Background

Decline in mitochondrial function occurs with aging and may increase mortality. We discuss mitochondrial contribution to Covid-19 sepsis, specifically the complex interaction of innate immune function, viral replication, hyper-inflammatory state, and HIF-α/Sirtuin pathways.

Methods

Articles from PubMed/Medline searches were reviewed using the combination of terms “SARS-CoV-2, Covid-19, sepsis, mitochondria, aging, and immunometabolism”.

Results

Evidence indicates that mitochondria in senescent cells may be dysfunctional and unable to keep up with hypermetabolic demands associated with Covid-19 sepsis. Mitochondrial proteins may serve as damage-associated molecular pattern (DAMP) activating innate immunity. Disruption in normal oxidative phosphorylation pathways contributes to elevated ROS which activates sepsis cascade through HIF-α/Sirtuin pathway. Viral–mitochondrial interaction may be necessary for replication and increased viral load. Hypoxia and hyper-inflammatory state contribute to increased mortality associated with Covid-19 sepsis.

Conclusions

Aging is associated with worse outcomes in sepsis. Modulating Sirtuin activity is emerging as therapeutic agent in sepsis. HIF-α, levels of mitochondrial DNA, and other mitochondrial DAMP molecules may also serve as useful biomarker and need to be investigated. These mechanisms should be explored specifically for Covid-19-related sepsis. Understanding newly discovered regulatory mechanisms may lead to the development of novel diagnostic and therapeutic targets.

中文翻译：

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冠状病毒 (Covid-19) 败血症：重新审视发病机制、衰老、炎症和死亡率中的线粒体功能障碍。

背景

线粒体功能会随着年龄的增长而下降，并可能增加死亡率。我们讨论了线粒体对 Covid-19 脓毒症的贡献，特别是先天免疫功能、病毒复制、高炎症状态和 HIF-α/Sirtuin 通路的复杂相互作用。

方法

使用术语“SARS-CoV-2、Covid-19、脓毒症、线粒体、衰老和免疫代谢”对来自 PubMed/Medline 搜索的文章进行了审查。

结果

有证据表明，衰老细胞中的线粒体可能功能失调，无法满足与 Covid-19 脓毒症相关的高代谢需求。线粒体蛋白可作为激活先天免疫的损伤相关分子模式 (DAMP)。正常氧化磷酸化途径的破坏导致 ROS 升高，从而通过 HIF-α/Sirtuin 途径激活脓毒症级联反应。病毒 - 线粒体相互作用可能是复制和增加病毒载量所必需的。缺氧和高炎症状态导致与 Covid-19 败血症相关的死亡率增加。

结论

衰老与败血症的更坏结果有关。调节 Sirtuin 活性正在成为脓毒症的治疗剂。HIF-α、线粒体 DNA 水平和其他线粒体 DAMP 分子也可以作为有用的生物标志物，需要进行研究。应专门针对与 Covid-19 相关的败血症探索这些机制。了解新发现的调节机制可能会导致开发新的诊断和治疗靶点。