Kynurenine serves as useful biomarker in acute, Long- and Post-COVID-19 diagnostics

Abstract

IntroductionIn patients with SARS-CoV-2, innate immunity is playing a central role, depicted by hyperinflammation and longer lasting inflammatory response. Reliable inflammatory markers that cover both acute and long-lasting COVID-19 monitoring are still lacking. Thus, we investigated one specific inflammatory marker involved as one key player of the immune system, kynurenine (Kyn), and its use for diagnosis/detection of the Long-/Post-COVID syndrome in comparison to currently used markers in both serum and saliva samples.Material and methodsThe study compromised in total 151 inpatients with a SARS-CoV-2 infection hospitalized between 03/2020 and 09/2021. The group NC (normal controls) included blood bank donors (n=302, 144f/158m, mean age 47.1 ± 18.3 years (range 18-75)). Two further groups were generated based on Group A (n=85, 27f/58m, mean age 63.1 ± 18.3 years (range 19-90), acute admission to the hospital) and Group B (n=66, 22f/44m, mean age 66.6 ± 17.6 years (range 17-90), admitted either for weaning or for rehabilitation period due to Long-COVID symptoms/syndrome). Plasma concentrations of Kyn, C-Reactive Protein (CRP) and interleukin-6 (IL-6) were measured on admission. In Group B we determined Kyn 4 weeks after the negative PCR-test. In a subset of patients (n=11) concentrations of Kyn and CRP were measured in sera and saliva two, three and four months after dismission. We identified 12 patients with Post-COVID symptoms >20 weeks with still significant elevated Kyn-levels.ResultsMean values for NC used as reference were 2.79 ± 0.61 µM, range 1.2-4.1 µM. On admission, patients showed significantly higher concentrations of Kyn compared to NC (p-values < 0.001). Kyn significantly correlated with IL-6 peak-values (r=0.411; p-values <0.001) and CRP (r=0.488, p-values<0.001). Kyn values in Group B (Long-/Post-COVID) showed still significant higher values (8.77 ± 1.72 µM, range 5.5-16.6 µM), whereas CRP values in Group B were in the normal range.ConclusionSerum and saliva Kyn are reflecting the acute and long-term pathophysiology of the SARS-CoV-2 disease concerning the innate immune response and thus may serve a useful biomarker for diagnosis and monitoring both Long- and Post-COVID syndrome and its therapy.

SARS-CoV-2 Altered Hemorheological and Hematological Parameters during One-Month Observation Period in Critically Ill COVID-19 Patients

“…Virus-driven inflammation as an explanation is in line with our approximately six-fold increased ferritin and nine-fold increased CRP levels compared to clinical reference values [ 20 , 21 ], indicating a severe pro-inflammatory status in aCOV. While CRP is an established marker for acute inflammation and severity in COVID-19 and other diseases [ 53 , 54 ], ferritin can also be regarded as an acute phase protein besides its main function of iron storing and releasing [ 55 ]. Whereas CRP is decreasing over time in aCOV, ferritin levels are still elevated at T30, suggesting that it can be regarded as a longer-lasting marker for disease progression [ 56 ], subsequently negatively affecting hemorheological properties [ 57 ].…”

Diagnostic, Prognostic and Mechanistic Biomarkers of COVID-19 Identified by Mass Spectrometric Metabolomics

“…Among these, glutamate was found to be dysregulated in longitudinal studies across various COVID-19 waves [ 44 ]. Tryptophan metabolism was also confirmed to be perturbed in several studies, and two immunosuppressive tryptophan metabolites, kynurenine and anthranilic acid, were found to be associated with disease severity [ 41 , 67 , 69 ]. Elevations in such tryptophan metabolites were also found in patients with long-COVID or with cancer [ 37 , 71 ].…”

“…It is interesting to note that elevations of kynurenate accompany clinical deterioration in male (but not female) COVID-19 patients [ 66 ]. α-hydroxylated amino acid increased with disease severity and was related to reduced oxygen saturation and clinical markers of lung damage [ 18 , 61 , 64 , 69 ]. In addition to these amino acid-focused studies, alterations in carbohydrate and energy metabolism, tricarboxylic acid cycle (TCA), purine metabolism (adenine, GMP, cysteine, urea), polyamines, and nicotinamide metabolites have been reported.…”

“…In addition to these amino acid-focused studies, alterations in carbohydrate and energy metabolism, tricarboxylic acid cycle (TCA), purine metabolism (adenine, GMP, cysteine, urea), polyamines, and nicotinamide metabolites have been reported. Thus, multiple glycerophospholipids, including phosphatidylethanolamines (PEs), lysophosphatidylethanolamines (LysoPE), sphingolipids, ceramides (Cer), and triglycerides (TG) or palmitic acid, were found to be altered in samples from severe COVID-19 patients [ 21 , 69 , 72 ]. Sphingosine-1-phosphate significantly increases during the recovery process [ 21 , 73 ].…”

COVID‐19‐associated liver injury: Adding fuel to the flame

“…Proinflammatory cytokines convert tryptophan to kynurenine, which is associated with IL-6 peaks during acute SARS-CoV-2 infection. [149][150][151] Typically, kynurenine pathway activation is associated with immunosuppression. 152 Blocking aryl hydrocarbon receptor (AhR) signaling reduces liver fibrosis, kynurenine activates AhR as a ligand in T cells and regulates tumor immunity.…”