Alterations in the Kynurenine-Tryptophan Pathway and Lipid Dysregulation Are Preserved Features of COVID-19 in Hemodialysis

• Published in: International journal of molecular sciences 2022-11, Vol.23 (22), p.14089
• Main Authors: Schuller, Max, Oberhuber, Monika, Prietl, Barbara, Zügner, Elmar, Prugger, Eva-Maria, Magnes, Christoph, Kirsch, Alexander H, Schmaldienst, Sabine, Pieber, Thomas, Brodmann, Marianne, Rosenkranz, Alexander R, Eller, Philipp, Eller, Kathrin
• Format: Article
• Language: English
• Subjects: Asymptomatic; Biomarkers; Chemokines; Coronaviruses; COVID-19; Creatinine; Cytokines; End-stage renal disease; Fatty acids; Hemodialysis; hemodialysis patients; Humans; Intensive care; Intercellular adhesion molecule 1; Interleukin 15; Kidney diseases; Kidneys; Kynurenine; lipid dysregulation; Lipids; Metabolism; Metabolites; Metabolomics; Patients; Renal Dialysis; Severe acute respiratory syndrome coronavirus 2; Tryptophan
• ISSN: 1422-0067; 1661-6596; 1422-0067
• DOI: 10.3390/ijms232214089

Coronavirus disease 2019 (COVID-19)-induced metabolic alterations have been proposed as a source for prognostic biomarkers and may harbor potential for therapeutic exploitation. However, the metabolic impact of COVID-19 in hemodialysis (HD), a setting of profound a priori alterations, remains unstudied. To evaluate potential COVID-19 biomarkers in end-stage kidney disease (CKD G5), we analyzed the plasma metabolites in different COVID-19 stages in patients with or without HD. We recruited 18 and 9 asymptomatic and mild, 11 and 11 moderate, 2 and 13 severely affected, and 10 and 6 uninfected HD and non-HD patients, respectively. Plasma samples were taken at the time of diagnosis and/or upon admission to the hospital and analyzed by targeted metabolomics and cytokine/chemokine profiling. Targeted metabolomics confirmed stage-dependent alterations of the metabolome in non-HD patients with COVID-19, which were less pronounced in HD patients. Elevated kynurenine levels and lipid dysregulation, shown by an increase in circulating free fatty acids and a decrease in lysophospholipids, could distinguish patients with moderate COVID-19 from non-infected individuals in both groups. Kynurenine and lipid alterations were also associated with ICAM-1 and IL-15 levels in HD and non-HD patients. Our findings support the kynurenine pathway and plasma lipids as universal biomarkers of moderate and severe COVID-19 independent of kidney function.