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2020年4月15日，心血管顶级杂志Circulation在线发表了武汉大学李红良教授与加拿大渥太华大学心脏中心的PeterP. Liu教授合作的题为“The Science underlying COVID-19: Implications for the Cardiovascular System”的深度综述文章。该文章围绕COVID-19对心血管系统的影响，从临床和基础的角度对COVID-19进行了系统地梳理和阐述。现有的流行病学资料表明，COVID-19患者中合并心血管疾病的比例较高，而该类患者的死亡率也显著上升。据报道，合并心血管疾病的COVID-19患者死亡率为10.5%，合并高血压患者的死亡率为6.0%，远远高于没有合并症的患者（0.9%）。细胞表面受体ACE2和丝氨酸蛋白酶TMPRSS2是SARS-CoV-2入侵宿主细胞的关键蛋白。ACE2和TMPRSS2共同表达于肺脏，心脏，胃肠道，肝脏，肾脏，神经元以及免疫细胞。研究表明，在糖尿病，高血压以及心衰患者中ACE2的表达量和活性显著增高。另外，ACE2的表达水平具有明显的性别差异，即男性患者的死亡率高于女性。在心衰患者中，男性外周循环的ACE2明显高于女性。ACE2能够将AngII水解成Ang 1-7，后者作用于Mas受体，发挥拮抗Ang II/AT1R的效应，如降低血压，舒张血管，抑制炎症和氧化应激等。SARS-CoV-2的感染引起ACE2的降低，使RAS系统的平衡向AngII/AT1R偏移，促进组织损伤。尽管目前并没有确切的证据评估，RAS系统抑制剂，如ACEIs/ARBs类药物对COVID-19患者的利弊，多数医疗组织推荐具有ACEIs/ARBs用药指征的患者继续使用该类药物。事实上，本团队的大样本临床研究证实，对于有用药指征的COVID-19患者（如高血压），ACEIs/ARBs的使用益处大于风险。 
血管平滑肌细胞上表达ACE2和TMPRSS2，也是新冠病毒的潜在感染靶点。COVID-19患者的病理分析结果发现，在肺脏和其它受累组织中均存在微血管炎症和微血栓形成。此外，巨噬细胞的活化和内皮细胞的功能失调也对微血管炎症和微血栓形成起着推波助澜的作用。微血管炎症和微血栓形成能够加重患者的缺氧状态，促进组织损伤，严重影响患者预后。针对合并微血管炎症和微血栓形成的患者，如实验室检查发现IL-6和D-二聚体显著升高，应尽早考虑抗炎和抗凝药物的治疗，改善患者预后。8-28%的COVID-19患者伴有肌钙蛋白的升高，提示心肌损伤的发生。合并心肌损伤的COVID-19患者，死亡率显著上升，表明心肌损伤和患者的预后密切相关。部分患者可能伴有心脏的直接受累，包括心肌病、心肌炎或心力衰竭，影响患者的总体预后，早期识别和干预能够显著改善患者的临床结局。疑似急性心肌炎和心肌病的患者，心脏磁共振成像检查具有一定的价值。对于合并心衰的患者，应该考虑应用包括RAS抑制剂在内的相关治疗药物。心律失常是COVID-19患者的另一种常见并发症。研究表明，ICU收治的COVID-19患者中，房颤发生率高达50%，这些患者也伴有室性心律失常和心脏骤停。COVID-19患者心律失常的高发生率可部分归因于患者在病毒感染时的代谢紊乱、缺氧、神经激素及炎症应激，也可能与潜在的心肌炎和治疗药物的副作用有关。DOI:10.1161/CIRCULATIONAHA.120.047549 
Corona Virus Disease 2019 (COVID-19) pandemic has impacted health and economy worldwide on an unprecedented scale. Patients have diverse clinical outcomes, but those with pre-existing cardiovascular (CV) disease, hypertension, and related conditions incur disproportionately worse outcome. The high infectivity of the SARS-CoV-2 virus is in part related to new mutations in the receptor binding domain, and acquisition of a furin cleavage site in the S spike protein. The continued viral shedding in the asymptomatic and pre-symptomatic individuals enhances its community transmission. The virus uses the ACE2 receptor for internalization, aided by TMPRSS2 protease. The tissue localization of the receptors correlates with COVDI-19 presenting symptoms and organ dysfunction. Virus-induced ACE2 down regulation may attenuate its function, diminish its anti-inflammatory role, and heightened angiotensin II effects in the predisposed patients. Lymphopenia occurs early and is prognostic, potentially associated with reduction of the CD4 and some CD8 T cells. This leads to imbalance of the innate/acquired immune response, delayed viral clearance, and hyper stimulated macrophages and neutrophils. Appropriate type I interferon pathway activation is critical for virus attenuation, and balanced immune response. Persistent immune activation in predisposed patients, such as the elderly and those with CV risk, can lead to hemophagocytosis like syndrome, with uncontrolled amplification of cytokine production, leading to multi-organ failure and death. In addition to the airways and lungs, the cardiovascular system is often involved in COVID-19 early, reflected in the release of highly sensitive troponin and natriuretic peptides, which are all extremely prognostic, particularly in those showing continued rise, along with cytokines such as IL-6. Inflammation in the vascular system can result in diffuse microangiopathy with thrombosis. Inflammation in the myocardium can result in myocarditis, heart failure, cardiac arrhythmias, acute coronary syndrome, rapid deterioration and sudden death. Aggressive support based on early prognostic indicators with expectant management can potentially improve recovery. Appropriate treatment for heart failure, arrhythmias, acute coronary syndrome and thrombosis remain important. Specific evidence based treatment strategies for COVID-19 will emerge with ongoing global collaboration on multiple approaches being evaluated. To protect the wider population, antibody testing and effective vaccine will be needed to make COVID-19 history.机构简介武汉大学动物实验中心（简称中心）和武汉大学ABSL-Ⅲ实验室（生物安全三级动物实验室，简称A3实验室）源于1958年成立的湖北医学院动物室，迄今已走过甲子芳华。1994年，湖北医科大学动物实验中心成立，后于2000年并入武汉大学，实验动物中心由此划归武汉大学医学院；2003年，武汉大学动物实验中心与武汉大学ABSL-Ⅲ实验室由国家发展与改革委员会、教育部、武汉大学共同投资建设而成；2012年，武汉大学模式动物协同创新中心成立，继而成立武汉大学模式动物研究所，和中心/A3实验室同为武汉大学二级单位，实行一套班子，三块牌子，是面向校内外开放的公共服务平台和科研机构。编辑、审核：苏果 荐稿：Yin Yuan 素材来源：武汉大学动物实验中心（简称中心）、武汉大学ABSL-Ⅲ实验室、期刊Circulation 网址链接：https://www./doi/abs/10.1161/CIRCULATIONAHA.120.047549 版权声明：文章转摘只为学术传播，如涉及侵权问题，请联系我们，我们将及时修改或删除。 |
