Phospholipid remodeling and its derivatives are associated with COVID-19 severity

Juntong Wei, Xiaoyu Liu, Weimin Xiao, Jiahua Lu, Li Guan, Zhangfu Fang, Jiaping Chen, Baoqing Sun, Zongwei Cai, Xizhuo Sun, Hua Ling Chen, Nanshan Zhong, Zhigang Liu, Jun Yang*, Xiaojun Xiao*, Shau Ku Huang*

*Corresponding author for this work

Research output: Contribution to journalJournal articlepeer-review

8 Citations (Scopus)


Background: Timely medical intervention in severe cases of coronavirus disease 2019 (COVID-19) and better understanding of the disease's pathogenesis are essential for reducing mortality, but early classification of severe cases and its progression is challenging. 

Objective: We investigated the levels of circulating phospholipid metabolites and their relationship with COVID-19 severity, as well as the potential role of phospholipids in disease progression. 

Methods: We performed nontargeted lipidomic analysis of plasma samples (n = 150) collected from COVID-19 patients (n = 46) with 3 levels of disease severity, healthy individuals, and subjects with metabolic disease. 

Results: Phospholipid metabolism was significantly altered in COVID-19 patients. Results of a panel of phosphatidylcholine (PC) and lysophosphatidylcholine (LPC) and of phosphatidylethanolamine and lysophosphatidylethanolamine (LPE) ratios were significantly correlated with COVID-19 severity, in which 16 phospholipid ratios were shown to distinguish between patients with severe disease, mild disease, and healthy controls, 9 of which were at variance with those in subjects with metabolic disease. In particular, relatively lower ratios of circulating (PC16:1/22:6)/LPC 16:1 and (PE18:1/22:6)/LPE 18:1 were the most indicative of severe COVID-19. The elevation of levels of LPC 16:1 and LPE 18:1 contributed to the changes of related lipid ratios. An exploratory functional study of LPC 16:1 and LPE 18:1 demonstrated their ability in causing membrane perturbation, increased intracellular calcium, cytokines, and apoptosis in cellular models. 

Conclusion: Significant Lands cycle remodeling is present in patients with severe COVID-19, suggesting a potential utility of selective phospholipids with functional consequences in evaluating COVID-19’s severity and pathogenesis.

Original languageEnglish
Pages (from-to)1259-1268
Number of pages10
JournalJournal of Allergy and Clinical Immunology
Issue number5
Early online date2 Feb 2023
Publication statusPublished - May 2023

Scopus Subject Areas

  • Immunology and Allergy
  • Immunology

User-Defined Keywords

  • COVID-19
  • lipidomics
  • LPC 16:1
  • LPE 18:1
  • phospholipid ratio


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