The COVID-19 pandemic caused by the coronavirus (SARS-CoV-2) has taken the world by surprise into a major crisis of overwhelming morbidity and mortality. This highly infectious disease is associated with respiratory failure unusual in other coronavirus infections. Mounting evidence link the accelerated progression of the disease in COVID-19 patients to the hyper-inflammatory state termed as the “cytokine storm” involving major systemic perturbations. These include iron dysregulation manifested as hyperferritinemia associated with disease severity. Iron dysregulation induces reactive oxygen species (ROS) production and promotes oxidative stress. The mitochondria are the hub of cellular oxidative homeostasis. In addition, the mitochondria may circulate “cell-free” in non-nucleated platelets, in extracellular vesicles and mitochondrial DNA is found in the extracellular space. The heightened inflammatory/oxidative state may lead to mitochondrial dysfunction leading to platelet damage and apoptosis. The interaction of dysfunctional platelets with coagulation cascades aggravates clotting events and thrombus formation. Furthermore, mitochondrial oxidative stress may contribute to microbiota dysbiosis, altering coagulation pathways and fueling the inflammatory/oxidative response leading to the vicious cycle of events. Here, we discuss various cellular and systemic incidents caused by SARS-CoV-2 that may critically impact intra and extracellular mitochondrial function, and contribute to the progression and severity of the disease. It is crucial to understand how these key modulators impact COVID-19 pathogenesis in the quest to identify novel therapeutic targets that may reduce fatal outcomes of the disease.

中文翻译：

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COVID-19 发病机制中的线粒体和微生物群功能障碍

由冠状病毒 (SARS-CoV-2) 引起的 COVID-19 大流行让世界意外地陷入了一场发病率和死亡率极高的重大危机。这种高度传染性疾病与其他冠状病毒感染中不常见的呼吸衰竭有关。越来越多的证据将 COVID-19 患者疾病的加速进展与称为“细胞因子风暴”的过度炎症状态联系起来，涉及主要的全身扰动。这些包括表现为与疾病严重程度相关的高铁蛋白血症的铁失调。铁失调会诱导活性氧 (ROS) 的产生并促进氧化应激。线粒体是细胞氧化稳态的枢纽。此外，线粒体可能在无核血小板中“无细胞”循环，在细胞外囊泡中，线粒体 DNA 存在于细胞外空间中。炎症/氧化状态升高可能导致线粒体功能障碍，从而导致血小板损伤和细胞凋亡。功能失调的血小板与凝血级联反应的相互作用加剧了凝血事件和血栓形成。此外，线粒体氧化应激可能导致微生物群失调，改变凝血途径并加剧炎症/氧化反应，从而导致事件的恶性循环。在这里，我们讨论了由 SARS-CoV-2 引起的各种细胞和全身事件，这些事件可能严重影响细胞内外线粒体功能，并导致疾病的进展和严重程度。