Neopterin and kynurenine in serum and urine as prognostic biomarkers in hospitalized patients with delta and omicron variant SARS-CoV-2 infection.

Currently, no biomarker or scoring system could clearly identify patients at risk of progression to a severe coronavirus disease (COVID)-19. Even in patients with known risk factors, the fulminant course cannot be predicted with certainty. Analysis of commonly determined clinical parameters (frailty score, age, or body mass index) together with routine biomarkers of host response (C-reactive protein and viral nucleocapsid protein) in combination with new biomarkers neopterin, kynurenine, and tryptophan, could aid in predicting the patient outcome. In 2021 and 2022, urine and serum samples were prospectively collected on 1st to 4th day after hospital admission in 108 consecutive COVID-19 patients hospitalized at the University Hospital Hradec Králové, Czech Republic. Delta and omicron virus variants were studied. Neopterin, kynurenine and tryptophan were determined by liquid chromatography. A significant correlation was observed between urinary and serum biomarker concentrations. Urinary and serum neopterin, kynurenine and kynurenine/tryptophan ratio were significantly (p≤0.05) higher in patients who subsequently needed oxygen therapy vs. patients without oxygen therapy. These parameters were also significantly increased in patients who died during the hospitalization compared to survivors. Complex equations have been derived using the investigated biomarkers and other clinical or laboratory parameters to predict the risk of subsequent oxygen therapy or death during hospitalization. Present data demonstrate that neopterin, kynurenine and kynurenine/tryptophan ratio in the serum or in the urine represent promising biomarkers in the management of COVID-19 that may help to guide important therapeutic decisions.

Krčmová LK ，Matoušová K ，Javorská L ，Šmahel P ，Skála M ，Koblížek V ，Škop J ，Turoňová D ，Gančarčíková M ，Melichar B ... -  《-》

Evaluation of inflammatory biomarkers and vitamins in hospitalized patients with SARS-CoV-2 infection and post-COVID syndrome.

Concentrations of neopterin, kynurenine and kynurenine/tryptophan ratios predict prognosis and the need for oxygen therapy in patients hospitalized for severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection. The aims of the present study were to evaluate the changes of these biomarkers early in the course of infection, the association with the prior coronavirus disease (COVID-19) vaccination and therapeutic administration of Anti-SARS-CoV-2 monoclonal antibodies, investigation of other potential biomarkers including neuropilin, 8-hydroxy-2-deoxyguanosine and 8-hydroxyguanosine in patients hospitalized with SARS-CoV-2 infection and an assessment of these biomarkers and vitamins A, E and D in patients with post-COVID syndrome. Urine and blood samples were obtained on the 1st to the 4th day and 4th to 7th day from 108 patients hospitalized with COVID-19. Chromatography tandem mass spectrometry methods were used to analyse neopterin, kynurenine, tryptophan, liposoluble vitamins, and DNA damage biomarkers. A statistically significant decrease of neopterin, kynurenine and kynurenine/tryptophan ratios was observed on after 4th to 7th day of hospitalization, and concentrations of these biomarkers were increased in patients with poor prognosis and subsequent post-COVID syndrome. The concentrations of remaining biomarker and vitamins were not associated with outcomes, although markedly decreased concentrations of vitamin A, E and D were noted. The concentrations of neopterin, kynurenine and kynurenine/tryptophan ratios decrease during the course of infection SARS-CoV-2 and are associated with the post-COVID syndrome. No other prognostic biomarkers were identified.

Krčmová LK ，Javorská L ，Matoušová K ，Šmahel P ，Skála M ，Kopecký M ，Suwanvecho C ，Přívratská N ，Turoňová D ，Melichar B ... -  《-》

Serum neopterin levels in relation to mild and severe COVID-19.

Robertson J ，Gostner JM ，Nilsson S ，Andersson LM ，Fuchs D ，Gisslen M ... -  《BMC INFECTIOUS DISEASES》

Serum Immune System Biomarkers Neopterin and Interleukin-10 Are Strongly Related to Tryptophan Metabolism in Healthy Young Adults.

Changes in tryptophan metabolism through the vitamin B-6-dependent kynurenine pathway have been linked to activation of the immune system. We hypothesized that blood concentrations of tryptophan and its catabolites were associated with biomarkers relevant to inflammatory processes in healthy noninflamed subjects. Healthy young adults (n = 737) aged 18-28 y without any known diseases or clinical evidence of inflammation provided blood samples for analysis of serum tryptophan/kynurenine metabolites, neopterin, C-reactive protein (CRP), and plasma pyridoxal 5'-phosphate (PLP) with LC-tandem mass spectrometry methodologies. A panel of cytokines was measured in serum by using high-sensitivity ELISA assays. Anthropometric and lifestyle data were collected by questionnaire. Multiple linear regression analysis to determine the effect of measured serum cytokine concentrations as predictors of tryptophan metabolites was performed on inverse normal-rank transformations of the data, adjusted for sex, body mass index, smoking, alcohol intake, and contraceptive use in women. Median serum CRP and neopterin concentrations were well below established clinical cutoffs for inflammation. We observed significant positive associations between serum interleukin-10 (IL-10) and serum kynurenine (P = 0.0002), the kynurenine-to-tryptophan ratio (KTR) (P = 0.003), 3-hydroxykynurenine (P = 0.01), and 3-hydroxyanthranilic acid (P = 0.04). Serum neopterin was positively associated with kynurenine, the KTR (both P < 0.0001), and anthranilic acid (P = 0.004), and was negatively associated with serum tryptophan (P = 0.01) and PLP (P < 0.0001). Serum tumor necrosis factor α was also negatively associated with tryptophan (P < 0.001). In healthy young adults with no apparent inflammatory conditions, serum tryptophan metabolites are significantly associated with key immune system biomarkers. The observed association between IL-10 and kynurenine is unexpected and suggests that kynurenine-linked mechanisms promoting negative regulation of inflammatory responses are associated with normal immune homeostasis.

Deac OM ，Mills JL ，Gardiner CM ，Shane B ，Quinn L ，Midttun Ø ，McCann A ，Meyer K ，Ueland PM ，Fan R ，Lu Z ，Brody LC ，Molloy AM ... -  《-》

Assessment of neopterin and indoleamine 2,3-dioxygenase activity in patients with seasonal influenza: A pilot study.

Seasonal influenza is an important cause of morbidity and mortality worldwide. Immune activation after stimulation with interferon-gamma leads to increased production of neopterin but also results in increased tryptophan catabolism through indoleamine 2,3-dioxygenase (IDO). Our pilot study determined neopterin serum levels and IDO activity in patients with influenza infection and investigated whether neopterin is linked to clinical outcome parameters (mortality ≤30 days, acute cardiac events (ACE) length of hospitalization, ICU admission). Neopterin concentrations were analyzed in serum samples of 40 patients with a confirmed diagnosis of influenza infection and in-hospital treatment for >24 hours. Data were compared to values of 100 healthy blood donors and 48 age-matched pneumonia patients. In a subgroup of 14 patients, tryptophan and kynurenine concentrations, as well as kynurenine-to-tryptophan ratio, were analyzed. In all influenza patients, neopterin concentrations were increased and significantly higher compared to those determined in patients with pneumonia and healthy controls. Positive correlations between the duration of hospitalization and neopterin were found. Significantly higher levels of kynurenine, kynurenine-to-tryptophan ratio, and lower levels of tryptophan were seen in influenza patients compared to healthy controls. Neopterin seems to be related to the course of the disease and could be a valuable biomarker to identify patients at an elevated risk of a worsened outcome; however, further prospective validation studies are needed to support the here presented preliminary results.

Pizzini A ，Kurz K ，Santifaller J ，Tschurtschenthaler C ，Theurl I ，Fuchs D ，Weiss G ，Bellmann-Weiler R ... -  《-》