Browsing by Author "Klovins, Jānis"

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    Amino acid metabolism is significantly altered at the time of admission in hospital for severe COVID-19 patients: findings from longitudinal targeted metabolomics analysis
    (2021-12-08) Ansone, Laura; Briviba, Monta; Silamikelis, Ivars; Terentjeva, Anna; Pērkons, Ingus; Birzniece, Līga; Rovīte, Vita; Rozentāle, Baiba; Vīksna, Ludmila; Koļesova, Oksana; Kļaviņš, Kristaps; Klovins, Jānis; Rīga Stradiņš University
    The heterogeneity in severity and outcome of COVID-19 cases points out the urgent need for early molecular characterization of patients followed by risk-stratified care. The main objective of this study was to evaluate the fluctuations of serum metabolomic profiles of COVID-19 patients with severe illness during the different disease stages in a longitudinal manner. We demonstrate a distinct metabolomic signature in serum samples of 32 hospitalized patients at the acute phase compared to the recovery period, suggesting the tryptophan (tryptophan, kynurenine, and 3-hydroxy-DL-kynurenine) and arginine (citrulline and ornithine) metabolism as contributing pathways in the immune response to SARS-CoV-2 with a potential link to the clinical severity of the disease. In addition, we suggest that glutamine deprivation may further result in inhibited M2 macrophage polarization as a complementary process, and highlight the contribution of phenylalanine and tyrosine in the molecular mechanisms underlying the severe course of the infection. In conclusion, our results provide several functional metabolic markers for disease progression and severe outcome with potential clinical application. IMPORTANCE Although the host defense mechanisms against SARS-CoV-2 infection are still poorly described, they are of central importance in shaping the course of the disease and the possible outcome. Metabolomic profiling may complement the lacking knowledge of the molecular mechanisms underlying clinical manifestations and pathogenesis of COVID-19. Moreover, early identification of metabolomics-based biomarker signatures is proved to serve as an effective approach for the prediction of disease outcome. Here we provide the list of metabolites describing the severe, acute phase of the infection and bring the evidence of crucial metabolic pathways linked to aggressive immune responses. Finally, we suggest metabolomic phenotyping as a promising method for developing personalized care strategies in COVID-19 patients.
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    Associations between TNF-α, IL-6 and IL-10 Promoter Polymorphisms and Mortality in Severe Sepsis
    (2012) Sabeļņikovs, Oļegs; Ņikitina-Zaķe, Liene; Krūmiņa, Angelika; Jaunberga, Zane; Klovins, Jānis; Vīksna, Ludmila; Bjertnaes, Lars J.; Kovalchuka, Lilija; Vanags, Indulis; Department of Anaesthesiology, Intensive Care and Clinical simulations; Department of Infectology
    Aims: To determine whether an association exists between TNF-α308 A/G,IL-6174G/C, and IL-10-1082 A/G promoter polymorphisms and the corresponding systemic cytokine concentrations and outcome in patients suffering from sepsis. Place and Duration of Study: The study was performed in the Intensive Care Unit (ICU) of Pauls Stradins Clinical University Hospital, Riga. Between 1 August 2006 and 31 July2008. Methodology: We enrolled 103 consecutive intensive care unit patients with sepsis into a prospective case control study. Blood samples were obtained for extraction of DNA amplifying regions of interest by means of polymerase chain reaction technique (PCR)using specific primers for TNF-α, IL-6andIL-10. Simultaneously, plasma cytokines and standard laboratory variables were determined during the first 24 h after the diagnosis. Presence of septic shock, sequential organ failure assessment score (SOFA),demographic data and clinical outcome was noticed P < 0.05 was considered as statistically significant. Results: Non-survivors had significantly higher concentrations of TNF-α, IL-6 and IL-10.The carriage of the IL-6-174C allele and IL-10-1082G allele were associated with a higher risk of mortality in patients with severe sepsis. Presence of the TNF-α-308 A allele did not influence mortality differently from those lacking this allele. Conclusion: The present study demonstrated an association of the IL-6-174 and the IL-10-1082 with increased mortality in patients suffering from severe sepsis. We found no direct association between the examined polymorphisms and the corresponding cytokine levels.