COVID-19 can result in severe lung injury. It remained to be determined why diabetic individuals with uncontrolled glucose levels are more prone to develop the severe form of COVID-19. The molecular mechanism underlying SARS-CoV-2 infection and what determines the onset of the cytokine storm found in severe COVID-19 patients are unknown. Monocytes and macrophages are the most enriched immune cell types in the lungs of COVID-19 patients and appear to have a central role in the pathogenicity of the disease. These cells adapt their metabolism upon infection and become highly glycolytic, which facilitates SARS-CoV-2 replication. The infection triggers mitochondrial ROS production, which induces stabilization of hypoxia-inducible factor-1α (HIF-1α) and consequently promotes glycolysis. HIF-1α-induced changes in monocyte metabolism by SARS-CoV-2 infection directly inhibit T cell response and reduce epithelial cell survival. Targeting HIF-1ɑ may have great therapeutic potential for the development of novel drugs to treat COVID-19.

COVID-19可导致严重的肺损伤。有待确定的原因是，为什么血糖水平不受控制的糖尿病患者更倾向于发展严重形式的COVID-19。SARS-CoV-2感染的潜在分子机制以及决定在严重COVID-19患者中发现的细胞因子风暴发作的因素尚不清楚。单核细胞和巨噬细胞是COVID-19患者肺部最丰富的免疫细胞类型，似乎在疾病的致病性中起着核心作用。这些细胞在感染后适应其新陈代谢，并具有高度的糖酵解作用，从而促进SARS-CoV-2复制。感染会触发线粒体ROS的产生，从而诱导缺氧诱导因子1α（HIF-1α）的稳定，从而促进糖酵解。HIF-1α诱导的SARS-CoV-2感染引起的单核细胞代谢变化直接抑制T细胞反应并降低上皮细胞存活率。靶向HIF-1ɑ可能具有开发治疗COVID-19的新药的巨大治疗潜力。