COVID-19: hemoglobin, iron, and hypoxia beyond inflammation. A narrative review
COVID-19: hemoglobin, iron, and hypoxia beyond inflammation. A narrative review
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DOI：
10.4081/cp.2020.1271
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发表时间：
2020-01-01
影响因子：
2.3
通讯作者：
Corrao, Salvatore
中科院分区：
文献类型：
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作者：
Cavezzi, Attilio;Troiani, Emidio;Corrao, Salvatore
冠状病毒病 19 (COVID-19) 被认为是一种感染性炎症性疾病，主要影响肺部。最近，多器官受累以及不同的损伤途径受到关注。血红蛋白病、缺氧和细胞铁超载可能具有额外的作用。科学文献指出了两种潜在的病理生理机制：i）严重急性呼吸综合征-冠状病毒2（SARS-CoV-2）通过CD147、CD26和位于红细胞和/或血细胞前体上的其他受体与血红蛋白分子相互作用； ii) 病毒刺突蛋白的铁调素模拟作用，诱导铁转运蛋白阻断。在这篇基于转化医学的叙述性综述中，强调了以下源自血红蛋白变性和铁代谢失调的病理代谢途径：i）功能性血红蛋白引用减少； ii) 细胞/组织铁超载（高铁蛋白血症）； iii) 释放游离的有毒循环血红素； iv) 低氧血症和全身性缺氧； v) 减少一氧化氮； vi) 凝血激活； vii) 氧化应激和脂过氧化引起的铁死亡； viii) 线粒体变性和细胞凋亡。随后可能出现一些临床综合征，例如基于动脉血管收缩和肺泡毛细血管屏障改变的肺水肿、铁粒幼细胞样贫血、内皮炎、血管痉挛性肢端综合征和动静脉血栓栓塞。我们推测，在 COVID-19 中，除了经典的肺部免疫炎症观点之外，还应考虑缺氧血液疾病的发生以及铁代谢失调。提出了一种更全面的 COVID-19 诊断/治疗方法，包括旨在改善血红蛋白功能障碍、铁过度沉积和全身缺氧状态的潜在辅助干预措施。
Coronavirus disease-19 (COVID-19) has been regarded as an infective-inflammatory disease, which affects mainly lungs. More recently, a multi-organ involvement has been highlighted, with different pathways of injury. A hemoglobinopathy, hypoxia and cell iron overload might have a possible additional role. Scientific literature has pointed out two potential pathophysiological mechanisms: i) severe acute respiratory syndrome-coronavirus-2 (SARS-CoV-2) interaction with hemoglobin molecule, through CD147, CD26 and other receptors located on erythrocyte and/or blood cell precursors; ii) hepcidin-mimetic action of a viral spike protein, inducing ferroportin blockage. In this translational medicine-based narrative review, the following pathologic metabolic pathways, deriving from hemoglobin denaturation and iron metabolism dysregulation, are highlighted: i) decrease of functioning hemoglobin quote; ii) iron overload in cell/tissue (hyperferritinemia); iii) release of free toxic circulating heme; iv) hypoxemia and systemic hypoxia; v) reduction of nitric oxide; vi) coagulation activation; vii) ferroptosis with oxidative stress and lipoperoxidation; viii) mitochondrial degeneration and apoptosis. A few clinical syndromes may follow, such as pulmonary edema based on arterial vasoconstriction and altered alveolo-capillary barrier, sideroblastic-like anemia, endotheliitis, vasospastic acrosyndrome, and arterio- venous thromboembolism. We speculated that in COVID-19, beyond the classical pulmonary immune-inflammation view, the occurrence of an oxygen-deprived blood disease, with iron metabolism dysregulation, should be taken in consideration. A more comprehensive diagnostic/therapeutic approach to COVID-19 is proposed, including potential adjuvant interventions aimed at improving hemoglobin dysfunction, iron over-deposit and generalized hypoxic state.