Association of serum ADMA, SDMA and L-NMMA concentrations with disease progression in COVID-19 patients

Biochem Med (Zagreb). 2023 Feb 15;33(1):010701. doi: 10.11613/BM.2023.010701. Epub 2022 Dec 15.


Introduction: This study determines and compares the concentrations of arginine and methylated arginine products ((asymmetric dimethylarginine (ADMA), symmetric dimethylarginine (SDMA), n-monomethyl-1-arginine (L-NMMA) and homoarginine (HA)) for assessment of their association with disease severity in serum samples of COVID-19 patients.

Materials and methods: Serum arginine and methylated arginine products of 57 mild-moderate and 29 severe (N = 86) COVID-19 patients and 21 controls were determined by tandem mass spectrometry. Moreover, the concentrations of some of the routine clinical laboratory parameters -neutrophil lymphocyte ratio (NLR), C-reactive protein, ferritin, D-dimer, and fibrinogen measured during COVID-19 follow-up were also taken into consideration and compared with the concentrations of arginine and methylated arginine products.

Results: Serum ADMA, SDMA and L-NMMA were found to be significantly higher in severe COVID-19 patients, than in both mild-moderate patients and the control group (P < 0.001 for each). In addition, multiple logistic regression analysis indicated L-NMMA (cut-off =120 nmol/L OR = 34, 95% confidence interval (CI) = 3.5-302.0, P= 0.002), CRP (cut-off = 32 mg/L, OR = 37, 95% CI = 4.8-287.0, P < 0.001), and NLR (cut-off = 7, OR = 22, 95% CI = 1.4-335.0, P = 0.020) as independent risk factors for identification of severe patients.

Conclusions: The concentration of methylated arginine metabolites are significantly altered in COVID-19 disease. The results of this study indicate a significant correlation between the severity of COVID-19 disease and concentrations of CRP, NLR and L-NMMA.

Keywords: N-monomethyl-1 -arginine (L-NMMA); SARS-CoV-2; asymmetric dimethylarginine (ADMA); prognosis.

MeSH terms

  • Arginine* / blood
  • COVID-19* / blood
  • COVID-19* / diagnosis
  • Disease Progression
  • Humans
  • omega-N-Methylarginine


  • Arginine
  • N,N-dimethylarginine
  • omega-N-Methylarginine
  • symmetric dimethylarginine