Kynurenine pathway in Coronavirus disease (COVID‐19): Potential role in prognosis

Abstract

Background It is known that inflammatory responses play an important role in the pathophysiology of COVID‐19. Aims In this study, we aimed to examine the role of kynurenine (KYN) metabolism on the severity of COVID‐19 disease AQ5. Materials & Methods Seventy COVID‐19 patients of varying severity and 30 controls were included in the study. In addition to the classical laboratory parameters, KYN, tryptophan (TRP), kynurenic acid (KYNA), 3 hydroxykynurenine (3OHKYN), quinolinic acid (QA), and picolinic acid (PA) were measured with mass spectrometry. Results TRP, KYN, KYN:TRP ratio, KYNA, 3OHKYN, PA, and QA results were found to be significantly different in COVID‐19 patients (p < 0.001 for all). The KYN:TRP ratio and PA of severe COVID‐19 patients was statistically higher than that of mild‐moderate COVID‐19 patients (p < 0.001 for all). When results were examined, statistically significant correlations with KYN:TRP ratio, IL‐6, ferritin, and procalcitonin were only found in COVID‐19 patients. ROC analysis indicated that highest AUC values were obtained by KYN:TRP ratio and PA (0.751 vs 0.742). In determining the severity of COVID‐19 disease, the odd ratios (and confidence intervals) of KYN:TRP ratio and PA levels that were adjusted according to age, gender, and comorbidity were determined to be 1.44 (1.1–1.87, p = 0.008) and 1.06 (1.02–1.11, p = 0.006), respectively. Discussion & Conclusion According to the results of this study, KYN metabolites play a role in the pathophysiology of COVID‐19, especially KYN:TRP ratio and PA could be markers for identification of severe COVID‐19 cases.

Increased levels of circulating neurotoxic metabolites in patients with mild Covid19

“…We found increases in several kynurenine pathway metabolites, such as KYN, QUIN, 3-HK and PIC, together with higher levels of IL-6. Additionally, the increased levels in QUIN/TRP, QUIN/KYN, QUIN/KYNA and KYN/TRP, further support a recent published study by Cihan and colleagues (23). Pro-inflammatory pathway proteins, along with metabolites from the kynurenine pathway were significantly increased in patients that presented with both COVID-19 and hypertension when compared to COVID-19 patients that were not hypertensive.…”

“…We found increases in several kynurenine pathway metabolites, such as KYN, QUIN, 3-HK and PIC, together with higher levels of IL-6. Additionally, the increased levels in QUIN/TRP, QUIN/KYN, QUIN/KYNA and KYN/TRP, further support a recent published study by Cihan and colleagues (23).…”

“…Cihan and colleagues analyzed kynurenine pathway metabolites and inflammatory cytokines and found a positive correlation between IL-6 and various metabolites from the kynurenine pathway (23). Our study supports a positive correlation between IL-6 and QUIN as well as between IL-6 and 3-HK.…”

“…Previous research demonstrated alterations in kynurenine pathway activity following infection (23)(24)(25). Therefore, we investigated alterations in kynurenine pathway metabolite levels.…”

Metabolic Profiling at COVID-19 Onset Shows Disease Severity and Sex-Specific Dysregulation

“…The L-kynurenine/L-tryptophan ratio has been extensively studied in inflammatory diseases since was introduced decades ago as an index of tryptophan breakdown ( 54 ). In the context of COVID-19 infection, this ratio has also been explored ( 9 , 13 , 15 ) as it is related to the inflammatory state in COVID-19, and can be used in treatment decision ( 55 ), with some studies describing an increase in the L-kynurenine/L-tryptophan ratio associated with COVID-19 severity ( 55 , 56 ), poor prognosis ( 57 , 58 ),) and mortality ( 58 – 60 ),,. Consistently with these studies, we observed an upregulation of L-kynurenine and downregulation of L-tryptophan in severe COVID-19 patients, indicating an elevated L-kynurenine/L-tryptophan ratio, which suggests a disease-associated hyperactivation of the indoleamine-pyrrole 2,3-dioxygenase (IDO) enzyme.…”