Biology subjects

Treutiger, C. J.

Publications and source records attributed to Treutiger, C. J..

3 recordsLinked to original sources

bioRxiv2025

Systemic Multi-Omics Analysis Reveals Interferon Response Heterogeneity and Links Lipid Metabolism to Immune Alterations in Severe COVID-19

The immune response to SARS-CoV-2 infection is highly heterogeneous, and interferon (IFN)-stimulated genes (ISGs) play a central but context-dependent role in antiviral defense and immune dysregulation. To investigate how ISG heterogeneity relates to immune and metabolic states, we performed an integrated analysis of whole-blood transcriptomics, plasma proteomics, metabolomics, and immune activation markers in hospitalized COVID-19 patients and COVID-negative healthy controls and covalescent individuals. Patients segregated into low (LIS), moderate (MIS), and high (HIS) ISG expression endotypes, largely independent of clinical severity. While high ISG expression was associated with systemic inflammation and innate immune activation, severe disease within the HIS endotype was characterized by marked metabolic perturbations, including depletion of tricarboxylic acid cycle intermediates and multiple lipid classes involved in membrane integrity and immunometabolic signaling. Plasma-transfer assays demonstrated that plasma from severe HIS patients impaired neutrophil and monocyte activation ex vivo, indicating functional attenuation of innate immune responses despite elevated ISG expression. These metabolic alterations correlated with reduced immune activation, supporting the existence of an interferon-associated immune-metabolic axis that constrains immune functionality in severe disease. Although type I IFN neutralization was detected in a subset of patients with IFN antigen reactivity, these samples did not account for ISG heterogeneity or disease severity. Together, these findings show that high ISG expression defines a transcriptional endotype permissive for inflammation but insufficient for effective immune function, highlighting the importance of immune-metabolic context in shaping COVID-19 disease outcomes.

immunology↗

bioRxiv2025

Immune-Coagulation Dynamics in Severe COVID-19: Insights from Autoantibody Profiling and Transcriptomics

Severe COVID-19 is characterized by immune dysregulation and coagulation abnormalities, leading to complications such as thromboembolism and multi-organ failure. This study explores the relationship between autoantibodies targeting coagulation-related factors and gene expression in severe COVID-19. Whole-blood transcriptomics revealed upregulation of coagulation-related genes, including VWF and Factor V, in severe patients compared to mild cases and healthy controls. Autoantibody profiling against seven coagulation-related proteins (ADAMTS13, Factor V, Protein S, SERPINC1, Apo-H, PROC1, and Prothrombin) showed reactivities below established positivity thresholds, but mean-fluorescent intensities were elevated numerically in severe (Protein S) and convalescent (SERPINC1) patients. Correlation analysis revealed trends of negative associations between autoantibody reactivities and coagulation gene expression in severe cases, suggesting a potential role for autoantibodies in modulating immune-coagulation interactions warranting further orthogonal validation. Furthermore, age-dependent increases in subthreshold autoantibody reactivities were observed in severe cases, highlighting the potential impact of immunosenescence on disease severity. These findings do not exclude the possibility that subthreshold autoantibodies may contribute indirectly to immune-coagulation dynamics in severe COVID-19 through mechanisms beyond direct transcriptional regulation. This study highlights the complexity of immune-coagulation interactions and provides foundation for future research into their biological and clinical relevance, particularly for identifying biomarkers and therapeutic targets in thromboinflammatory diseases.

immunology↗

bioRxiv2021

Implications of central carbon metabolism in SARS-CoV-2 replication and disease severity

Viruses hijack host metabolic pathways for their replicative advantage. Several observational trans-omics analyses associated carbon and amino acid metabolism in coronavirus disease 2019 (COVID-19) severity in patients but lacked mechanistic insights. In this study, using patient- derived multi-omics data and in vitro infection assays, we aimed to understand i) role of key metabolic pathways in severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) reproduction and ii) its association with disease severity. Our data suggests that monocytes are key to the altered immune response during COVID-19. COVID-19 infection was associated with increased plasma glutamate levels, while glucose and mannose levels were determinants of the disease severity. Monocytes showed altered expression pattern of carbohydrate and amino acid transporters, GLUT1 and xCT respectively in severe COVID-19. Furthermore, lung epithelial cells (Calu-3) showed a strong acute metabolic adaptation following infection in vitro by modulating central carbon metabolism. We found that glycolysis and glutaminolysis are essential for virus replication and blocking these metabolic pathways caused significant reduction in virus production. Taken together, our study highlights that the virus utilizes and re-wires pathways governing central carbon metabolism leading to metabolic toxicity. Thus, the host metabolic perturbation could be an attractive strategy to limit the viral replication and disease severity.

microbiology↗