Severe COVID-19 Is Characterised by Perturbations in Plasma Amines Correlated with Immune Response Markers, and Linked to Inflammation and Oxidative Stress
Naama Karu,
Alida Kindt,
Adriaan J. van Gammeren,
Anton A. M. Ermens,
Amy C. Harms,
Lutzen Portengen,
Roel C. H. Vermeulen,
Willem A. Dik,
Anton W. Langerak,
Vincent H. J. van der Velden,
Thomas Hankemeier
Affiliations
Naama Karu
Metabolomics and Analytics Centre, Leiden Academic Centre for Drug Research, Leiden University, 2333 CC Leiden, The Netherlands
Alida Kindt
Metabolomics and Analytics Centre, Leiden Academic Centre for Drug Research, Leiden University, 2333 CC Leiden, The Netherlands
Adriaan J. van Gammeren
Department of Clinical Chemistry and Hematology, Amphia Hospital, 4818 CK Breda, The Netherlands
Anton A. M. Ermens
Department of Clinical Chemistry and Hematology, Amphia Hospital, 4818 CK Breda, The Netherlands
Amy C. Harms
Metabolomics and Analytics Centre, Leiden Academic Centre for Drug Research, Leiden University, 2333 CC Leiden, The Netherlands
Lutzen Portengen
Department of Population Health Sciences, Institute for Risk Assessment Sciences, University Utrecht, 3584 CK Utrecht, The Netherlands
Roel C. H. Vermeulen
Department of Population Health Sciences, Institute for Risk Assessment Sciences, University Utrecht, 3584 CK Utrecht, The Netherlands
Willem A. Dik
Laboratory Medical Immunology, Department of Immunology, Erasmus MC University Medical Center Rotterdam, 3015 GD Rotterdam, The Netherlands
Anton W. Langerak
Laboratory Medical Immunology, Department of Immunology, Erasmus MC University Medical Center Rotterdam, 3015 GD Rotterdam, The Netherlands
Vincent H. J. van der Velden
Laboratory Medical Immunology, Department of Immunology, Erasmus MC University Medical Center Rotterdam, 3015 GD Rotterdam, The Netherlands
Thomas Hankemeier
Metabolomics and Analytics Centre, Leiden Academic Centre for Drug Research, Leiden University, 2333 CC Leiden, The Netherlands
The COVID-19 pandemic raised a need to characterise the biochemical response to SARS-CoV-2 infection and find biological markers to identify therapeutic targets. In support of these aims, we applied a range of LC-MS platforms to analyse over 100 plasma samples from patients with varying COVID-19 severity and with detailed clinical information on inflammatory responses (>30 immune markers). The first publication in a series reports the results of quantitative LC-MS/MS profiling of 56 amino acids and derivatives. A comparison between samples taken from ICU and ward patients revealed a notable increase in ten post-translationally modified amino acids that correlated with markers indicative of an excessive immune response: TNF-alpha, neutrophils, markers for macrophage, and leukocyte activation. Severe patients also had increased kynurenine, positively correlated with CRP and cytokines that induce its production. ICU and ward patients with high IL-6 showed decreased levels of 22 immune-supporting and anti-oxidative amino acids and derivatives (e.g., glutathione, GABA). These negatively correlated with CRP and IL-6 and positively correlated with markers indicative of adaptive immune activation. Including corresponding alterations in convalescing ward patients, the overall metabolic picture of severe COVID-19 reflected enhanced metabolic demands to maintain cell proliferation and redox balance, alongside increased inflammation and oxidative stress.
