Gouda Ahmed S, Adbelruhman Fatima G, Elbendary Reham N, Alharbi Fadiyah Ahmed, Alhamrani Sultan Qalit, Mégarbane Bruno
National Egyptian Center for Toxicological Researches, Faculty of Medicine, Cairo University, Cairo, Egypt.
Poison Control and Forensic Chemistry Center, Northern Borders, Ministry of Health, Saudi Arabia.
Saudi J Biol Sci. 2021 Jun;28(6):3540-3547. doi: 10.1016/j.sjbs.2021.03.027. Epub 2021 Mar 16.
Hypozincemia is prevalent in severe acute respiratory syndrome coronavirus-2 (SARS-COV-2)-infected patients and has been considered as a risk factor in severe coronavirus disease-2019 (COVID-19). Whereas zinc might affect SARS-COV-2 replication and cell entry, the link between zinc deficiency and COVID-19 severity could also be attributed to the effects of COVID-19 on the body metabolism and immune response. Zinc deficiency is more prevalent in the elderly and patients with underlying chronic diseases, with established deleterious consequences such as the increased risk of respiratory infection. We reviewed the expected effects of zinc deficiency on COVID-19-related pathophysiological mechanisms focusing on both the renin-angiotensin and kinin-kallikrein systems. Mechanisms and effects were extrapolated from the available scientific literature. Zinc deficiency alters angiotensin-converting enzyme-2 (ACE2) function, leading to the accumulation of angiotensin II, des-Arg9-bradykinin and Lys-des-Arg9-bradykinin, which results in an exaggerated pro-inflammatory response, vasoconstriction and pro-thrombotic effects. Additionally, zinc deficiency blocks the activation of the plasma contact system, a protease cascade initiated by factor VII activation. Suggested mechanisms include the inhibition of Factor XII activation and limitation of high-molecular-weight kininogen, prekallikrein and Factor XII to bind to endothelial cells. The subsequent accumulation of Factor XII and deficiency in bradykinin are responsible for increased production of inflammatory mediators and marked hypercoagulability, as typically observed in COVID-19 patients. To conclude, zinc deficiency may affect both the renin-angiotensin and kinin-kallikrein systems, leading to the exaggerated inflammatory manifestations characteristic of severe COVID-19.
低锌血症在严重急性呼吸综合征冠状病毒2（SARS-CoV-2）感染患者中普遍存在，并被认为是2019冠状病毒病（COVID-19）严重程度的一个风险因素。虽然锌可能影响SARS-CoV-2的复制和细胞进入，但锌缺乏与COVID-19严重程度之间的联系也可能归因于COVID-19对身体代谢和免疫反应的影响。锌缺乏在老年人和患有慢性基础疾病的患者中更为普遍，会产生如呼吸道感染风险增加等既定的有害后果。我们综述了锌缺乏对与COVID-19相关的病理生理机制的预期影响，重点关注肾素-血管紧张素系统和激肽-激肽释放酶系统。相关机制和影响是从现有科学文献中推断出来的。锌缺乏会改变血管紧张素转换酶2（ACE2）的功能，导致血管紧张素II、去-精氨酸9-缓激肽和赖氨酸-去-精氨酸9-缓激肽的积累，从而引发过度的促炎反应、血管收缩和促血栓形成作用。此外，锌缺乏会阻断血浆接触系统的激活，这是一种由因子VII激活引发的蛋白酶级联反应。推测的机制包括抑制因子XII的激活以及限制高分子量激肽原、前激肽释放酶和因子XII与内皮细胞结合。随后因子XII的积累和缓激肽的缺乏导致炎症介质产生增加和明显的高凝状态，这在COVID-19患者中较为常见。总之，锌缺乏可能会影响肾素-血管紧张素系统和激肽-激肽释放酶系统，导致严重COVID-19特有的炎症表现加剧。
