Effect of a Functional Phospholipid Metabolome-Protein Association Pathway on the Mechanism of COVID-19 Disease Progression

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.

Developing A Baseline Metabolomic Signature Associated with COVID-19 Severity: Insights from Prospective Trials Encompassing 13 U.S. Centers

“…Our study identified metabolites that include three lipid species (lysophosphatidylcholine a C17:0, dihydroceramide (d18:0/24:1), and triacylglyceride (20:4_36:4)), a modulator of nitric oxide synthesis (symmetric dimethylarginine (SDMA)), and a neurotransmitter (gamma-aminobutyric acid (GABA)). Many metabolomics studies of COVID patients have now reported significant alterations to lipids related to disease severity [10,11,26,28,29,[33][34][35], and disruptions to lipid metabolism may persist for years in patients with long COVID [36]. Our data are consistent with these findings.…”

“…However, the effect of LysoPC molecules on inflammation remains controversial. Both proinflammatory [23,25] and anti-inflammatory [26][27][28][29][30][31][32] effects of the LysoPC molecules have been reported previously. Our results are in agreement with other studies showing that LysoPC levels are lower in patients with more severe COVID-19 [26,28,29].…”

“…Both proinflammatory [23,25] and anti-inflammatory [26][27][28][29][30][31][32] effects of the LysoPC molecules have been reported previously. Our results are in agreement with other studies showing that LysoPC levels are lower in patients with more severe COVID-19 [26,28,29]. A summary of all the LysoPC molecules in our analysis can be found in Supplementary Table S4.…”

ERC-BiP Functional Protein Pathway for Assessing Endoplasmic Reticulum Stress Induced by SARS-CoV-2 Replication after Cell Invasion

“…Clinical data and blood samples of patients were collected at admission and one week after admission [ 14 ]. The patients were divided into two groups based on their conditions at the two time points, except for 5 patients without longitudinal samples, as follows: the aggravation group ( n = 29) (patients with significant respiratory symptom exacerbation, increased area of pulmonary imaging lesions, and decreased oxygenation index after admission) and the remission group ( n = 12) (patients with reduced symptoms, decreased pulmonary lesions, or improved clinical indices).…”

COVID-19, Blood Lipid Changes, and Thrombosis

“…The other product of PLA 2 action on phospholipids apart from ARA is lysophospholids. Analyses of the plasma of COVID-19 patients using metabolomic and proteomic approaches showed that 30 out of 33 metabolites analysed differed significantly between patients and healthy controls [ 113 ]. LysoPC and LysoPE levels were significantly higher in COVID-19 patients at high risk for thromboses than in patients at low risk (D-dimer ≤ 900 U/mL) [ 113 ].…”