Evaluation of asymmetric dimethyl arginine level in patients with COVID-19 infection

COVID-19 manifests itself with milder symptoms in children. Hospitalization rates and risk of life-threatening complications is lower. However, cases of a serious disease called post-infectious multisystem inflammatory syndrome in children (MIS-C), which can be fatal, have been described. In severe cases of COVID-19, endothelial damage develops as a result of an aggressive immune response. As a result of endothelial damage, coagulation factors increase. The respiratory distress of patients is supposed to be mainly due to endothelial damage. Endothelial activation and dysfunction have a critical role in the serious complications of COVID-19. Asymmetric dimethylarginine (ADMA) is an arginine-like substance synthesized in endothelial cells and found in human urine, plasma and tissues. ADMA, an endogenous inhibitor of nitric oxide synthase (NOS), causes disruption of endothelium-dependent vasodilation by reducing nitric oxide (NO) synthesis. When we reviewed the literature, we could not find any study on the relationship of ADMA with MIS-C disease and COVID-19 in children. In our study, we aimed to investigate whether the serum level of ADMA, a biomarker of endothelial dysfunction, can be used to predict prognosis and clinical course in COVID-19 and MIS-C diseases in which endothelial damage is effective in their pathogenesis. The study group included 98 patients diagnosed with COVID-19 and 21 patients diagnosed with MIS-C who admitted between June 2021 and January 2022, to our pediatric emergency clinic. The control group consisted of forty two people. Patients diagnosed with COVID-19 were divided into three groups as; outpatients, hospitalized patients in pediatric infectious disease department and those in need of intensive care. Patients diagnosed with MIS-C, were evaluated as a separate group. The median ADMA levels of the outpatient COVID-19 group, hospitalized COVID-19 group, COVID-19 patients followed up the intensive care unit, and MIS-C group were 8097.0 ng/L, 13195.6 ng/L, 19361.4 ng/L, 15735.5 ng/L, respectively. Median ADMA levels of control group was 4081.0 ng/L. ADMA levels of COVID-19 patients hospitalized in the intensive care unit and MIS-C patients were significantly higher than the outpatients and COVID-19 patients hospitalized in pediatric infectious disease department (p<0.001). In addition, serum ADMA level was found to be significantly higher in all patient groups compared to the control group. In conclusion, our study is the first to investigate ADMA levels in children with COVID-19 and MIS-C. We found that ADMA levels were significantly higher in patients with MIS-C and COVID-19 patients who needed intensive care. We think that a serum ADMA level above 6135,15 ng/L can be used as a limit for demonstrating endothelial dysfunction. More comprehensive studies are needed to reach more precise judgments on this issue. Keywords: COVID-19, ADMA, endothelial damage, MIS-C, SARS-CoV-2