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Phospholipid remodeling and its derivatives are associated with COVID-19 severity - 04/05/23

Doi : 10.1016/j.jaci.2022.11.032 
Juntong Wei, PhD a, b, Xiaoyu Liu, PhD b, Weimin Xiao, PhD c, Jiahua Lu, MMed b, Li Guan, MD, PhD a, Zhangfu Fang, MD, PhD a, b, Jiaping Chen, PhD c, Baoqing Sun, MD, PhD d, Zongwei Cai, PhD e, Xizhuo Sun, MD, PhD a, Hua-Ling Chen, PhD f, Nanshan Zhong, MD, PhD d, Zhigang Liu, PhD b, , Jun Yang, PhD c, , Xiaojun Xiao, PhD b, , Shau-Ku Huang, PhD b, f, g,
a Department of Respirology and Allergy. Third Affiliated Hospital of Shenzhen University. Shenzhen, China 
b State Key Laboratory of Respiratory Disease for Allergy at Shenzhen University, Shenzhen Key Laboratory of Allergy and Immunology, Shenzhen University School of Medicine, Shenzhen, China 
c Shenzhen Academy of Metrology and Quality Inspection, Shenzhen, China 
d State Key Laboratory of Respiratory Disease, National Clinical Research Center for Respiratory Disease, Guangzhou Institute of Respiratory Health, First Affiliated Hospital of Guangzhou Medical University, Guangzhou, China 
e State Key Laboratory of Environmental and Biological Analysis, Department of Chemistry, Hong Kong Baptist University, Hong Kong, China 
f National Institute of Environmental Health Sciences, National Health Research Institutes, Miaoli County, Taiwan 
g Department of Medicine, Division of Allergy and Clinical Immunology, Johns Hopkins University School of Medicine, Baltimore, Md 

Corresponding author: Shau-Ku Huang, PhD, National Institute of Environmental Health Sciences, National Health Research Institutes, Miaoli County, Taiwan.National Institute of Environmental Health SciencesNational Health Research InstitutesMiaoli CountyTaiwan∗∗Xiaojun Xiao, PhD, Shenzhen Key Laboratory of Allergy and Immunology, Shenzhen University School of Medicine, 1066 Academic Avenue Rd, Shenzhen, China.Shenzhen Key Laboratory of Allergy and ImmunologyShenzhen University School of Medicine1066 Academic Avenue RdShenzhenChina∗∗∗Jun Yang, PhD, Shenzhen Academy of Metrology and Quality Inspection, 114 Minkang Rd, Shenzhen, China.Shenzhen Academy of Metrology and Quality Inspection114 Minkang RdShenzhenChina

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Graphical abstract




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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.

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

Abbreviations used : APACHE II, AUC, COVID-19, FDR, LPC 16:1, LPC, LPE 18:1, LPE, PC O-, PC, PE O-, PE, SARS-CoV-2


Esquema


 The first 3 authors contributed equally to this article and all should be considered first author.
 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).
 Disclosure of potential conflict of interest: The authors declare that they have no relevant conflicts of interest.


© 2023  American Academy of Allergy, Asthma & Immunology. Publicado por Elsevier Masson SAS. Todos los derechos reservados.
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