Modified Proline Metabolism and Prolidase Enzyme in COVID-19

Abstract

Objective The aim of the study was to evaluate proline metabolism in patients affected by COVID-19. Materials and Methods This case-control study consisted of 116 patients with COVID-19 and 46 healthy individuals. Tests related to proline metabolism (prolidase, proline, hydroxyproline, glutamic acid, manganese) and copper and zinc tests were analyzed. Results The levels of proline and hydroxyproline amino acids and the prolidase enzyme were found to be lower and glutamic acid was found to be higher in the COVID-19 group compared to the healthy group (P = .012, P < .001, P < .001, and P < .001, respectively). The copper/zinc ratio was higher in patients with COVID-19 than in healthy individuals (P < .001). Significant correlations were found between proline metabolism tests and inflammatory and hemostatic markers commonly used in COVID-19. Conclusion The proline metabolic pathway was affected in COVID-19. Relationships between proline pathway–related tests and inflammatory/hemostatic markers supported the roles of proline metabolism in proinflammatory and immune response processes.

Metabolomics analysis identifies glutamic acid and cystine imbalances in COVID-19 patients without comorbid conditions. Implications on redox homeostasis and COVID-19 pathophysiology

“…In agreement with findings from other studies [ 1 , 2 , 79 – 81 ], we detected decreased proline levels in those patients with severe COVID-19 studies. In this vein, it has been shown that decreased proline levels are associated with an unfavorable prognosis in patients with the severe form of this disease [ 80 , 82 ].…”

The Associations of Iron Related Biomarkers with Risk, Clinical Severity and Mortality in SARS-CoV-2 Patients: A Meta-Analysis

“…Then the "leave-oneout" sensitivity analyses used I 2 > 50% as the criterion to evaluate the robustness of conclusion of ferritin. Twelve studies [8,38,47,48,51,55,[57][58][59][60]62] on mortality (Figure 12) and four [17,20,21,24] studies on risk (Figure 13) were found to be the main reasons for the high heterogeneity. After excluding these studies, low heterogeneity and robust results without the small-study effect were demonstrated for mortality (SMD = 0; Z = 7.47; p < 0.001; I 2 = 44.2%) and risk (SMD = 0; Z = 7.39; p < 0.001; I 2 = 44.8%) analyses of ferritin.…”

“…Figure 13. Galbraith plot for the contribution of results from the different studies [10,[17][18][19][20][21]24,36,37,[42][43][44]72] about risk for ferritin to the heterogeneity. This analysis was based on the relevant data listed in Table1 and the number orders in the plot were same to the reference list.…”

“…Previous studies have investigated the relationships among iron, ferritin, hemoglobin, hepcidin, TIBC, TSAT and COVID-19, but their results are conflicting and inconsistent. Most studies about serum iron have shown that lower iron levels are found in more at-risk groups, such as non-survivors compared to survivors [8][9][10][11][12][13], severe disease groups compared to non-severe disease groups [10,[13][14][15][16] and cases to controls [10,[16][17][18][19][20][21], whereas others expressed the opposite results [7,22,23]. In all relevant studies, the hemoglobin levels were found to be lower in severe groups than those in controls [7,10,24] or non-severe groups [22,[25][26][27][28][29].…”

“…Lower levels of hepcidin in cases than controls was documented in a study [10], whereas the other studies reported an inverse result [18,20,24]. Unusually, more dangerous groups had higher ferritin levels in almost all relevant comparisons [4,6,[10][11][12][13][14][15][17][18][19][20][21][22][24][25][26][27][28][29][30]32,[34][35][36][37][38][39][40].…”