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Systemic complement activation is associated with respiratory failure in COVID-19 hospitalized patients
Respiratory failure in the acute respiratory syndrome coronavirus 2 (SARS-CoV-2) pandemic is hypothesized to be driven by an overreacting innate immune response, where the complement system is a key player. In this prospective cohort study of 39 hospitalized coronavirus disease COVID-19 patients, we...
Autores principales: | , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
National Academy of Sciences
2020
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7547220/ https://www.ncbi.nlm.nih.gov/pubmed/32943538 http://dx.doi.org/10.1073/pnas.2010540117 |
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author | Holter, Jan C. Pischke, Soeren E. de Boer, Eline Lind, Andreas Jenum, Synne Holten, Aleksander R. Tonby, Kristian Barratt-Due, Andreas Sokolova, Marina Schjalm, Camilla Chaban, Viktoriia Kolderup, Anette Tran, Trung Tollefsrud Gjølberg, Torleif Skeie, Linda G. Hesstvedt, Liv Ormåsen, Vidar Fevang, Børre Austad, Cathrine Müller, Karl Erik Fladeby, Cathrine Holberg-Petersen, Mona Halvorsen, Bente Müller, Fredrik Aukrust, Pål Dudman, Susanne Ueland, Thor Andersen, Jan Terje Lund-Johansen, Fridtjof Heggelund, Lars Dyrhol-Riise, Anne M. Mollnes, Tom E. |
author_facet | Holter, Jan C. Pischke, Soeren E. de Boer, Eline Lind, Andreas Jenum, Synne Holten, Aleksander R. Tonby, Kristian Barratt-Due, Andreas Sokolova, Marina Schjalm, Camilla Chaban, Viktoriia Kolderup, Anette Tran, Trung Tollefsrud Gjølberg, Torleif Skeie, Linda G. Hesstvedt, Liv Ormåsen, Vidar Fevang, Børre Austad, Cathrine Müller, Karl Erik Fladeby, Cathrine Holberg-Petersen, Mona Halvorsen, Bente Müller, Fredrik Aukrust, Pål Dudman, Susanne Ueland, Thor Andersen, Jan Terje Lund-Johansen, Fridtjof Heggelund, Lars Dyrhol-Riise, Anne M. Mollnes, Tom E. |
author_sort | Holter, Jan C. |
collection | PubMed |
description | Respiratory failure in the acute respiratory syndrome coronavirus 2 (SARS-CoV-2) pandemic is hypothesized to be driven by an overreacting innate immune response, where the complement system is a key player. In this prospective cohort study of 39 hospitalized coronavirus disease COVID-19 patients, we describe systemic complement activation and its association with development of respiratory failure. Clinical data and biological samples were obtained at admission, days 3 to 5, and days 7 to 10. Respiratory failure was defined as PO(2)/FiO(2) ratio of ≤40 kPa. Complement activation products covering the classical/lectin (C4d), alternative (C3bBbP) and common pathway (C3bc, C5a, and sC5b-9), the lectin pathway recognition molecule MBL, and antibody serology were analyzed by enzyme-immunoassays; viral load by PCR. Controls comprised healthy blood donors. Consistently increased systemic complement activation was observed in the majority of COVID-19 patients during hospital stay. At admission, sC5b-9 and C4d were significantly higher in patients with than without respiratory failure (P = 0.008 and P = 0.034). Logistic regression showed increasing odds of respiratory failure with sC5b-9 (odds ratio 31.9, 95% CI 1.4 to 746, P = 0.03) and need for oxygen therapy with C4d (11.7, 1.1 to 130, P = 0.045). Admission sC5b-9 and C4d correlated significantly to ferritin (r = 0.64, P < 0.001; r = 0.69, P < 0.001). C4d, sC5b-9, and C5a correlated with antiviral antibodies, but not with viral load. Systemic complement activation is associated with respiratory failure in COVID-19 patients and provides a rationale for investigating complement inhibitors in future clinical trials. |
format | Online Article Text |
id | pubmed-7547220 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2020 |
publisher | National Academy of Sciences |
record_format | MEDLINE/PubMed |
spelling | pubmed-75472202020-10-22 Systemic complement activation is associated with respiratory failure in COVID-19 hospitalized patients Holter, Jan C. Pischke, Soeren E. de Boer, Eline Lind, Andreas Jenum, Synne Holten, Aleksander R. Tonby, Kristian Barratt-Due, Andreas Sokolova, Marina Schjalm, Camilla Chaban, Viktoriia Kolderup, Anette Tran, Trung Tollefsrud Gjølberg, Torleif Skeie, Linda G. Hesstvedt, Liv Ormåsen, Vidar Fevang, Børre Austad, Cathrine Müller, Karl Erik Fladeby, Cathrine Holberg-Petersen, Mona Halvorsen, Bente Müller, Fredrik Aukrust, Pål Dudman, Susanne Ueland, Thor Andersen, Jan Terje Lund-Johansen, Fridtjof Heggelund, Lars Dyrhol-Riise, Anne M. Mollnes, Tom E. Proc Natl Acad Sci U S A Biological Sciences Respiratory failure in the acute respiratory syndrome coronavirus 2 (SARS-CoV-2) pandemic is hypothesized to be driven by an overreacting innate immune response, where the complement system is a key player. In this prospective cohort study of 39 hospitalized coronavirus disease COVID-19 patients, we describe systemic complement activation and its association with development of respiratory failure. Clinical data and biological samples were obtained at admission, days 3 to 5, and days 7 to 10. Respiratory failure was defined as PO(2)/FiO(2) ratio of ≤40 kPa. Complement activation products covering the classical/lectin (C4d), alternative (C3bBbP) and common pathway (C3bc, C5a, and sC5b-9), the lectin pathway recognition molecule MBL, and antibody serology were analyzed by enzyme-immunoassays; viral load by PCR. Controls comprised healthy blood donors. Consistently increased systemic complement activation was observed in the majority of COVID-19 patients during hospital stay. At admission, sC5b-9 and C4d were significantly higher in patients with than without respiratory failure (P = 0.008 and P = 0.034). Logistic regression showed increasing odds of respiratory failure with sC5b-9 (odds ratio 31.9, 95% CI 1.4 to 746, P = 0.03) and need for oxygen therapy with C4d (11.7, 1.1 to 130, P = 0.045). Admission sC5b-9 and C4d correlated significantly to ferritin (r = 0.64, P < 0.001; r = 0.69, P < 0.001). C4d, sC5b-9, and C5a correlated with antiviral antibodies, but not with viral load. Systemic complement activation is associated with respiratory failure in COVID-19 patients and provides a rationale for investigating complement inhibitors in future clinical trials. National Academy of Sciences 2020-10-06 2020-09-17 /pmc/articles/PMC7547220/ /pubmed/32943538 http://dx.doi.org/10.1073/pnas.2010540117 Text en Copyright © 2020 the Author(s). Published by PNAS. http://creativecommons.org/licenses/by/4.0/ https://creativecommons.org/licenses/by/4.0/This open access article is distributed under Creative Commons Attribution License 4.0 (CC BY) (http://creativecommons.org/licenses/by/4.0/) . |
spellingShingle | Biological Sciences Holter, Jan C. Pischke, Soeren E. de Boer, Eline Lind, Andreas Jenum, Synne Holten, Aleksander R. Tonby, Kristian Barratt-Due, Andreas Sokolova, Marina Schjalm, Camilla Chaban, Viktoriia Kolderup, Anette Tran, Trung Tollefsrud Gjølberg, Torleif Skeie, Linda G. Hesstvedt, Liv Ormåsen, Vidar Fevang, Børre Austad, Cathrine Müller, Karl Erik Fladeby, Cathrine Holberg-Petersen, Mona Halvorsen, Bente Müller, Fredrik Aukrust, Pål Dudman, Susanne Ueland, Thor Andersen, Jan Terje Lund-Johansen, Fridtjof Heggelund, Lars Dyrhol-Riise, Anne M. Mollnes, Tom E. Systemic complement activation is associated with respiratory failure in COVID-19 hospitalized patients |
title | Systemic complement activation is associated with respiratory failure in COVID-19 hospitalized patients |
title_full | Systemic complement activation is associated with respiratory failure in COVID-19 hospitalized patients |
title_fullStr | Systemic complement activation is associated with respiratory failure in COVID-19 hospitalized patients |
title_full_unstemmed | Systemic complement activation is associated with respiratory failure in COVID-19 hospitalized patients |
title_short | Systemic complement activation is associated with respiratory failure in COVID-19 hospitalized patients |
title_sort | systemic complement activation is associated with respiratory failure in covid-19 hospitalized patients |
topic | Biological Sciences |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7547220/ https://www.ncbi.nlm.nih.gov/pubmed/32943538 http://dx.doi.org/10.1073/pnas.2010540117 |
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