Jalodia Richa, Antoine Danielle, Braniff Regina Gonzalez, Dutta Rajib Kumar, Ramakrishnan Sundaram, Roy Sabita
Department of Surgery, University of Miami Miller School of Medicine, Miami, FL, United States.
Front Neurol. 2022 May 23;13:884216. doi: 10.3389/fneur.2022.884216. eCollection 2022.
Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is an imminent threat to human health and public safety. ACE2 and transmembrane serine protease 2 proteins on host cells provide the viral entry point to SARS-CoV-2. Although SARS-CoV-2 mainly infects the respiratory system, there have been reports of viral neurotropism and central nervous system injury as indicated by plasma biomarkers, including neurofilament light chain protein and glial fibrillary acidic protein. Even with a small proportion of infections leading to neurological manifestation, the overall number remains high. Common neurological manifestations of SARS-CoV-2 infection include anosmia, ageusia, encephalopathy, and stroke, which are not restricted to only the most severe infection cases. Opioids and opioid antagonists bind to the ACE2 receptor and thereby have been hypothesized to have therapeutic potential in treating COVID-19. However, in the case of other neurotropic viral infections such as human immunodeficiency virus (HIV), opioid use has been established to exacerbate HIV-mediated central nervous system pathogenesis. An analysis of electronic health record data from more than 73 million patients shows that people with Substance Use Disorders are at higher risk of contracting COVID-19 and suffer worse consequences then non-users. Our and unpublished studies show that morphine treatment causes increased expression of ACE2 in murine lung and brain tissue as early as 24 h post treatment. At the same time, we also observed morphine and lipopolysaccharides treatment lead to a synergistic increase in ACE2 expression in the microglial cell line, SIM-A9. This data suggests that opioid treatment may potentially increase neurotropism of SARS-CoV-2 infection. We have previously shown that opioids induce gut microbial dysbiosis. Similarly, gut microbiome alterations have been reported with SARS-CoV-2 infection and may play a role in predicting COVID-19 disease severity. However, there are no studies thus far linking opioid-mediated dysbiosis with the severity of neuron-specific COVID-19 infection.
严重急性呼吸综合征冠状病毒2（SARS-CoV-2）对人类健康和公共安全构成迫在眉睫的威胁。宿主细胞上的血管紧张素转换酶2（ACE2）和跨膜丝氨酸蛋白酶2蛋白为SARS-CoV-2提供了病毒进入点。虽然SARS-CoV-2主要感染呼吸系统，但已有报道称存在病毒嗜神经性和中枢神经系统损伤，血浆生物标志物如神经丝轻链蛋白和胶质纤维酸性蛋白表明了这一点。即使只有一小部分感染会导致神经表现，但总体数量仍然很高。SARS-CoV-2感染的常见神经表现包括嗅觉丧失、味觉丧失、脑病和中风，这些并不局限于最严重的感染病例。阿片类药物和阿片类拮抗剂与ACE2受体结合，因此被推测在治疗COVID-19方面具有治疗潜力。然而，在其他嗜神经性病毒感染如人类免疫缺陷病毒（HIV）的情况下，已证实使用阿片类药物会加剧HIV介导的中枢神经系统发病机制。对超过7300万患者的电子健康记录数据进行的分析表明，患有物质使用障碍的人感染COVID-19的风险更高，且比未使用者的后果更严重。我们和未发表的研究表明，吗啡治疗早在治疗后24小时就会导致小鼠肺和脑组织中ACE2表达增加。同时，我们还观察到吗啡和脂多糖治疗会导致小胶质细胞系SIM-A9中ACE2表达协同增加。这些数据表明，阿片类药物治疗可能会增加SARS-CoV-2感染的嗜神经性。我们之前已经表明，阿片类药物会诱导肠道微生物群失调。同样，已有报道称SARS-CoV-2感染会导致肠道微生物群改变，并可能在预测COVID-19疾病严重程度方面发挥作用。然而，迄今为止，尚无研究将阿片类药物介导的失调与神经元特异性COVID-19感染的严重程度联系起来。
