Investigation of indoleamine 2,3-dioxygenase enzyme in sars-cov-2 infection according to disease severity

Abstract

The kynurenine pathway interacts with almost all immune responses through metabolites and enzymes in the pathway. The rate-limiting enzyme, indoleamine 2,3-dioxygenase (IDO), serves as a pivotal oxidoreductase in the initial step of the pathway, catalyzing the conversion of tryptophan to kynurenine and is implicated in the pathogenesis of various infectious diseases. The aim of this study was to investigate the serum concentrations of IDO-1, cytokine concentrations related to Th1-217 and hematological parameters of coronavirus disease-2019 (COVID-19) patients considering the severity of the disease (mild, moderate, severe). The IDO-1 serum levels were measured using the [LISA method for 130 patients and 91 healthy controls and subsequently compared.Two single nucleotide polymorphism (SNP) regions associated with inflammation in the IDO gene locus were screened. SNP analyses were performed using melting curve analysis. The IDO-1 intronic variant rs7820268 and the IDO-2 inactivating region rs4503083 SNPs of 40 coronavirus disease-2019 (COVID-19) patients were compared to 52 healthy controls. All results were statistically analyzed and compared. The IDO-1 serum concentrations were significantly lower in the patient group compared to the healthy control group (p< 0.0001). Additionally, the IDO-1 serum levels in the severe patient group were lower than those in the mild patient group (p= 0.026). IL-4, IL-6, IL-10, TNF-alpha serum levels were significantly higher whereas IFN-gamma was lower in the patient group. A negative correlation was found between IDO-1 and IL-6 levels (r=-0.3503, p= 0.0391). Significant differences were found in the values of lymphocytes, monocytes, neutrophils and acute phase reactants in the patient groups classified according to disease severity. As a result of SNP genotype analysis, the CC genotype for the rs7820268 IDO-1 region was found to be significantly higher in the COVID-19 patient group when compared with those of healthy controls (p= 0.0017). These data suggest that polymorphism in the IDO-1 rs7820268 SNP region may be associated with susceptibility to COVID-19.