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Microvascular and proteomic signatures overlap in COVID-19 and bacterial sepsis: the MICROCODE study
AIMS: Although coronavirus disease 2019 (COVID-19) and bacterial sepsis are distinct conditions, both are known to trigger endothelial dysfunction with corresponding microcirculatory impairment. The purpose of this study was to compare microvascular injury patterns and proteomic signatures in COVID-...
Autores principales: | , , , , , , , , , , , , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
Springer Netherlands
2022
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9208353/ https://www.ncbi.nlm.nih.gov/pubmed/35723762 http://dx.doi.org/10.1007/s10456-022-09843-8 |
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author | Rovas, Alexandros Buscher, Konrad Osiaevi, Irina Drost, Carolin Christina Sackarnd, Jan Tepasse, Phil-Robin Fobker, Manfred Kühn, Joachim Braune, Stephan Göbel, Ulrich Thölking, Gerold Gröschel, Andreas Rossaint, Jan Vink, Hans Lukasz, Alexander Pavenstädt, Hermann Kümpers, Philipp |
author_facet | Rovas, Alexandros Buscher, Konrad Osiaevi, Irina Drost, Carolin Christina Sackarnd, Jan Tepasse, Phil-Robin Fobker, Manfred Kühn, Joachim Braune, Stephan Göbel, Ulrich Thölking, Gerold Gröschel, Andreas Rossaint, Jan Vink, Hans Lukasz, Alexander Pavenstädt, Hermann Kümpers, Philipp |
author_sort | Rovas, Alexandros |
collection | PubMed |
description | AIMS: Although coronavirus disease 2019 (COVID-19) and bacterial sepsis are distinct conditions, both are known to trigger endothelial dysfunction with corresponding microcirculatory impairment. The purpose of this study was to compare microvascular injury patterns and proteomic signatures in COVID-19 and bacterial sepsis patients. METHODS AND RESULTS: This multi-center, observational study included 22 hospitalized adult COVID-19 patients, 43 hospitalized bacterial sepsis patients, and 10 healthy controls from 4 hospitals. Microcirculation and glycocalyx dimensions were quantified via intravital sublingual microscopy. Plasma proteins were measured using targeted proteomics (Olink). Coregulation and cluster analysis of plasma proteins was performed using a training-set and confirmed in a test-set. An independent external cohort of 219 COVID-19 patients was used for validation and outcome analysis. Microcirculation and plasma proteome analysis found substantial overlap between COVID-19 and bacterial sepsis. Severity, but not disease entity explained most data variation. Unsupervised correlation analysis identified two main coregulated plasma protein signatures in both diseases that strictly counteract each other. They were associated with microvascular dysfunction and several established markers of clinical severity. The signatures were used to derive new composite biomarkers of microvascular injury that allow to predict 28-day mortality or/and intubation (area under the curve 0.90, p < 0.0001) in COVID-19. CONCLUSION: Our data imply a common biological host response of microvascular injury in both bacterial sepsis and COVID-19. A distinct plasma signature correlates with endothelial health and improved outcomes, while a counteracting response is associated with glycocalyx breakdown and high mortality. Microvascular health biomarkers are powerful predictors of clinical outcomes. GRAPHICAL ABSTRACT: [Image: see text] SUPPLEMENTARY INFORMATION: The online version contains supplementary material available at 10.1007/s10456-022-09843-8. |
format | Online Article Text |
id | pubmed-9208353 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2022 |
publisher | Springer Netherlands |
record_format | MEDLINE/PubMed |
spelling | pubmed-92083532022-06-21 Microvascular and proteomic signatures overlap in COVID-19 and bacterial sepsis: the MICROCODE study Rovas, Alexandros Buscher, Konrad Osiaevi, Irina Drost, Carolin Christina Sackarnd, Jan Tepasse, Phil-Robin Fobker, Manfred Kühn, Joachim Braune, Stephan Göbel, Ulrich Thölking, Gerold Gröschel, Andreas Rossaint, Jan Vink, Hans Lukasz, Alexander Pavenstädt, Hermann Kümpers, Philipp Angiogenesis Original Paper AIMS: Although coronavirus disease 2019 (COVID-19) and bacterial sepsis are distinct conditions, both are known to trigger endothelial dysfunction with corresponding microcirculatory impairment. The purpose of this study was to compare microvascular injury patterns and proteomic signatures in COVID-19 and bacterial sepsis patients. METHODS AND RESULTS: This multi-center, observational study included 22 hospitalized adult COVID-19 patients, 43 hospitalized bacterial sepsis patients, and 10 healthy controls from 4 hospitals. Microcirculation and glycocalyx dimensions were quantified via intravital sublingual microscopy. Plasma proteins were measured using targeted proteomics (Olink). Coregulation and cluster analysis of plasma proteins was performed using a training-set and confirmed in a test-set. An independent external cohort of 219 COVID-19 patients was used for validation and outcome analysis. Microcirculation and plasma proteome analysis found substantial overlap between COVID-19 and bacterial sepsis. Severity, but not disease entity explained most data variation. Unsupervised correlation analysis identified two main coregulated plasma protein signatures in both diseases that strictly counteract each other. They were associated with microvascular dysfunction and several established markers of clinical severity. The signatures were used to derive new composite biomarkers of microvascular injury that allow to predict 28-day mortality or/and intubation (area under the curve 0.90, p < 0.0001) in COVID-19. CONCLUSION: Our data imply a common biological host response of microvascular injury in both bacterial sepsis and COVID-19. A distinct plasma signature correlates with endothelial health and improved outcomes, while a counteracting response is associated with glycocalyx breakdown and high mortality. Microvascular health biomarkers are powerful predictors of clinical outcomes. GRAPHICAL ABSTRACT: [Image: see text] SUPPLEMENTARY INFORMATION: The online version contains supplementary material available at 10.1007/s10456-022-09843-8. Springer Netherlands 2022-06-20 2022 /pmc/articles/PMC9208353/ /pubmed/35723762 http://dx.doi.org/10.1007/s10456-022-09843-8 Text en © The Author(s) 2022 https://creativecommons.org/licenses/by/4.0/Open AccessThis article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons licence, and indicate if changes were made. The images or other third party material in this article are included in the article's Creative Commons licence, unless indicated otherwise in a credit line to the material. If material is not included in the article's Creative Commons licence and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this licence, visit http://creativecommons.org/licenses/by/4.0/ (https://creativecommons.org/licenses/by/4.0/) . |
spellingShingle | Original Paper Rovas, Alexandros Buscher, Konrad Osiaevi, Irina Drost, Carolin Christina Sackarnd, Jan Tepasse, Phil-Robin Fobker, Manfred Kühn, Joachim Braune, Stephan Göbel, Ulrich Thölking, Gerold Gröschel, Andreas Rossaint, Jan Vink, Hans Lukasz, Alexander Pavenstädt, Hermann Kümpers, Philipp Microvascular and proteomic signatures overlap in COVID-19 and bacterial sepsis: the MICROCODE study |
title | Microvascular and proteomic signatures overlap in COVID-19 and bacterial sepsis: the MICROCODE study |
title_full | Microvascular and proteomic signatures overlap in COVID-19 and bacterial sepsis: the MICROCODE study |
title_fullStr | Microvascular and proteomic signatures overlap in COVID-19 and bacterial sepsis: the MICROCODE study |
title_full_unstemmed | Microvascular and proteomic signatures overlap in COVID-19 and bacterial sepsis: the MICROCODE study |
title_short | Microvascular and proteomic signatures overlap in COVID-19 and bacterial sepsis: the MICROCODE study |
title_sort | microvascular and proteomic signatures overlap in covid-19 and bacterial sepsis: the microcode study |
topic | Original Paper |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9208353/ https://www.ncbi.nlm.nih.gov/pubmed/35723762 http://dx.doi.org/10.1007/s10456-022-09843-8 |
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