Significance of nitrosative stress and glycoxidation products in the diagnosis of COVID-19

Sci Rep. 2024 Apr 22;14(1):9198. doi: 10.1038/s41598-024-59876-w.

Abstract

Nitrosative stress promotes protein glycoxidation, and both processes can occur during an infection with the SARS-CoV-2 virus. Therefore, the aim of this study was to assess selected nitrosative stress parameters and protein glycoxidation products in COVID-19 patients and convalescents relative to healthy subjects, including in reference to the severity of COVID-19 symptoms. The diagnostic utility of nitrosative stress and protein glycoxidation biomarkers was also evaluated in COVID-19 patients. The study involved 218 patients with COVID-19, 69 convalescents, and 48 healthy subjects. Nitrosative stress parameters (NO, S-nitrosothiols, nitrotyrosine) and protein glycoxidation products (tryptophan, kynurenine, N-formylkynurenine, dityrosine, AGEs) were measured in the blood plasma or serum with the use of colorimetric/fluorometric methods. The levels of NO (p = 0.0480), S-nitrosothiols (p = 0.0004), nitrotyrosine (p = 0.0175), kynurenine (p < 0.0001), N-formylkynurenine (p < 0.0001), dityrosine (p < 0.0001), and AGEs (p < 0.0001) were significantly higher, whereas tryptophan fluorescence was significantly (p < 0.0001) lower in COVID-19 patients than in the control group. Significant differences in the analyzed parameters were observed in different stages of COVID-19. In turn, the concentrations of kynurenine (p < 0.0001), N-formylkynurenine (p < 0.0001), dityrosine (p < 0.0001), and AGEs (p < 0.0001) were significantly higher, whereas tryptophan levels were significantly (p < 0.0001) lower in convalescents than in healthy controls. The ROC analysis revealed that protein glycoxidation products can be useful for diagnosing infections with the SARS-CoV-2 virus because they differentiate COVID-19 patients (KN: sensitivity-91.20%, specificity-92.00%; NFK: sensitivity-92.37%, specificity-92.00%; AGEs: sensitivity-99,02%, specificity-100%) and convalescents (KN: sensitivity-82.22%, specificity-84.00%; NFK: sensitivity-82,86%, specificity-86,00%; DT: sensitivity-100%, specificity-100%; AGE: sensitivity-100%, specificity-100%) from healthy subjects with high sensitivity and specificity. Nitrosative stress and protein glycoxidation are intensified both during and after an infection with the SARS-CoV-2 virus. The levels of redox biomarkers fluctuate in different stages of the disease. Circulating biomarkers of nitrosative stress/protein glycoxidation have potential diagnostic utility in both COVID-19 patients and convalescents.

Keywords: COVID-19; Glycoxidation products; MEWS; Nitrosative stress; SARS-CoV-2 virus.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adult
  • Aged
  • Biomarkers* / blood
  • COVID-19* / blood
  • COVID-19* / diagnosis
  • COVID-19* / metabolism
  • Female
  • Glycation End Products, Advanced / blood
  • Glycation End Products, Advanced / metabolism
  • Humans
  • Kynurenine / analogs & derivatives*
  • Kynurenine / blood
  • Kynurenine / metabolism
  • Male
  • Middle Aged
  • Nitric Oxide / blood
  • Nitric Oxide / metabolism
  • Nitrosative Stress*
  • ROC Curve
  • S-Nitrosothiols / blood
  • S-Nitrosothiols / metabolism
  • SARS-CoV-2*
  • Tryptophan / analogs & derivatives
  • Tryptophan / blood
  • Tryptophan / metabolism
  • Tyrosine* / analogs & derivatives*
  • Tyrosine* / blood
  • Tyrosine* / metabolism

Substances

  • Biomarkers
  • Tyrosine
  • 3-nitrotyrosine
  • Kynurenine
  • S-Nitrosothiols
  • Nitric Oxide
  • Tryptophan
  • N'-formylkynurenine
  • dityrosine
  • Glycation End Products, Advanced