Dyspneic and non-dyspneic (silent) hypoxemia in COVID-19: Possible neurological mechanism
Dyspneic and non-dyspneic (silent) hypoxemia in COVID-19: Possible neurological mechanism
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DOI：
10.1016/j.clineuro.2020.106217
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发表时间：
2020-11-01
影响因子：
1.9
通讯作者：
Sharifi, Akbar
中科院分区：
文献类型：
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作者：
Nouri-Vaskeh, Masoud;Sharifi, Ali;Sharifi, Akbar
SARS-CoV-2主要通过粘附于血管紧张素转换酶2（ACE-2）而侵入呼吸道上皮细胞，因此，感染的患者可发生轻度至重度的炎症反应和急性肺损伤。由炎性细胞因子刺激肺机械化学感受器、外周和中枢化学感受器产生的传入冲动被传导至脑干。这些输入信号的整合和处理发生在中枢神经系统内，特别是在边缘系统和感觉运动皮层，重要的是O-2、CO2和血液pH之间存在反馈调节。尽管COVID-19的低氧血症强度很大，但呼吸困难感觉的强度与某些患者的低氧血症程度不相称（无症状低氧血症）。我们假设SARS-CoV-2可能导致皮质边缘网络中的神经元损伤，随后改变呼吸困难的感知和呼吸控制。SARS-CoV-2神经元感染可能会改变许多内源性神经肽或神经递质的分泌，这些神经肽或神经递质分布在神经系统的大区域，产生细胞和感知效应。SARS-CoV-2主要通过直接（神经和血液途径）和间接途径进入中枢神经系统。我们推测SARS-CoV-2感染诱导神经元细胞损伤，并可能改变分布在神经系统大面积的内源性神经肽或神经递质的平衡，产生细胞和感知效应。因此，SARS-CoV-2相关的神经元损伤可能会影响呼吸的控制，通过相互作用在呼吸调节。这将为COVID-19诱导缺氧的中枢机制的进展开辟可能的研究路线。未来的研究需要证实或反驳这样的假设。
SARS-CoV-2 mainly invades respiratory epithelial cells by adhesion to angiotensin-converting enzyme 2 (ACE-2) and thus, infected patients may develop mild to severe inflammatory responses and acute lung injury. Afferent impulses that result from the stimulation of pulmonary mechano-chemoreceptors, peripheral and central chemoreceptors by inflammatory cytokines are conducted to the brainstem. Integration and processing of these input signals occur within the central nervous system, especially in the limbic system and sensorimotor cortex, and importantly feedback regulation exists between O-2, CO2, and blood pH. Despite the intensity of hypoxemia in COVID-19, the intensity of dyspnea sensation is inappropriate to the degree of hypoxemia in some patients (silent hypoxemia). We hypothesize that SARS-CoV-2 may cause neuronal damage in the corticolimbic network and subsequently alter the perception of dyspnea and the control of respiration. SARS-CoV-2 neuronal infection may change the secretion of numerous endogenous neuropeptides or neurotransmitters that distribute through large areas of the nervous system to produce cellular and perceptual effects. SARS-CoV-2 mainly enter to CNS via direct (neuronal and hematologic route) and indirect route. We theorize that SARS-CoV-2 infection-induced neuronal cell damage and may change the balance of endogenous neuropeptides or neurotransmitters that distribute through large areas of the nervous system to produce cellular and perceptual effects. Thus, SARS-CoV-2-associated neuronal damage may influence the control of respiration by interacting in neummodulation. This would open up possible lines of study for the progress in the central mechanism of COVID-19-induced hypoxia. Future research is desirable to confirm or disprove such a hypothesis.