Khan Aiza, Sergi Consolato
Department of Laboratory Medicine and Pathology, University of Albert Hospital, Edmonton, AB, Canada.
Department of Pediatrics, Stollery Children's Hospital, University of Alberta Hospital, Edmonton, AB, Canada.
Front Neurol. 2020 Sep 25;11:562913. doi: 10.3389/fneur.2020.562913. eCollection 2020.
The recent pandemic of coronavirus infectious illness 2019 (COVID19) triggered by SARS-CoV-2 has rapidly spread around the globe, generating in severe events an acute, highly lethal pneumonia and death. In the past two hitherto similar CoVs, the severe acute respiratory syndrome CoV (SARS-CoV-1) and Middle East respiratory syndrome CoV (MERS-CoV) also gained universal attention as they produced clinical symptoms similar to those of SARS-CoV-2 utilizing angiotensin-converting enzyme 2 (ACE2) receptor and dipeptidyl peptidase 4 (DPP4) to go into the cells. COVID-19 may also present with overtly neurological symptoms. The proper understanding of the expression and dissemination of ACE2 in central and peripheral nerve systems is crucial to understand better the neurological morbidity caused by COVID-19. Using the STRING bioinformatic tool and references through text mining tools associated to Coronaviruses, we identified SAMHD1 as the probable link to neurological symptoms. Paralleled to the response to influenza A virus and, specifically, respiratory syncytial virus, SARS-CoV-2 evokes a response that needs robust induction of a subclass of cytokines, including the Type I and, obviously, Type III interferons as well as a few chemokines. We correlate ACE2 to the pathogenesis and neurologic complications of COVID-19 and found that SAMHD1 links to NF-κB pathway. No correlation was found with other molecules associated with Coronavirus infection, including ADAR, BST2, IRF3, IFITM3, ISG15, MX1, MX2, RNASEL, RSAD2, and VPRBP. We suggest that SAMHD1 is the molecule that may be behind the mechanisms of the neurological complications associated with COVID-19.
由严重急性呼吸综合征冠状病毒2（SARS-CoV-2）引发的2019年冠状病毒感染疾病（COVID-19）大流行已在全球迅速蔓延，在严重情况下会引发急性、高致死性肺炎并导致死亡。在过去两种此前类似的冠状病毒，即严重急性呼吸综合征冠状病毒（SARS-CoV-1）和中东呼吸综合征冠状病毒（MERS-CoV）中，它们也引起了广泛关注，因为它们利用血管紧张素转换酶2（ACE2）受体和二肽基肽酶4（DPP4）进入细胞，产生了与SARS-CoV-2相似的临床症状。COVID-19也可能出现明显的神经症状。正确理解ACE2在中枢和外周神经系统中的表达和传播对于更好地理解COVID-19引起的神经病变至关重要。使用STRING生物信息工具并通过与冠状病毒相关的文本挖掘工具参考文献，我们确定SAMHD1可能是与神经症状相关的联系。与对甲型流感病毒，特别是呼吸道合胞病毒的反应相似，SARS-CoV-2引发的反应需要强力诱导一类细胞因子，包括I型以及明显的III型干扰素以及一些趋化因子。我们将ACE2与COVID-19的发病机制和神经并发症相关联，发现SAMHD1与NF-κB途径相关。未发现与其他与冠状病毒感染相关的分子存在相关性，包括ADAR、BST2、IRF3、IFITM3、ISG15、MX1、MX2、RNASEL、RSAD2和VPRBP。我们认为SAMHD1可能是COVID-19相关神经并发症机制背后的分子。
