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Comparison of host endothelial, epithelial and inflammatory response in ICU patients with and without COVID-19: a prospective observational cohort study
BACKGROUND: Analyses of blood biomarkers involved in the host response to severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) viral infection can reveal distinct biological pathways and inform development and testing of therapeutics for COVID-19. Our objective was to evaluate host endotheli...
Autores principales: | , , , , , , , , , , , , , , , , , , , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
BioMed Central
2021
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8054255/ https://www.ncbi.nlm.nih.gov/pubmed/33874973 http://dx.doi.org/10.1186/s13054-021-03547-z |
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author | Bhatraju, Pavan K. Morrell, Eric D. Zelnick, Leila Sathe, Neha A. Chai, Xin-Ya Sakr, Sana S. Sahi, Sharon K. Sader, Anthony Lum, Dawn M. Liu, Ted Koetje, Neall Garay, Ashley Barnes, Elizabeth Lawson, Jonathan Cromer, Gail Bray, Mary K. Pipavath, Sudhakar Kestenbaum, Bryan R. Liles, W. Conrad Fink, Susan L. West, T. Eoin Evans, Laura Mikacenic, Carmen Wurfel, Mark M. |
author_facet | Bhatraju, Pavan K. Morrell, Eric D. Zelnick, Leila Sathe, Neha A. Chai, Xin-Ya Sakr, Sana S. Sahi, Sharon K. Sader, Anthony Lum, Dawn M. Liu, Ted Koetje, Neall Garay, Ashley Barnes, Elizabeth Lawson, Jonathan Cromer, Gail Bray, Mary K. Pipavath, Sudhakar Kestenbaum, Bryan R. Liles, W. Conrad Fink, Susan L. West, T. Eoin Evans, Laura Mikacenic, Carmen Wurfel, Mark M. |
author_sort | Bhatraju, Pavan K. |
collection | PubMed |
description | BACKGROUND: Analyses of blood biomarkers involved in the host response to severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) viral infection can reveal distinct biological pathways and inform development and testing of therapeutics for COVID-19. Our objective was to evaluate host endothelial, epithelial and inflammatory biomarkers in COVID-19. METHODS: We prospectively enrolled 171 ICU patients, including 78 (46%) patients positive and 93 (54%) negative for SARS-CoV-2 infection from April to September, 2020. We compared 22 plasma biomarkers in blood collected within 24 h and 3 days after ICU admission. RESULTS: In critically ill COVID-19 and non-COVID-19 patients, the most common ICU admission diagnoses were respiratory failure or pneumonia, followed by sepsis and other diagnoses. Similar proportions of patients in both groups received invasive mechanical ventilation at the time of study enrollment. COVID-19 and non-COVID-19 patients had similar rates of acute respiratory distress syndrome, severe acute kidney injury, and in-hospital mortality. While concentrations of interleukin 6 and 8 were not different between groups, markers of epithelial cell injury (soluble receptor for advanced glycation end products, sRAGE) and acute phase proteins (serum amyloid A, SAA) were significantly higher in COVID-19 compared to non-COVID-19, adjusting for demographics and APACHE III scores. In contrast, angiopoietin 2:1 (Ang-2:1 ratio) and soluble tumor necrosis factor receptor 1 (sTNFR-1), markers of endothelial dysfunction and inflammation, were significantly lower in COVID-19 (p < 0.002). Ang-2:1 ratio and SAA were associated with mortality only in non-COVID-19 patients. CONCLUSIONS: These studies demonstrate that, unlike other well-studied causes of critical illness, endothelial dysfunction may not be characteristic of severe COVID-19 early after ICU admission. Pathways resulting in elaboration of acute phase proteins and inducing epithelial cell injury may be promising targets for therapeutics in COVID-19. SUPPLEMENTARY INFORMATION: The online version contains supplementary material available at 10.1186/s13054-021-03547-z. |
format | Online Article Text |
id | pubmed-8054255 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2021 |
publisher | BioMed Central |
record_format | MEDLINE/PubMed |
spelling | pubmed-80542552021-04-19 Comparison of host endothelial, epithelial and inflammatory response in ICU patients with and without COVID-19: a prospective observational cohort study Bhatraju, Pavan K. Morrell, Eric D. Zelnick, Leila Sathe, Neha A. Chai, Xin-Ya Sakr, Sana S. Sahi, Sharon K. Sader, Anthony Lum, Dawn M. Liu, Ted Koetje, Neall Garay, Ashley Barnes, Elizabeth Lawson, Jonathan Cromer, Gail Bray, Mary K. Pipavath, Sudhakar Kestenbaum, Bryan R. Liles, W. Conrad Fink, Susan L. West, T. Eoin Evans, Laura Mikacenic, Carmen Wurfel, Mark M. Crit Care Research BACKGROUND: Analyses of blood biomarkers involved in the host response to severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) viral infection can reveal distinct biological pathways and inform development and testing of therapeutics for COVID-19. Our objective was to evaluate host endothelial, epithelial and inflammatory biomarkers in COVID-19. METHODS: We prospectively enrolled 171 ICU patients, including 78 (46%) patients positive and 93 (54%) negative for SARS-CoV-2 infection from April to September, 2020. We compared 22 plasma biomarkers in blood collected within 24 h and 3 days after ICU admission. RESULTS: In critically ill COVID-19 and non-COVID-19 patients, the most common ICU admission diagnoses were respiratory failure or pneumonia, followed by sepsis and other diagnoses. Similar proportions of patients in both groups received invasive mechanical ventilation at the time of study enrollment. COVID-19 and non-COVID-19 patients had similar rates of acute respiratory distress syndrome, severe acute kidney injury, and in-hospital mortality. While concentrations of interleukin 6 and 8 were not different between groups, markers of epithelial cell injury (soluble receptor for advanced glycation end products, sRAGE) and acute phase proteins (serum amyloid A, SAA) were significantly higher in COVID-19 compared to non-COVID-19, adjusting for demographics and APACHE III scores. In contrast, angiopoietin 2:1 (Ang-2:1 ratio) and soluble tumor necrosis factor receptor 1 (sTNFR-1), markers of endothelial dysfunction and inflammation, were significantly lower in COVID-19 (p < 0.002). Ang-2:1 ratio and SAA were associated with mortality only in non-COVID-19 patients. CONCLUSIONS: These studies demonstrate that, unlike other well-studied causes of critical illness, endothelial dysfunction may not be characteristic of severe COVID-19 early after ICU admission. Pathways resulting in elaboration of acute phase proteins and inducing epithelial cell injury may be promising targets for therapeutics in COVID-19. SUPPLEMENTARY INFORMATION: The online version contains supplementary material available at 10.1186/s13054-021-03547-z. BioMed Central 2021-04-19 /pmc/articles/PMC8054255/ /pubmed/33874973 http://dx.doi.org/10.1186/s13054-021-03547-z Text en © The Author(s) 2021 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/) . The Creative Commons Public Domain Dedication waiver (http://creativecommons.org/publicdomain/zero/1.0/ (https://creativecommons.org/publicdomain/zero/1.0/) ) applies to the data made available in this article, unless otherwise stated in a credit line to the data. |
spellingShingle | Research Bhatraju, Pavan K. Morrell, Eric D. Zelnick, Leila Sathe, Neha A. Chai, Xin-Ya Sakr, Sana S. Sahi, Sharon K. Sader, Anthony Lum, Dawn M. Liu, Ted Koetje, Neall Garay, Ashley Barnes, Elizabeth Lawson, Jonathan Cromer, Gail Bray, Mary K. Pipavath, Sudhakar Kestenbaum, Bryan R. Liles, W. Conrad Fink, Susan L. West, T. Eoin Evans, Laura Mikacenic, Carmen Wurfel, Mark M. Comparison of host endothelial, epithelial and inflammatory response in ICU patients with and without COVID-19: a prospective observational cohort study |
title | Comparison of host endothelial, epithelial and inflammatory response in ICU patients with and without COVID-19: a prospective observational cohort study |
title_full | Comparison of host endothelial, epithelial and inflammatory response in ICU patients with and without COVID-19: a prospective observational cohort study |
title_fullStr | Comparison of host endothelial, epithelial and inflammatory response in ICU patients with and without COVID-19: a prospective observational cohort study |
title_full_unstemmed | Comparison of host endothelial, epithelial and inflammatory response in ICU patients with and without COVID-19: a prospective observational cohort study |
title_short | Comparison of host endothelial, epithelial and inflammatory response in ICU patients with and without COVID-19: a prospective observational cohort study |
title_sort | comparison of host endothelial, epithelial and inflammatory response in icu patients with and without covid-19: a prospective observational cohort study |
topic | Research |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8054255/ https://www.ncbi.nlm.nih.gov/pubmed/33874973 http://dx.doi.org/10.1186/s13054-021-03547-z |
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