The pandemic of the coronavirus disease 2019 (COVID-19) has become a global public health crisis. The symptoms of COVID-19 range from mild to severe, but the physiological changes associated with COVID-19 are barely understood. In this study, we performed targeted metabolomic and lipidomic analyses of plasma from a cohort of patients with COVID-19 who had experienced different symptoms. We found that metabolite and lipid alterations exhibit apparent correlation with the course of disease in these patients, indicating that the development of COVID-19 affected their whole-body metabolism. In particular, malic acid of the TCA cycle and carbamoyl phosphate of the urea cycle result in altered energy metabolism and hepatic dysfunction, respectively. It should be noted that carbamoyl phosphate is profoundly down-regulated in patients who died compared with patients with mild symptoms. And, more importantly, guanosine monophosphate (GMP), which is mediated not only by GMP synthase but also by CD39 and CD73, is significantly changed between healthy subjects and patients with COVID-19, as well as between the mild and fatal cases. In addition, dyslipidemia was observed in patients with COVID-19. Overall, the disturbed metabolic patterns have been found to align with the progress and severity of COVID-19. This work provides valuable knowledge about plasma biomarkers associated with COVID-19 and potential therapeutic targets, as well as an important resource for further studies of the pathogenesis of COVID-19.

中文翻译：

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与 COVID-19 相关的血浆代谢组学和脂质组学改变


2019 年冠状病毒病（COVID-19）的大流行已成为全球公共卫生危机。 COVID-19 的症状从轻微到严重不等，但与 COVID-19 相关的生理变化却鲜为人知。在这项研究中，我们对一组经历过不同症状的 COVID-19 患者的血浆进行了针对性的代谢组学和脂质组学分析。我们发现代谢物和脂质的变化与这些患者的病程表现出明显的相关性，表明COVID-19的发展影响了他们的全身代谢。特别是，TCA循环的苹果酸和尿素循环的氨基甲酰磷酸分别导致能量代谢改变和肝功能障碍。值得注意的是，与症状轻微的患者相比，死亡患者的氨基甲酰磷酸水平显着下调。更重要的是，单磷酸鸟苷 (GMP) 不仅由 GMP 合酶介导，还由 CD39 和 CD73 介导，在健康受试者和 COVID-19 患者之间以及轻度病例和致命病例之间存在显着变化。此外，在 COVID-19 患者中观察到血脂异常。总体而言，代谢模式紊乱与 COVID-19 的进展和严重程度一致。这项工作提供了有关与 COVID-19 相关的血浆生物标志物和潜在治疗靶点的宝贵知识，以及进一步研究 COVID-19 发病机制的重要资源。