVID-19 最常见的症状之一是嗅觉和味觉丧失。基于嗅觉受体神经元中病毒进入蛋白的缺乏表达，最初假设新型冠状病毒（严重急性呼吸综合征冠状病毒2，SARS-CoV-2）不会感染嗅觉神经元。最近的研究却报告了相反的情况，这开启了病毒可以通过嗅觉神经传播直接感染大脑的可能性。多种动物模型已被用来评估 SARS-CoV-2 脑部感染的机制和途径，但结果往往相互矛盾。我们在这里回顾了嗅觉途径导致脑部感染的现有证据，并根据动物和人类研究得出结论，嗅觉神经元感染的证据薄弱。仅当病毒进入蛋白表达异常时，小鼠模型中接种 SARS-CoV-2 后才会出现持续的脑部感染，这些和其他动物模型中罕见神经侵袭的时间线和进展表明了通往大脑的替代途径，除了沿着嗅觉投射之外。COVID-19 患者可以放心，嗅觉丧失并不一定意味着 SARS-CoV-2 病毒已经进入并感染了他们的大脑。