The COVID-19 pandemic has been the primary global health issue since its outbreak in December 2019. Patients with metabolic syndrome suffer from severe complications and a higher mortality rate due to SARS-CoV-2 infection. We recently proposed that SARS-CoV-2 can hijack host mitochondrial function and manipulate metabolic pathways for their own advantage. The aim of the current study was to investigate functional mitochondrial changes in live peripheral blood mononuclear cells (PBMCs) from COVID-19 patients, decipher the pathways of substrate utilization in these cells and corresponding changes in the inflammatory pathways. We demonstrate mitochondrial dysfunction, metabolic alterations with an increase in glycolysis and high levels of mitokine in PBMCs from COVID-19 patients. Interestingly, we found that levels of FGF-21 mitokine correlate with COVID-19 disease severity and mortality. These data suggest that COVID-19 patients have compromised mitochondrial function and an energy deficit which is compensated by a metabolic switch to glycolysis. This metabolic manipulation by SARS-CoV-2 triggers an enhanced inflammatory response which contributes to severity of symptoms in COVID-19. Targeting mitochondrial metabolic pathway(s) can help define novel strategies for COVID-19.

中文翻译：

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SARS-CoV-2 在 COVID-19 患者外周血单个核细胞中的线粒体代谢操作

自 2019 年 12 月爆发以来，COVID-19 大流行一直是全球主要的健康问题。代谢综合征患者因感染 SARS-CoV-2 而出现严重并发症，死亡率更高。我们最近提出，SARS-CoV-2 可以劫持宿主线粒体功能并操纵代谢途径以获得自身优势。本研究的目的是调查来自 COVID-19 患者的活外周血单个核细胞 (PBMC) 的功能性线粒体变化，破译这些细胞中底物利用的途径以及炎症途径的相应变化。我们在 COVID-19 患者的 PBMC 中证明了线粒体功能障碍、代谢改变和糖酵解增加以及高水平的丝裂素。有趣的是，我们发现 FGF-21 丝裂素水平与 COVID-19 疾病的严重程度和死亡率相关。这些数据表明，COVID-19 患者的线粒体功能受损和能量不足，而这种能量不足可通过代谢转换为糖酵解得到补偿。SARS-CoV-2 的这种代谢操纵引发了增强的炎症反应，导致 COVID-19 症状的严重性。针对线粒体代谢途径可以帮助定义 COVID-19 的新策略。