Department of Biology, Faculty of Sciences 2, Campus Fanar, Lebanese University, Jdeidet El-Matn 1202, Lebanon.
Department of Biology, Faculty of Sciences 3, Campus Michel Slayman Ras Maska, Lebanese University, Tripoli 1352, Lebanon.
Molecules. 2021 Nov 17;26(22):6945. doi: 10.3390/molecules26226945.
The novel severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), the causative agent of coronavirus disease 2019 (COVID-19), was first identified in Eastern Asia (Wuhan, China) in December 2019. The virus then spread to Europe and across all continents where it has led to higher mortality and morbidity, and was declared as a pandemic by the World Health Organization (WHO) in March 2020. Recently, different vaccines have been produced and seem to be more or less effective in protecting from COVID-19. The renin-angiotensin system (RAS), an essential enzymatic cascade involved in maintaining blood pressure and electrolyte balance, is involved in the pathogenicity of COVID-19, since the angiotensin-converting enzyme II (ACE2) acts as the cellular receptor for SARS-CoV-2 in many human tissues and organs. In fact, the viral entrance promotes a downregulation of ACE2 followed by RAS balance dysregulation and an overactivation of the angiotensin II (Ang II)-angiotensin II type I receptor (AT1R) axis, which is characterized by a strong vasoconstriction and the induction of the profibrotic, proapoptotic and proinflammatory signalizations in the lungs and other organs. This mechanism features a massive cytokine storm, hypercoagulation, an acute respiratory distress syndrome (ARDS) and subsequent multiple organ damage. While all individuals are vulnerable to SARS-CoV-2, the disease outcome and severity differ among people and countries and depend on a dual interaction between the virus and the affected host. Many studies have already pointed out the importance of host genetic polymorphisms (especially in the RAS) as well as other related factors such age, gender, lifestyle and habits and underlying pathologies or comorbidities (diabetes and cardiovascular diseases) that could render individuals at higher risk of infection and pathogenicity. In this review, we explore the correlation between all these risk factors as well as how and why they could account for severe post-COVID-19 complications.
新型严重急性呼吸综合征冠状病毒 2（SARS-CoV-2），即导致 2019 年冠状病毒病（COVID-19）的病原体，于 2019 年 12 月在中国东部（武汉）首次被鉴定出来。该病毒随后传播到欧洲，并蔓延到各大洲，导致更高的死亡率和发病率，并于 2020 年 3 月被世界卫生组织（WHO）宣布为大流行。最近，已经生产出了不同的疫苗，它们在预防 COVID-19 方面或多或少都有一定的效果。肾素-血管紧张素系统（RAS）是一种参与维持血压和电解质平衡的重要酶级联反应系统，它与 COVID-19 的发病机制有关，因为血管紧张素转换酶 2（ACE2）在许多人体组织和器官中充当 SARS-CoV-2 的细胞受体。事实上，病毒进入会导致 ACE2 的下调，继而导致 RAS 平衡失调和血管紧张素 II（Ang II）-血管紧张素 II 型受体（AT1R）轴的过度激活，其特征是强烈的血管收缩以及在肺部和其他器官中诱导成纤维增生、促凋亡和促炎信号。这种机制导致大量细胞因子风暴、高凝状态、急性呼吸窘迫综合征（ARDS）和随后的多器官损伤。虽然所有个体都容易受到 SARS-CoV-2 的影响，但疾病的结局和严重程度在人与人之间和国家之间存在差异，这取决于病毒和受影响宿主之间的双重相互作用。许多研究已经指出了宿主遗传多态性（尤其是在 RAS 中）以及其他相关因素（如年龄、性别、生活方式和习惯以及潜在的病理或合并症（糖尿病和心血管疾病））的重要性，这些因素可能使个体面临更高的感染和发病风险。在这篇综述中，我们探讨了所有这些危险因素之间的相关性，以及它们如何以及为什么可以解释 COVID-19 后的严重并发症。
