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.