Urea Cycle and Arginine Metabolic Changes in COVID-19 Patients

Abstract

Aim:Metabolic changes begin after the invasion of an infectious microorganism and continue to develop as a series of interrelated events. Arginine is important in infectious diseases due to lymphocyte proliferation, nitricoxide production by macrophages, and the use of polyamides in the immune response. In this study, we aimed to examine the possible causes and consequences of urea cycle amino acid metabolism changes by comparing plasma arginine and urea cycle amino acid levels in Coronavirus disease-2019 (COVID-19) patients.Materials and Methods:In this cross-sectional study, we evaluated the urea cycle and arginine metabolic changes and compared the plasma aminoacid levels of 35 COVID-19 patients and a healthy control group (n=35). The patient was diagnosed by reverse transcriptase-polymerase chain reaction of oropharyngeal-nasofaringeal swab specimens. For statistical analyzes, Mann-Whitney U and chi-square tests were used.Results:The aminoacid plasma levels of argininosuccinate (1.03 μmol/L, p=3.3x10-3), arginine (53.64 μmol/L, p=1.1x10-3), aspartic acid (3.83 μmol/L, p=5.5x10-9), citrulline (27.79 μmol/L, p=3.3x10-5), glutamine (489.6 μmol/L, p=9.0x10-17), lysine (206.4 μmol/L, p=5.8x10-8), ornithine (129.5 μmol/L, p=0.012), plasma levels and glutamine/glutamate (p=3.4x10-11), arg/ornithine (p=0.033), asp/argininosuccinate (p=0.011) ratios were decreased in the COVID-19 patient group compared to the healthy group.Conclusion:Arginine is significant in endothelial control, the urea cycle, and immune activation. Arginine deficiency in COVID-19 patients may cause disturbances in this biological process and its pathways. As indicated by many clinical trials, we believe that preventing a decrease in plasma arginine levels will prevent a poor prognosis of patients and metabolic pathway disturbances in the urea cycle.

Keywords

• urea cycle
• arginine
• covid-19
• glutamine
• citrulline
• ornithine
• virus disease