COVID-19, Blood Lipid Changes, and Thrombosis

Akhlaq A Farooqui; Tahira Farooqui; Grace Y Sun; Teng-Nan Lin; Daniel B L Teh; Wei-Yi Ong

doi:10.3390/biomedicines11041181

COVID-19, Blood Lipid Changes, and Thrombosis

Biomedicines. 2023 Apr 15;11(4):1181. doi: 10.3390/biomedicines11041181.

Authors

Akhlaq A Farooqui¹, Tahira Farooqui¹, Grace Y Sun², Teng-Nan Lin³, Daniel B L Teh^{4

5

6}, Wei-Yi Ong^{5

6}

Affiliations

¹ Department of Molecular and Cellular Biochemistry, Ohio State University, Columbus, OH 43210, USA.
² Department of Biochemistry, University of Missouri, Columbia, MO 65211, USA.
³ Institute of Biomedical Sciences, Academia Sinica, Taipei 11929, Taiwan.
⁴ Department of Ophthalmology, Yong Loo Lin School of Medicine, National University of Singapore, Singapore 119260, Singapore.
⁵ Department of Anatomy, Yong Loo Lin School of Medicine, National University of Singapore, Singapore 119260, Singapore.
⁶ Neurobiology Research Programme, Life Sciences Institute, National University of Singapore, Singapore 119260, Singapore.

Abstract

Although there is increasing evidence that oxidative stress and inflammation induced by COVID-19 may contribute to increased risk and severity of thromboses, the underlying mechanism(s) remain to be understood. The purpose of this review is to highlight the role of blood lipids in association with thrombosis events observed in COVID-19 patients. Among different types of phospholipases A₂ that target cell membrane phospholipids, there is increasing focus on the inflammatory secretory phospholipase A₂ IIA (sPLA₂-IIA), which is associated with the severity of COVID-19. Analysis indicates increased sPLA₂-IIA levels together with eicosanoids in the sera of COVID patients. sPLA₂ could metabolise phospholipids in platelets, erythrocytes, and endothelial cells to produce arachidonic acid (ARA) and lysophospholipids. Arachidonic acid in platelets is metabolised to prostaglandin H2 and thromboxane A₂, known for their pro-coagulation and vasoconstrictive properties. Lysophospholipids, such as lysophosphatidylcholine, could be metabolised by autotaxin (ATX) and further converted to lysophosphatidic acid (LPA). Increased ATX has been found in the serum of patients with COVID-19, and LPA has recently been found to induce NETosis, a clotting mechanism triggered by the release of extracellular fibres from neutrophils and a key feature of the COVID-19 hypercoagulable state. PLA2 could also catalyse the formation of platelet activating factor (PAF) from membrane ether phospholipids. Many of the above lipid mediators are increased in the blood of patients with COVID-19. Together, findings from analyses of blood lipids in COVID-19 patients suggest an important role for metabolites of sPLA₂-IIA in COVID-19-associated coagulopathy (CAC).

Keywords: C16:0 ceramide; CAC; COVID-19; COVID-19-associated-coagulopathy; LPA; NETs; PLA2G2A; autotaxin; brain endothelial cells; lysophosphatidic acid; lysophospholipase D; macrothrombi; microthrombi; neutrophil extracellular traps; platelets; pneumocytes; sPLA2-IIA; secretory phospholipase A2; stroke; thrombosis.

Publication types

Review

Grants and funding

This research was supported by a grant from the National Medical Research Council of Singapore (Catalyst Grant, HLCA21Jan-0019, WYO).