Deciphering sepsis: transforming diagnosis and treatment through systems immunology
Sepsis is an abnormal, life-threatening response to infection that leads to (multi-)organ dysfunction and failure. It causes ~20% of deaths worldwide each year, and most deaths related to severe COVID-19 share various molecular features with sepsis. Current treatment approaches (antimicrobials and s...
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Frontiers Media S.A.
2025-01-01
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| Series: | Frontiers in Science |
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| Online Access: | https://www.frontiersin.org/articles/10.3389/fsci.2024.1469417/full |
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| author | Robert E. W. Hancock Andy An Claudia C. dos Santos Amy H. Y. Lee |
| author_facet | Robert E. W. Hancock Andy An Claudia C. dos Santos Amy H. Y. Lee |
| author_sort | Robert E. W. Hancock |
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| description | Sepsis is an abnormal, life-threatening response to infection that leads to (multi-)organ dysfunction and failure. It causes ~20% of deaths worldwide each year, and most deaths related to severe COVID-19 share various molecular features with sepsis. Current treatment approaches (antimicrobials and supportive care) do not address the complexity of sepsis or its mechanistic heterogeneity between and within patients over time. Systems immunology methods, including multiomics (notably RNA sequencing transcriptomics), machine learning, and network biology analysis, have the potential to transform the management paradigm toward precision approaches. Immune dysfunctions evident very early in sepsis drive the development of novel diagnostic gene expression signatures (e.g., cellular reprogramming) that could inform early therapy. Sepsis patients can now be categorized into “endotypes” based on unique immune dysfunction mechanisms corresponding to varying severity and mortality rates, raising the prospect of endotype-specific diagnostics and patient-specific immune-directed therapy. Longitudinal within-patient analyses can also reveal mechanisms (including epigenetics) that drive differential sepsis trajectories over time, enabling the prospect of disease stage-specific therapy during and after hospitalization, including for post-sepsis and long COVID syndromes. Achieving this transformation will require addressing barriers to systems immunology research, including its cost and resource-intensiveness, the relatively low volume of available data, and lack of suitable animal models; it will also require a change in the mindset of healthcare providers toward precision approaches. This should be prioritized in multistakeholder collaborations involving research communities, healthcare providers/systems, patients, and governments to reduce the current high disease burden from sepsis and to mitigate against future pandemics. |
| format | Article |
| id | doaj-art-d2f44add404945d4ab54bbc0008cbb52 |
| institution | Kabale University |
| issn | 2813-6330 |
| language | English |
| publishDate | 2025-01-01 |
| publisher | Frontiers Media S.A. |
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| series | Frontiers in Science |
| spelling | doaj-art-d2f44add404945d4ab54bbc0008cbb522025-01-30T10:03:22ZengFrontiers Media S.A.Frontiers in Science2813-63302025-01-01210.3389/fsci.2024.14694171469417Deciphering sepsis: transforming diagnosis and treatment through systems immunologyRobert E. W. Hancock0Andy An1Claudia C. dos Santos2Amy H. Y. Lee3Department of Microbiology and Immunology, University of British Columbia, Vancouver, BC, CanadaDepartment of Microbiology and Immunology, University of British Columbia, Vancouver, BC, CanadaKeenan Research Centre for Biomedical Science, Critical Care Medicine, St. Michael’s Hospital, University of Toronto, Toronto, ON, CanadaDepartment of Molecular Biology and Biochemistry, Simon Fraser University, Burnaby, BC, CanadaSepsis is an abnormal, life-threatening response to infection that leads to (multi-)organ dysfunction and failure. It causes ~20% of deaths worldwide each year, and most deaths related to severe COVID-19 share various molecular features with sepsis. Current treatment approaches (antimicrobials and supportive care) do not address the complexity of sepsis or its mechanistic heterogeneity between and within patients over time. Systems immunology methods, including multiomics (notably RNA sequencing transcriptomics), machine learning, and network biology analysis, have the potential to transform the management paradigm toward precision approaches. Immune dysfunctions evident very early in sepsis drive the development of novel diagnostic gene expression signatures (e.g., cellular reprogramming) that could inform early therapy. Sepsis patients can now be categorized into “endotypes” based on unique immune dysfunction mechanisms corresponding to varying severity and mortality rates, raising the prospect of endotype-specific diagnostics and patient-specific immune-directed therapy. Longitudinal within-patient analyses can also reveal mechanisms (including epigenetics) that drive differential sepsis trajectories over time, enabling the prospect of disease stage-specific therapy during and after hospitalization, including for post-sepsis and long COVID syndromes. Achieving this transformation will require addressing barriers to systems immunology research, including its cost and resource-intensiveness, the relatively low volume of available data, and lack of suitable animal models; it will also require a change in the mindset of healthcare providers toward precision approaches. This should be prioritized in multistakeholder collaborations involving research communities, healthcare providers/systems, patients, and governments to reduce the current high disease burden from sepsis and to mitigate against future pandemics.https://www.frontiersin.org/articles/10.3389/fsci.2024.1469417/fullsepsissystems immunologydiagnosticsendotypesRNA-Seqmultiomics |
| spellingShingle | Robert E. W. Hancock Andy An Claudia C. dos Santos Amy H. Y. Lee Deciphering sepsis: transforming diagnosis and treatment through systems immunology Frontiers in Science sepsis systems immunology diagnostics endotypes RNA-Seq multiomics |
| title | Deciphering sepsis: transforming diagnosis and treatment through systems immunology |
| title_full | Deciphering sepsis: transforming diagnosis and treatment through systems immunology |
| title_fullStr | Deciphering sepsis: transforming diagnosis and treatment through systems immunology |
| title_full_unstemmed | Deciphering sepsis: transforming diagnosis and treatment through systems immunology |
| title_short | Deciphering sepsis: transforming diagnosis and treatment through systems immunology |
| title_sort | deciphering sepsis transforming diagnosis and treatment through systems immunology |
| topic | sepsis systems immunology diagnostics endotypes RNA-Seq multiomics |
| url | https://www.frontiersin.org/articles/10.3389/fsci.2024.1469417/full |
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