Department of Radiology, Azienda Ospedaliero Universitaria (AOU), di Cagliari - Polo di Monserrato, Cagliari, Italy.
Eur Rev Med Pharmacol Sci. 2020 Dec;24(23):12609-12622. doi: 10.26355/eurrev_202012_24058.
In human pathology, SARS-CoV-2 utilizes multiple molecular pathways to determine structural and biochemical changes within the different organs and cell types. The clinical picture of patients with COVID-19 is characterized by a very large spectrum. The reason for this variability has not been clarified yet, causing the inability to make a prognosis on the evolution of the disease.
PubMed search was performed focusing on the role of ACE 2 receptors in allowing the viral entry into cells, the role of ACE 2 downregulation in triggering the tissue pathology or in accelerating previous disease states, the role of increased levels of Angiotensin II in determining endothelial dysfunction and the enhanced vascular permeability, the role of the dysregulation of the renin angiotensin system in COVID-19 and the role of cytokine storm.
The pathological changes induced by SARS-CoV-2 infection in the different organs, the correlations between the single cell types targeted by the virus in the different human organs and the clinical consequences, COVID-19 chronic pathologies in liver fibrosis, cardiac fibrosis and atrial arrhythmias, glomerulosclerosis and pulmonary fibrosis, due to the systemic fibroblast activation induced by angiotensin II are discussed.
The main pathways involved showed different pathological changes in multiple tissues and the different clinical presentations. Even if ACE2 is the main receptor of SARS-CoV-2 and the main entry point into cells for the virus, ACE2 expression does not always explain the observed marked inter-individual variability in clinical presentation and outcome, evidencing the complexity of this disorder. The proper interpretation of the growing data available might allow to better classifying COVID-19 in human pathology.
在人类病理学中，SARS-CoV-2 通过多种分子途径来确定不同器官和细胞类型内的结构和生化变化。COVID-19 患者的临床表现具有很大的谱。其原因尚未阐明，这导致无法对疾病的演变做出预后。
在 PubMed 上进行了搜索，重点关注 ACE 2 受体在允许病毒进入细胞中的作用、ACE 2 下调在触发组织病理学或加速先前疾病状态中的作用、血管紧张素 II 水平升高在确定内皮功能障碍和增强血管通透性中的作用、肾素-血管紧张素系统失调在 COVID-19 中的作用以及细胞因子风暴的作用。
讨论了 SARS-CoV-2 感染在不同器官中引起的病理变化、病毒在不同人体器官中靶向的单个细胞类型之间的相关性以及临床后果、肝纤维化、心脏纤维化和心房心律失常、肾小球硬化和肺纤维化中的 COVID-19 慢性病理、由于血管紧张素 II 引起的全身成纤维细胞激活。
所涉及的主要途径在多种组织中显示出不同的病理变化和不同的临床表现。即使 ACE2 是 SARS-CoV-2 的主要受体和病毒进入细胞的主要切入点，ACE2 的表达并不总是能解释观察到的临床表型和结果中的明显个体间变异性，这表明该疾病的复杂性。对现有数据的正确解释可能有助于更好地将 COVID-19 分类为人类病理学。
