Int J Biol Sci 2022; 18(12):4618-4628. doi:10.7150/ijbs.72450 This issue

Research Paper

Effect of a Functional Phospholipid Metabolome-Protein Association Pathway on the Mechanism of COVID-19 Disease Progression

Mingshan Xue1,2#, Teng Zhang4#, Zhangkai J. Cheng2#, Baojun Guo2, Yifeng Zeng3, Runpei Lin3, Peiyan Zheng3, Mingtao Liu2, Fengyu Hu1, Feng Li1, Wensheng Zhang5, Lu Li1, Qi Zhao4✉, Baoqing Sun3✉, Xiaoping Tang1,2✉

1. Guangzhou Eighth People's Hospital, Guangzhou Medical University, Guangzhou, 510060, China.
2. Guangzhou Laboratory, XingDaoHuanBei Road, Guangzhou International Bio Island, Guangzhou 510005, Guangdong Province, China.
3. National Center for Respiratory Medicine, The First Affiliated Hospital of Guangzhou Medical University, National Clinical Research Center for Respiratory Disease, State Key Laboratory of Respiratory Disease, Guangzhou Institute of Respiratory Health, Guangzhou 510120, China.
4. MoE Frontiers Science Center for Precision Oncology, Cancer Centre, Institute of Translational Medicine, Faculty of Health Sciences, University of Macau. Taipa, Macau, China.
5. Institue of automation Chinese Academy of Sciences, Beijing, China.
#These authors contributed equally to this work.

This is an open access article distributed under the terms of the Creative Commons Attribution License ( See for full terms and conditions.
Xue M, Zhang T, Cheng ZJ, Guo B, Zeng Y, Lin R, Zheng P, Liu M, Hu F, Li F, Zhang W, Li L, Zhao Q, Sun B, Tang X. Effect of a Functional Phospholipid Metabolome-Protein Association Pathway on the Mechanism of COVID-19 Disease Progression. Int J Biol Sci 2022; 18(12):4618-4628. doi:10.7150/ijbs.72450. Available from

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Graphic abstract

This study aimed to explore the clinical practice of phospholipid metabolic pathways in COVID-19. In this study, 48 COVID-19 patients and 17 healthy controls were included. Patients were divided into mild (n=40) and severe (n=8) according to their severity. Phospholipid metabolites, TCA circulating metabolites, eicosanoid metabolites, and closely associated enzymes and transfer proteins were detected in the plasma of all individuals using metabolomics and proteomics assays, respectively. 30 of the 33 metabolites found differed significantly (P<0.05) between patients and healthy controls (P<0.05), with D-dimmer significantly correlated with all of the lysophospholipid metabolites (LysoPE, LysoPC, LysoPI and LPA). In particular, we found that phosphatidylinositol (PI) and phosphatidylcholine (PC) could identify patients from healthy controls (AUC 0.771 and 0.745, respectively) and that the severity of the patients could be determined (AUC 0.663 and 0.809, respectively). The last measurement before discharge also revealed significant changes in both PI and PC. For the first time, our study explores the significance of the phospholipid metabolic system in COVID-19 patients. Based on molecular pathway mechanisms, three important phospholipid pathways related to Ceramide-Malate acid (Cer-SM), Lysophospholipid (LPs), and membrane function were established. Clinical values discovered included the role of Cer in maintaining the inflammatory internal environment, the modulation of procoagulant LPA by upstream fibrinolytic metabolites, and the role of PI and PC in predicting disease aggravation.

Keywords: COVID-19, phospholipid metabolic pathway, eicosanoic acids, metabolomics