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Anti-C5a antibody vilobelimab treatment and the effect on biomarkers of inflammation and coagulation in patients with severe COVID-19: a substudy of the  phase 2 PANAMO trial

We recently reported in the phase 3 PANAMO trial that selectively blocking complement 5a (C5a) with vilobelimab led to improved survival in critically ill COVID-19 patients. C5a is an important contributor to the innate immune system and can also activate the coagulation system. High C5a levels have...

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Autores principales: Lim, Endry H. T., Vlaar, Alexander P. J., Bos, Lieuwe D. J., van Vught, Lonneke A., Boer, Anita M. Tuip-de, Dujardin, Romein W. G., Habel, Maria, Xu, Zhongli, Brouwer, Matthijs C., van de Beek, Diederik, de Bruin, Sanne
Formato: Online Artículo Texto
Lenguaje:English
Publicado: BioMed Central 2022
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9789513/
https://www.ncbi.nlm.nih.gov/pubmed/36566174
http://dx.doi.org/10.1186/s12931-022-02278-1
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author Lim, Endry H. T.
Vlaar, Alexander P. J.
Bos, Lieuwe D. J.
van Vught, Lonneke A.
Boer, Anita M. Tuip-de
Dujardin, Romein W. G.
Habel, Maria
Xu, Zhongli
Brouwer, Matthijs C.
van de Beek, Diederik
de Bruin, Sanne
author_facet Lim, Endry H. T.
Vlaar, Alexander P. J.
Bos, Lieuwe D. J.
van Vught, Lonneke A.
Boer, Anita M. Tuip-de
Dujardin, Romein W. G.
Habel, Maria
Xu, Zhongli
Brouwer, Matthijs C.
van de Beek, Diederik
de Bruin, Sanne
author_sort Lim, Endry H. T.
collection PubMed
description We recently reported in the phase 3 PANAMO trial that selectively blocking complement 5a (C5a) with vilobelimab led to improved survival in critically ill COVID-19 patients. C5a is an important contributor to the innate immune system and can also activate the coagulation system. High C5a levels have been reported in severely ill COVID-19 patients and correlate with disease severity and mortality. Previously, we assessed the potential benefit and safety of vilobelimab in severe COVID-19 patients. In the current substudy of the phase 2 PANAMO trial, we aim to explore the effects of vilobelimab on various biomarkers of inflammation and coagulation. Between March 31 and April 24, 2020, 17 patients with severe COVID-19 pneumonia were enrolled in an exploratory, open-label, randomised phase 2 trial. Blood markers of complement, endothelial activation, epithelial barrier disruption, inflammation, neutrophil activation, neutrophil extracellular trap (NET) formation and coagulopathy were measured using enzyme-linked immunosorbent assay (ELISA) or utilizing the Luminex platform. During the first 15 days after inclusion, change in biomarker concentrations between the two groups were modelled with linear mixed-effects models with spatial splines and compared. Eight patients were randomized to vilobelimab treatment plus best supportive care (BSC) and nine patients were randomized to BSC only. A significant decrease over time was seen in the vilobelimab plus BSC group for C5a compared to the BSC only group (p < 0.001). ADAMTS13 levels decreased over time in the BSC only group compared to the vilobelimab plus BSC group (p < 0.01) and interleukin-8 (IL-8) levels were statistically more suppressed in the vilobelimab plus BSC group compared to the BSC group (p = 0.03). Our preliminary results show that C5a inhibition decreases the inflammatory response and hypercoagulability, which likely explains the beneficial effect of vilobelimab in severe COVID-19 patients. Validation of these results in a larger sample size is warranted. SUPPLEMENTARY INFORMATION: The online version contains supplementary material available at 10.1186/s12931-022-02278-1.
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spelling pubmed-97895132022-12-25 Anti-C5a antibody vilobelimab treatment and the effect on biomarkers of inflammation and coagulation in patients with severe COVID-19: a substudy of the  phase 2 PANAMO trial Lim, Endry H. T. Vlaar, Alexander P. J. Bos, Lieuwe D. J. van Vught, Lonneke A. Boer, Anita M. Tuip-de Dujardin, Romein W. G. Habel, Maria Xu, Zhongli Brouwer, Matthijs C. van de Beek, Diederik de Bruin, Sanne Respir Res Correspondence We recently reported in the phase 3 PANAMO trial that selectively blocking complement 5a (C5a) with vilobelimab led to improved survival in critically ill COVID-19 patients. C5a is an important contributor to the innate immune system and can also activate the coagulation system. High C5a levels have been reported in severely ill COVID-19 patients and correlate with disease severity and mortality. Previously, we assessed the potential benefit and safety of vilobelimab in severe COVID-19 patients. In the current substudy of the phase 2 PANAMO trial, we aim to explore the effects of vilobelimab on various biomarkers of inflammation and coagulation. Between March 31 and April 24, 2020, 17 patients with severe COVID-19 pneumonia were enrolled in an exploratory, open-label, randomised phase 2 trial. Blood markers of complement, endothelial activation, epithelial barrier disruption, inflammation, neutrophil activation, neutrophil extracellular trap (NET) formation and coagulopathy were measured using enzyme-linked immunosorbent assay (ELISA) or utilizing the Luminex platform. During the first 15 days after inclusion, change in biomarker concentrations between the two groups were modelled with linear mixed-effects models with spatial splines and compared. Eight patients were randomized to vilobelimab treatment plus best supportive care (BSC) and nine patients were randomized to BSC only. A significant decrease over time was seen in the vilobelimab plus BSC group for C5a compared to the BSC only group (p < 0.001). ADAMTS13 levels decreased over time in the BSC only group compared to the vilobelimab plus BSC group (p < 0.01) and interleukin-8 (IL-8) levels were statistically more suppressed in the vilobelimab plus BSC group compared to the BSC group (p = 0.03). Our preliminary results show that C5a inhibition decreases the inflammatory response and hypercoagulability, which likely explains the beneficial effect of vilobelimab in severe COVID-19 patients. Validation of these results in a larger sample size is warranted. SUPPLEMENTARY INFORMATION: The online version contains supplementary material available at 10.1186/s12931-022-02278-1. BioMed Central 2022-12-24 2022 /pmc/articles/PMC9789513/ /pubmed/36566174 http://dx.doi.org/10.1186/s12931-022-02278-1 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/) . 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 Correspondence
Lim, Endry H. T.
Vlaar, Alexander P. J.
Bos, Lieuwe D. J.
van Vught, Lonneke A.
Boer, Anita M. Tuip-de
Dujardin, Romein W. G.
Habel, Maria
Xu, Zhongli
Brouwer, Matthijs C.
van de Beek, Diederik
de Bruin, Sanne
Anti-C5a antibody vilobelimab treatment and the effect on biomarkers of inflammation and coagulation in patients with severe COVID-19: a substudy of the  phase 2 PANAMO trial
title Anti-C5a antibody vilobelimab treatment and the effect on biomarkers of inflammation and coagulation in patients with severe COVID-19: a substudy of the  phase 2 PANAMO trial
title_full Anti-C5a antibody vilobelimab treatment and the effect on biomarkers of inflammation and coagulation in patients with severe COVID-19: a substudy of the  phase 2 PANAMO trial
title_fullStr Anti-C5a antibody vilobelimab treatment and the effect on biomarkers of inflammation and coagulation in patients with severe COVID-19: a substudy of the  phase 2 PANAMO trial
title_full_unstemmed Anti-C5a antibody vilobelimab treatment and the effect on biomarkers of inflammation and coagulation in patients with severe COVID-19: a substudy of the  phase 2 PANAMO trial
title_short Anti-C5a antibody vilobelimab treatment and the effect on biomarkers of inflammation and coagulation in patients with severe COVID-19: a substudy of the  phase 2 PANAMO trial
title_sort anti-c5a antibody vilobelimab treatment and the effect on biomarkers of inflammation and coagulation in patients with severe covid-19: a substudy of the  phase 2 panamo trial
topic Correspondence
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9789513/
https://www.ncbi.nlm.nih.gov/pubmed/36566174
http://dx.doi.org/10.1186/s12931-022-02278-1
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