TY - JOUR
T1 - Severe COVID-19 Is Characterised by Perturbations in Plasma Amines Correlated with Immune Response Markers, and Linked to Inflammation and Oxidative Stress
AU - Karu, Naama
AU - Kindt, Alida
AU - van Gammeren, Adriaan J.
AU - Ermens, Anton A.M.
AU - Harms, Amy C.
AU - Portengen, Lutzen
AU - Vermeulen, Roel C.H.
AU - Dik, Willem A.
AU - Langerak, Anton W.
AU - van der Velden, Vincent H.J.
AU - Hankemeier, Thomas
N1 - Funding Information:
Funding: The study was supported by the TKI-LSH project ‘METACOVID’ and by the NWA project ‘Measuring and detection of health’. The research is part of the Netherlands X-omics Initiative and partially funded by NWO, project 184.034.019.
Publisher Copyright:
© 2022 by the authors. Li-censee MDPI, Basel, Switzerland.
PY - 2022/7/2
Y1 - 2022/7/2
N2 - 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 con-valescing 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.
AB - 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 con-valescing 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.
UR - http://www.scopus.com/inward/record.url?scp=85133652901&partnerID=8YFLogxK
U2 - 10.3390/metabo12070618
DO - 10.3390/metabo12070618
M3 - Article
C2 - 35888742
AN - SCOPUS:85133652901
SN - 2218-1989
VL - 12
JO - Metabolites
JF - Metabolites
IS - 7
M1 - 618
ER -
