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

Abstract

Background Among various complications of coronavirus disease 2019 (COVID-19), caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), renal complications, namely COVID-19-associated kidney injuries, are related to the mortality of COVID-19. Methods In this retrospective cross-sectional study, we measured the sphingolipids and glycerophospholipids, which have been shown to possess potent biological properties, using liquid chromatography-mass spectrometry in 272 urine samples collected longitudinally from 91 COVID-19 subjects and 95 control subjects without infectious diseases, to elucidate the pathogenesis of COVID-19-associated kidney injuries. Results The urinary levels of C18:0, C18:1, C22:0, and C24:0 ceramides, sphingosine, dihydrosphingosine, phosphatidylcholine, lysophosphatidylcholine, lysophosphatidic acid, and phosphatidylglycerol decreased, while those of phosphatidylserine, lysophosphatidylserine, phosphatidylethanolamine, and lysophosphatidylethanolamine increased in patients with mild COVID-19, especially during the early phase (day 1–3), suggesting that these modulations might reflect the direct effects of infection with SARS-CoV-2. Generally, the urinary levels of sphingomyelin, ceramides, sphingosine, dihydrosphingosine, dihydrosphingosine l-phosphate, phosphatidylcholine, lysophosphatidic acid, phosphatidylserine, lysophosphatidylserine, phosphatidylethanolamine, lysophosphatidylethanolamine, phosphatidylglycerol, lysophosphatidylglycerol, phosphatidylinositol, and lysophosphatidylinositol increased, especially in patients with severe COVID-19 during the later phase, suggesting that their modulations might result from kidney injuries accompanying severe COVID-19. Conclusions Considering the biological properties of sphingolipids and glycerophospholipids, an understanding of their urinary modulations in COVID-19 will help us to understand the mechanisms causing COVID-19-associated kidney injuries as well as general acute kidney injuries and may prompt researchers to develop laboratory tests for predicting maximum severity and/or novel reagents to suppress the renal complications of COVID-19.

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

“…While perturbation of the serum lipidome by infections is well documented, 4–8 attention has focused on high abundance lipids such as phospholipids, ceramides and sphingomyelins. This has been true also in COVID‐19 where the high abundance lipidome has been implicated in prognosis, 9 pathogenesis 10 and disease severity 11–20 …”

“…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.…”

Alzheimer’s disease manifests abnormal sphingolipid metabolism

“…Sphingolipids are among the well-studied bioactive lipid mediators, playing crucial roles in the physiology and pathology of human diseases ( Kluk and Hla, 2002 ; Hla, 2003 ; Nakamura et al, 2021 ; Kurano et al, 2022a , b , d ; Uranbileg et al, 2022 ). In the field of neurology, their structural role in cellular membranes, particularly in lipid rafts, is a crucial aspect of their interaction with the amyloid beta (Aβ) metabolism ( Olsen and Faergeman, 2017 ), suggesting the potential to investigate their role in AD.…”

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

“…In terms of the nature of the specimen, serum and plasma followed by urine ( Kurano et al, 2022b ; Kida et al, 2022 ) are the most studied biofluids, while other samples also scrutinized include saliva ( Spick et al, 2022b ; Frampas et al, 2022 ; Saheb Sharif-Askari et al, 2022 ), faeces ( He et al, 2021 ; Lv et al, 2021 ; Ren et al, 2021 ), platelets ( Schuurman et al, 2022 ), exhaled breath ( Barberis et al, 2021a ; Grassin-Delyle et al, 2021 ; Bennet et al, 2022 ; Remy et al, 2022 ), sebum from skin ( Spick et al, 2021 ) and breastmilk ( Zhao et al, 2020 ). Due to the high volume of information ( Table 1 ), we here complement other recent reviews on COVID-19 metabolomics ( Hasan et al, 2021 ; Lin et al, 2021 ; Costanzo et al, 2022 ) by selecting a set of contributions to be discussed in the present review, based on our evaluation of novelty, impact and originality.…”