Rangon Claire-Marie, Krantic Slavica, Moyse Emmanuel, Fougère Bertrand
Pain and Neuromodulation Unit, Division of Neurosurgery, Hôpital Fondation Ophtalmologique A. De Rothschild, Paris, France.
Sorbonne Université, St. Antoine Research Center (CRSA), Inserm UMRS-938, Hopital St-Antoine, Paris, France.
J Alzheimers Dis Rep. 2020 Dec 28;4(1):537-551. doi: 10.3233/ADR-200273.
Coronavirus Disease 2019 (COVID-19) pandemic-triggered mortality is significantly higher in older than in younger populations worldwide. Alzheimer's disease (AD) is related to aging and was recently reported to be among the major risk factors for COVID-19 mortality in older people. The symptomatology of COVID-19 indicates that lethal outcomes of infection rely on neurogenic mechanisms. The present review compiles the available knowledge pointing to the convergence of COVID-19 complications with the mechanisms of autonomic dysfunctions in AD and aging. The severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) is prone to neuroinvasion from the lung along the vagus nerve up to the brainstem autonomic nervous centers involved in the coupling of cardiovascular and respiratory rhythms. The brainstem autonomic network allows SARS-CoV-2 to trigger a neurogenic switch to hypertension and hypoventilation, which may act in synergy with aging- and AD-induced dysautonomias, along with an inflammatory "storm". The lethal outcomes of COVID-19, like in AD and unhealthy aging, likely rely on a critical hypoactivity of the efferent vagus nerve cholinergic pathway, which is involved in lowering cardiovascular pressure and systemic inflammation tone. We further discuss the emerging evidence supporting the use of 1) the non-invasive stimulation of vagus nerve as an additional therapeutic approach for severe COVID-19, and 2) the demonstrated vagal tone index, i.e., heart rate variability, via smartphone-based applications as a non-serological low-cost diagnostic of COVID-19. These two well-known medical approaches are already available and now deserve large-scale testing on human cohorts in the context of both AD and COVID-19.
2019年冠状病毒病（COVID-19）大流行引发的死亡率在全球老年人群中显著高于年轻人群。阿尔茨海默病（AD）与衰老相关，最近有报道称其是老年人COVID-19死亡的主要风险因素之一。COVID-19的症状表明，感染的致命后果依赖于神经源性机制。本综述汇集了现有知识，指出COVID-19并发症与AD及衰老中自主神经功能障碍机制的趋同之处。严重急性呼吸综合征冠状病毒2（SARS-CoV-2）易于从肺部沿迷走神经侵入大脑，直至参与心血管和呼吸节律耦合的脑干自主神经中枢。脑干自主神经网络使SARS-CoV-2能够触发向高血压和通气不足的神经源性转变，这可能与衰老和AD引起的自主神经功能障碍协同作用，同时伴有炎症“风暴”。COVID-19的致命后果，如同在AD和不健康衰老中一样，可能依赖于传出迷走神经胆碱能通路的严重活动减退，该通路参与降低心血管压力和全身炎症水平。我们进一步讨论了新出现的证据，这些证据支持将以下两种方法用于：1）将迷走神经的非侵入性刺激作为重症COVID-19的一种额外治疗方法；2）通过基于智能手机的应用程序来显示迷走神经张力指数，即心率变异性，作为COVID-19非血清学低成本诊断方法。这两种广为人知的医学方法已经存在，现在值得在AD和COVID-19的背景下对人类队列进行大规模测试。
