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

doi:10.1016/j.jaci.2022.11.032

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 journal › Journal article › peer-review

13 Citations (Scopus)

Abstract

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 language	English
Pages (from-to)	1259-1268
Number of pages	10
Journal	Journal of Allergy and Clinical Immunology
Volume	151
Issue number	5
Early online date	2 Feb 2023
DOIs	https://doi.org/10.1016/j.jaci.2022.11.032
Publication status	Published - May 2023

Scopus Subject Areas

Immunology and Allergy
Immunology

User-Defined Keywords

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

UN SDGs

This output contributes to the following UN Sustainable Development Goals (SDGs)

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10.1016/j.jaci.2022.11.032

Cite this

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title = "Phospholipid remodeling and its derivatives are associated with COVID-19 severity",

abstract = "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{\textquoteright}s severity and pathogenesis.",

keywords = "COVID-19, lipidomics, LPC 16:1, LPE 18:1, phospholipid ratio",

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

note = "Supported by the National Natural Science Foundation of China (grants 22106108, U1801286, 31770984, 81901634), the Natural Science Foundation of Guangdong Province (2019A1515110407), the Shenzhen Science and Technology Peacock Team Project (KQTD20170331145453160), the China Postdoctoral Science Foundation (2021M690785), the Key Science and Technology Project of Shenzhen (JSGG20200225153031960), and the Retired Experts Program of Guangdong Province (2020A1313030065). Publisher Copyright: {\textcopyright} 2023 American Academy of Allergy, Asthma & Immunology",

year = "2023",

month = may,

doi = "10.1016/j.jaci.2022.11.032",

language = "English",

volume = "151",

pages = "1259--1268",

journal = "Journal of Allergy and Clinical Immunology",

issn = "0091-6749",

publisher = "Mosby Inc.",

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TY - JOUR

T1 - Phospholipid remodeling and its derivatives are associated with COVID-19 severity

AU - Wei, Juntong

AU - Liu, Xiaoyu

AU - Xiao, Weimin

AU - Lu, Jiahua

AU - Guan, Li

AU - Fang, Zhangfu

AU - Chen, Jiaping

AU - Sun, Baoqing

AU - Cai, Zongwei

AU - Sun, Xizhuo

AU - Chen, Hua Ling

AU - Zhong, Nanshan

AU - Liu, Zhigang

AU - Yang, Jun

AU - Xiao, Xiaojun

AU - Huang, Shau Ku

N1 - Supported by the National Natural Science Foundation of China (grants 22106108, U1801286, 31770984, 81901634), the Natural Science Foundation of Guangdong Province (2019A1515110407), the Shenzhen Science and Technology Peacock Team Project (KQTD20170331145453160), the China Postdoctoral Science Foundation (2021M690785), the Key Science and Technology Project of Shenzhen (JSGG20200225153031960), and the Retired Experts Program of Guangdong Province (2020A1313030065). Publisher Copyright: © 2023 American Academy of Allergy, Asthma & Immunology

PY - 2023/5

Y1 - 2023/5

N2 - 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.

AB - 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.

KW - COVID-19

KW - lipidomics

KW - LPC 16:1

KW - LPE 18:1

KW - phospholipid ratio

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U2 - 10.1016/j.jaci.2022.11.032

DO - 10.1016/j.jaci.2022.11.032

M3 - Journal article

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AN - SCOPUS:85148856257

SN - 0091-6749

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JO - Journal of Allergy and Clinical Immunology

JF - Journal of Allergy and Clinical Immunology

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ER -

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

Abstract

Scopus Subject Areas

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UN SDGs

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