Maintained imbalance of triglycerides, apolipoproteins, energy metabolites and cytokines in long-term COVID-19 syndrome patients

Frontiers in Immunology

Immunology

Hartmut Schäfer¹  Claire Cannet¹  Helene Häberle²  Katharina Kienzle³  Siri Göpel³  Michael Bitzer⁴  Rosi Bissinger⁵  Anna Liu⁶  Yogesh Singh⁷  Georgy Berezhnoy⁸  Christoph Trautwein⁸ 

[1]Bruker BioSpin, Applied Industrial and Clinical Division, Ettlingen, Germany

[2]Department of Anesthesiology and Intensive Care Medicine, University Hospital Tübingen, Tübingen, Germany

[3]Department of Internal Medicine I, University Hospital Tübingen, Tübingen, Germany

[4]Department of Internal Medicine I, University Hospital Tübingen, Tübingen, Germany

[5]Center for Personalized Medicine, University Hospital Tübingen, Tubingen, Germany

[6]Division of Endocrinology, Diabetology and Nephrology, Department of Internal Medicine I, University Hospital Tübingen, Tübingen, Germany

[7]Research Institute of Women’s Health, University of Tübingen, Tübingen, Germany

[8]Research Institute of Women’s Health, University of Tübingen, Tübingen, Germany

[9]Institute of Medical Genetics and Applied Genomics, University of Tübingen, Tübingen, Germany

[10]Next Generation Sequencing (NGS) Competence Center Tübingen (NCCT), University of Tübingen, Tübingen, Germany

[11]Werner Siemens Imaging Center, Department of Preclinical Imaging and Radiopharmacy, University of Tübingen, Tübingen, Germany

关键词: long COVID-19;    Post-Acute COVID-19 syndrome (PACS);    NMR;    in-vitro diagnostics;    quantitative;    metabolomics;    lipoproteins;    inflammation;   

DOI  :  10.3389/fimmu.2023.1144224

 received in 2023-01-14, accepted in 2023-04-17,  发布年份 2023

来源: Frontiers

【 摘 要 】

BackgroundDeep metabolomic, proteomic and immunologic phenotyping of patients suffering from an infection with severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) have matched a wide diversity of clinical symptoms with potential biomarkers for coronavirus disease 2019 (COVID-19). Several studies have described the role of small as well as complex molecules such as metabolites, cytokines, chemokines and lipoproteins during infection and in recovered patients. In fact, after an acute SARS-CoV-2 viral infection almost 10-20% of patients experience persistent symptoms post 12 weeks of recovery defined as long-term COVID-19 syndrome (LTCS) or long post-acute COVID-19 syndrome (PACS). Emerging evidence revealed that a dysregulated immune system and persisting inflammation could be one of the key drivers of LTCS. However, how these biomolecules altogether govern pathophysiology is largely underexplored. Thus, a clear understanding of how these parameters within an integrated fashion could predict the disease course would help to stratify LTCS patients from acute COVID-19 or recovered patients. This could even allow to elucidation of a potential mechanistic role of these biomolecules during the disease course.MethodsThis study comprised subjects with acute COVID-19 (n=7; longitudinal), LTCS (n=33), Recov (n=12), and no history of positive testing (n=73). 1H-NMR-based metabolomics with IVDr standard operating procedures verified and phenotyped all blood samples by quantifying 38 metabolites and 112 lipoprotein properties. Univariate and multivariate statistics identified NMR-based and cytokine changes. ResultsHere, we report on an integrated analysis of serum/plasma by NMR spectroscopy and flow cytometry-based cytokines/chemokines quantification in LTCS patients. We identified that in LTCS patients lactate and pyruvate were significantly different from either healthy controls (HC) or acute COVID-19 patients. Subsequently, correlation analysis in LTCS group only among cytokines and amino acids revealed that histidine and glutamine were uniquely attributed mainly with pro-inflammatory cytokines. Of note, triglycerides and several lipoproteins (apolipoproteins Apo-A1 and A2) in LTCS patients demonstrate COVID-19-like alterations compared with HC. Interestingly, LTCS and acute COVID-19 samples were distinguished mostly by their phenylalanine, 3-hydroxybutyrate (3-HB) and glucose concentrations, illustrating an imbalanced energy metabolism. Most of the cytokines and chemokines were present at low levels in LTCS patients compared with HC except for IL-18 chemokine, which tended to be higher in LTCS patients.ConclusionThe identification of these persisting plasma metabolites, lipoprotein and inflammation alterations will help to better stratify LTCS patients from other diseases and could help to predict ongoing severity of LTCS patients.

【 授权许可】

Unknown   
Copyright © 2023 Berezhnoy, Bissinger, Liu, Cannet, Schäfer, Kienzle, Bitzer, Häberle, Göpel, Trautwein and Singh