Dynamic modulations of sphingolipids and glycerophospholipids in COVID‐19

Abstract

Background A heterogeneous clinical phenotype is a characteristic of coronavirus disease 2019 (COVID‐19). Therefore, investigating biomarkers associated with disease severity is important for understanding the mechanisms responsible for this heterogeneity and for developing novel agents to prevent critical conditions. This study aimed to elucidate the modulations of sphingolipids and glycerophospholipids, which have been shown to possess potent biological properties. Methods We measured the serum sphingolipid and glycerophospholipid levels in a total of 887 samples from 215 COVID‐19 subjects, plus 115 control subjects without infectious diseases and 109 subjects with infectious diseases other than COVID‐19. Results We observed the dynamic modulations of sphingolipids and glycerophospholipids in the serum of COVID‐19 subjects, depending on the time course and severity. The elevation of C16:0 ceramide and lysophosphatidylinositol and decreases in C18:1 ceramide, dihydrosphingosine, lysophosphatidylglycerol, phosphatidylglycerol and phosphatidylinositol were specific to COVID‐19. Regarding the association with maximum severity, phosphatidylinositol and phosphatidylcholine species with long unsaturated acyl chains were negatively associated, while lysophosphatidylethanolamine and phosphatidylethanolamine were positively associated with maximum severity during the early phase. Lysophosphatidylcholine and phosphatidylcholine had strong negative correlations with CRP, while phosphatidylethanolamine had strong positive ones. C16:0 ceramide, lysophosphatidylcholine, phosphatidylcholine and phosphatidylethanolamine species with long unsaturated acyl chains had negative correlations with D‐dimer, while phosphatidylethanolamine species with short acyl chains and phosphatidylinositol had positive ones. Several species of phosphatidylcholine, phosphatidylethanolamine and sphingomyelin might serve as better biomarkers for predicting severe COVID‐19 during the early phase than CRP and D‐dimer. Compared with the lipid modulations seen in mice treated with lipopolysaccharide, tissue factor, or histone, the lipid modulations observed in severe COVID‐19 were most akin to those in mice administered lipopolysaccharide. Conclusion A better understanding of the disturbances in sphingolipids and glycerophospholipids observed in this study will prompt further investigation to develop laboratory testing for predicting maximum severity and/or novel agents to suppress the aggravation of COVID‐19.

Dynamic modulations of urinary sphingolipid and glycerophospholipid levels in COVID-19 and correlations with COVID-19-associated kidney injuries

“…Regarding the PE-LPE axis, LPE increased from the early phase (day 4-6) and reached a peak on day 10-12 in maximum severity group 2. In maximum severity group 3, LPE increased, especially during the later phase (day[19][20][21][22][23][24]. The urinary total PE levels were modulated in an almost similar manner to those of LPE.…”

“…Although several lipidomics analyses using serum or plasma samples from patients with COVID-19 have been performed [23], only one lipidomics study has been conducted using urine samples from a very small number of COVID-19 patients [31]. With this background in mind, we performed lipidomic analyses using urine samples to investigate the mechanisms responsible for COVID-19-associated kidney injuries to understand the pathogenesis of COVID-19 and COVID-19-associated kidney injuries, as well as AKI, better and to help researchers develop reagents capable of preventing severe kidney injuries in the future.…”

Deep phenotyping of the lipidomic response in COVID‐19 and non‐COVID‐19 sepsis

“…This has been true also in COVID- 19 where the high abundance lipidome has been implicated in prognosis, 9 pathogenesis 10 and disease severity. [11][12][13][14][15][16][17][18][19][20] Relatively few reports have focused on eicosanoids, less abundant oxylipins that act locally, but are nonetheless powerful modulators of the immune response. 4 Elevated levels of eicosanoids have been reported in plasma, 21 tracheal aspirate, 22 urine 23 and in stimulated peripheral blood monocytes 24 of patients with severe COVID-19.…”

Metabolomics as a powerful tool for diagnostic, pronostic and drug intervention analysis in COVID-19

“…Other studies also suggest a slower metabolic phenoreversion as compared to the patient’s discharge time ( Zhang et al, 2021 ), with dysregulated lipoprotein profile after hospital discharge ( Bizkarguenaga et al, 2022 ). Persistent alterations of the metabolism concentrate in the amino acids, organic acids, purine, fatty acids ( Valdés et al, 2022 ) and lipid metabolism ( Kurano et al, 2022a ), while the kynurenate pathway returned to normal levels ( Li F. et al, 2022 ).…”