Sanino Giulia, Bosco Martino, Terrazzano Giuseppe
Farmacia Municipale 2, Azienda Sanitaria Locale (ASL) CN1, Fossano, Italy.
Anatomia Patologica, Hospital "Michele e Pietro Ferrero", Verduno, Italy.
Front Physiol. 2020 Dec 22;11:616552. doi: 10.3389/fphys.2020.616552. eCollection 2020.
SARS-CoV2 infection not only causes abnormal severe pneumonia but also induces other relevant pathophysiological effects on several tissues and organs. In this regard, the clinical complications observed in COVID-19 include acute coronary syndrome, pulmonary thromboembolism, myocarditis and, in the severe cases, the occurrence of disseminated intravascular coagulation. Literature on COVID-19 highlighted the central role of the Renin Angiotensin Aldosterone System in the determinism of SARS-CoV2 cellular internalization in the target tissues. Lung degeneration and respiratory distress appear to be dependent on the perturbance of physiological mechanisms, such as the uncontrolled release of pro-inflammatory cytokines, a dysregulation of the fibrinolytic coagulative cascade and the hyperactivation of immune effector cells. In this mini review, we address the physiology of Midkine, a growth factor able to bind heparin, and its pathophysiological potential role in COVID-19 determinism. Midkine increases in many inflammatory and autoimmune conditions and correlates with several dysfunctional immune-inflammatory responses that appear to show similarities with the pathophysiological elicited by SARS-CoV2. Midkine, together with its receptor, could facilitate the virus entry, fostering its accumulation and increasing its affinity with Ace2 receptor. We also focus on Netosis, a particular mechanism of pathogen clearance exerted by neutrophils, which under certain pathological condition becomes dysfunctional and can cause tissue damage. Moreover, we highlight the mechanism of autophagy that the new coronavirus could try to escape in order to replicate itself, as well as on pulmonary fibrosis induced by hypoxia and on the release of cytokines and mediators of inflammation, correlating the interplay between Midkine and SARS-CoV2.
严重急性呼吸综合征冠状病毒2（SARS-CoV2）感染不仅会导致异常严重的肺炎，还会对多个组织和器官产生其他相关的病理生理影响。在这方面，新型冠状病毒肺炎（COVID-19）中观察到的临床并发症包括急性冠状动脉综合征、肺血栓栓塞、心肌炎，在严重情况下还会发生弥散性血管内凝血。关于COVID-19的文献强调了肾素血管紧张素醛固酮系统在SARS-CoV2在靶组织细胞内化过程中的核心作用。肺退变和呼吸窘迫似乎取决于生理机制的紊乱，如促炎细胞因子的失控释放、纤维蛋白溶解凝血级联反应的失调以及免疫效应细胞的过度激活。在这篇小型综述中，我们探讨了中期因子（Midkine）的生理学，它是一种能够结合肝素的生长因子，以及它在COVID-19发病机制中的病理生理潜在作用。中期因子在许多炎症和自身免疫性疾病中升高，并与几种功能失调的免疫炎症反应相关，这些反应似乎与SARS-CoV2引发的病理生理反应相似。中期因子与其受体一起，可以促进病毒进入，促进其积累并增加其与Ace2受体的亲和力。我们还关注了网织红细胞死亡，这是中性粒细胞发挥的一种特殊病原体清除机制，在某些病理条件下会功能失调并导致组织损伤。此外，我们强调了新型冠状病毒为了自我复制可能试图逃避的自噬机制，以及缺氧诱导的肺纤维化和炎症细胞因子及介质的释放，阐述了中期因子与SARS-CoV2之间的相互作用。
