Cargando…

Cytokine levels associated with favorable clinical outcome in the CAPSID randomized trial of convalescent plasma in patients with severe COVID-19

OBJECTIVES: To determine the profile of cytokines in patients with severe COVID-19 who were enrolled in a trial of COVID-19 convalescent plasma (CCP). METHODS: Patients were randomized to receive standard treatment and 3 CCP units or standard treatment alone (CAPSID trial, ClinicalTrials.gov NCT0443...

Descripción completa

Detalles Bibliográficos
Autores principales: Körper, Sixten, Schrezenmeier, Eva Vanessa, Rincon-Arevalo, Hector, Grüner, Beate, Zickler, Daniel, Weiss, Manfred, Wiesmann, Thomas, Zacharowski, Kai, Kalbhenn, Johannes, Bentz, Martin, Dollinger, Matthias M., Paul, Gregor, Lepper, Philipp M., Ernst, Lucas, Wulf, Hinnerk, Zinn, Sebastian, Appl, Thomas, Jahrsdörfer, Bernd, Rojewski, Markus, Lotfi, Ramin, Dörner, Thomas, Jungwirth, Bettina, Seifried, Erhard, Fürst, Daniel, Schrezenmeier, Hubert
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Frontiers Media S.A. 2022
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9582990/
https://www.ncbi.nlm.nih.gov/pubmed/36275695
http://dx.doi.org/10.3389/fimmu.2022.1008438
_version_ 1784812968529100800
author Körper, Sixten
Schrezenmeier, Eva Vanessa
Rincon-Arevalo, Hector
Grüner, Beate
Zickler, Daniel
Weiss, Manfred
Wiesmann, Thomas
Zacharowski, Kai
Kalbhenn, Johannes
Bentz, Martin
Dollinger, Matthias M.
Paul, Gregor
Lepper, Philipp M.
Ernst, Lucas
Wulf, Hinnerk
Zinn, Sebastian
Appl, Thomas
Jahrsdörfer, Bernd
Rojewski, Markus
Lotfi, Ramin
Dörner, Thomas
Jungwirth, Bettina
Seifried, Erhard
Fürst, Daniel
Schrezenmeier, Hubert
author_facet Körper, Sixten
Schrezenmeier, Eva Vanessa
Rincon-Arevalo, Hector
Grüner, Beate
Zickler, Daniel
Weiss, Manfred
Wiesmann, Thomas
Zacharowski, Kai
Kalbhenn, Johannes
Bentz, Martin
Dollinger, Matthias M.
Paul, Gregor
Lepper, Philipp M.
Ernst, Lucas
Wulf, Hinnerk
Zinn, Sebastian
Appl, Thomas
Jahrsdörfer, Bernd
Rojewski, Markus
Lotfi, Ramin
Dörner, Thomas
Jungwirth, Bettina
Seifried, Erhard
Fürst, Daniel
Schrezenmeier, Hubert
author_sort Körper, Sixten
collection PubMed
description OBJECTIVES: To determine the profile of cytokines in patients with severe COVID-19 who were enrolled in a trial of COVID-19 convalescent plasma (CCP). METHODS: Patients were randomized to receive standard treatment and 3 CCP units or standard treatment alone (CAPSID trial, ClinicalTrials.gov NCT04433910). The primary outcome was a dichotomous composite outcome (survival and no longer severe COVID-19 on day 21). Time to clinical improvement was a key secondary endpoint. The concentrations of 27 cytokines were measured (baseline, day 7). We analyzed the change and the correlation between serum cytokine levels over time in different subgroups and the prediction of outcome in receiver operating characteristics (ROC) analyses and in multivariate models. RESULTS: The majority of cytokines showed significant changes from baseline to day 7. Some were strongly correlated amongst each other (at baseline the cluster IL-1ß, IL-2, IL-6, IL-8, G-CSF, MIP-1α, the cluster PDGF-BB, RANTES or the cluster IL-4, IL-17, Eotaxin, bFGF, TNF-α). The correlation matrix substantially changed from baseline to day 7. The heatmaps of the absolute values of the correlation matrix indicated an association of CCP treatment and clinical outcome with the cytokine pattern. Low levels of IP-10, IFN-γ, MCP-1 and IL-1ß on day 0 were predictive of treatment success in a ROC analysis. In multivariate models, low levels of IL-1ß, IFN-γ and MCP-1 on day 0 were significantly associated with both treatment success and shorter time to clinical improvement. Low levels of IP-10, IL-1RA, IL-6, MCP-1 and IFN-γ on day 7 and high levels of IL-9, PDGF and RANTES on day 7 were predictive of treatment success in ROC analyses. Low levels of IP-10, MCP-1 and high levels of RANTES, on day 7 were associated with both treatment success and shorter time to clinical improvement in multivariate models. CONCLUSION: This analysis demonstrates a considerable dynamic of cytokines over time, which is influenced by both treatment and clinical course of COVID-19. Levels of IL-1ß and MCP-1 at baseline and MCP-1, IP-10 and RANTES on day 7 were associated with a favorable outcome across several endpoints. These cytokines should be included in future trials for further evaluation as predictive factors.
format Online
Article
Text
id pubmed-9582990
institution National Center for Biotechnology Information
language English
publishDate 2022
publisher Frontiers Media S.A.
record_format MEDLINE/PubMed
spelling pubmed-95829902022-10-21 Cytokine levels associated with favorable clinical outcome in the CAPSID randomized trial of convalescent plasma in patients with severe COVID-19 Körper, Sixten Schrezenmeier, Eva Vanessa Rincon-Arevalo, Hector Grüner, Beate Zickler, Daniel Weiss, Manfred Wiesmann, Thomas Zacharowski, Kai Kalbhenn, Johannes Bentz, Martin Dollinger, Matthias M. Paul, Gregor Lepper, Philipp M. Ernst, Lucas Wulf, Hinnerk Zinn, Sebastian Appl, Thomas Jahrsdörfer, Bernd Rojewski, Markus Lotfi, Ramin Dörner, Thomas Jungwirth, Bettina Seifried, Erhard Fürst, Daniel Schrezenmeier, Hubert Front Immunol Immunology OBJECTIVES: To determine the profile of cytokines in patients with severe COVID-19 who were enrolled in a trial of COVID-19 convalescent plasma (CCP). METHODS: Patients were randomized to receive standard treatment and 3 CCP units or standard treatment alone (CAPSID trial, ClinicalTrials.gov NCT04433910). The primary outcome was a dichotomous composite outcome (survival and no longer severe COVID-19 on day 21). Time to clinical improvement was a key secondary endpoint. The concentrations of 27 cytokines were measured (baseline, day 7). We analyzed the change and the correlation between serum cytokine levels over time in different subgroups and the prediction of outcome in receiver operating characteristics (ROC) analyses and in multivariate models. RESULTS: The majority of cytokines showed significant changes from baseline to day 7. Some were strongly correlated amongst each other (at baseline the cluster IL-1ß, IL-2, IL-6, IL-8, G-CSF, MIP-1α, the cluster PDGF-BB, RANTES or the cluster IL-4, IL-17, Eotaxin, bFGF, TNF-α). The correlation matrix substantially changed from baseline to day 7. The heatmaps of the absolute values of the correlation matrix indicated an association of CCP treatment and clinical outcome with the cytokine pattern. Low levels of IP-10, IFN-γ, MCP-1 and IL-1ß on day 0 were predictive of treatment success in a ROC analysis. In multivariate models, low levels of IL-1ß, IFN-γ and MCP-1 on day 0 were significantly associated with both treatment success and shorter time to clinical improvement. Low levels of IP-10, IL-1RA, IL-6, MCP-1 and IFN-γ on day 7 and high levels of IL-9, PDGF and RANTES on day 7 were predictive of treatment success in ROC analyses. Low levels of IP-10, MCP-1 and high levels of RANTES, on day 7 were associated with both treatment success and shorter time to clinical improvement in multivariate models. CONCLUSION: This analysis demonstrates a considerable dynamic of cytokines over time, which is influenced by both treatment and clinical course of COVID-19. Levels of IL-1ß and MCP-1 at baseline and MCP-1, IP-10 and RANTES on day 7 were associated with a favorable outcome across several endpoints. These cytokines should be included in future trials for further evaluation as predictive factors. Frontiers Media S.A. 2022-10-06 /pmc/articles/PMC9582990/ /pubmed/36275695 http://dx.doi.org/10.3389/fimmu.2022.1008438 Text en Copyright © 2022 Körper, Schrezenmeier, Rincon-Arevalo, Grüner, Zickler, Weiss, Wiesmann, Zacharowski, Kalbhenn, Bentz, Dollinger, Paul, Lepper, Ernst, Wulf, Zinn, Appl, Jahrsdörfer, Rojewski, Lotfi, Dörner, Jungwirth, Seifried, Fürst and Schrezenmeier https://creativecommons.org/licenses/by/4.0/This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) and the copyright owner(s) are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.
spellingShingle Immunology
Körper, Sixten
Schrezenmeier, Eva Vanessa
Rincon-Arevalo, Hector
Grüner, Beate
Zickler, Daniel
Weiss, Manfred
Wiesmann, Thomas
Zacharowski, Kai
Kalbhenn, Johannes
Bentz, Martin
Dollinger, Matthias M.
Paul, Gregor
Lepper, Philipp M.
Ernst, Lucas
Wulf, Hinnerk
Zinn, Sebastian
Appl, Thomas
Jahrsdörfer, Bernd
Rojewski, Markus
Lotfi, Ramin
Dörner, Thomas
Jungwirth, Bettina
Seifried, Erhard
Fürst, Daniel
Schrezenmeier, Hubert
Cytokine levels associated with favorable clinical outcome in the CAPSID randomized trial of convalescent plasma in patients with severe COVID-19
title Cytokine levels associated with favorable clinical outcome in the CAPSID randomized trial of convalescent plasma in patients with severe COVID-19
title_full Cytokine levels associated with favorable clinical outcome in the CAPSID randomized trial of convalescent plasma in patients with severe COVID-19
title_fullStr Cytokine levels associated with favorable clinical outcome in the CAPSID randomized trial of convalescent plasma in patients with severe COVID-19
title_full_unstemmed Cytokine levels associated with favorable clinical outcome in the CAPSID randomized trial of convalescent plasma in patients with severe COVID-19
title_short Cytokine levels associated with favorable clinical outcome in the CAPSID randomized trial of convalescent plasma in patients with severe COVID-19
title_sort cytokine levels associated with favorable clinical outcome in the capsid randomized trial of convalescent plasma in patients with severe covid-19
topic Immunology
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9582990/
https://www.ncbi.nlm.nih.gov/pubmed/36275695
http://dx.doi.org/10.3389/fimmu.2022.1008438
work_keys_str_mv AT korpersixten cytokinelevelsassociatedwithfavorableclinicaloutcomeinthecapsidrandomizedtrialofconvalescentplasmainpatientswithseverecovid19
AT schrezenmeierevavanessa cytokinelevelsassociatedwithfavorableclinicaloutcomeinthecapsidrandomizedtrialofconvalescentplasmainpatientswithseverecovid19
AT rinconarevalohector cytokinelevelsassociatedwithfavorableclinicaloutcomeinthecapsidrandomizedtrialofconvalescentplasmainpatientswithseverecovid19
AT grunerbeate cytokinelevelsassociatedwithfavorableclinicaloutcomeinthecapsidrandomizedtrialofconvalescentplasmainpatientswithseverecovid19
AT zicklerdaniel cytokinelevelsassociatedwithfavorableclinicaloutcomeinthecapsidrandomizedtrialofconvalescentplasmainpatientswithseverecovid19
AT weissmanfred cytokinelevelsassociatedwithfavorableclinicaloutcomeinthecapsidrandomizedtrialofconvalescentplasmainpatientswithseverecovid19
AT wiesmannthomas cytokinelevelsassociatedwithfavorableclinicaloutcomeinthecapsidrandomizedtrialofconvalescentplasmainpatientswithseverecovid19
AT zacharowskikai cytokinelevelsassociatedwithfavorableclinicaloutcomeinthecapsidrandomizedtrialofconvalescentplasmainpatientswithseverecovid19
AT kalbhennjohannes cytokinelevelsassociatedwithfavorableclinicaloutcomeinthecapsidrandomizedtrialofconvalescentplasmainpatientswithseverecovid19
AT bentzmartin cytokinelevelsassociatedwithfavorableclinicaloutcomeinthecapsidrandomizedtrialofconvalescentplasmainpatientswithseverecovid19
AT dollingermatthiasm cytokinelevelsassociatedwithfavorableclinicaloutcomeinthecapsidrandomizedtrialofconvalescentplasmainpatientswithseverecovid19
AT paulgregor cytokinelevelsassociatedwithfavorableclinicaloutcomeinthecapsidrandomizedtrialofconvalescentplasmainpatientswithseverecovid19
AT lepperphilippm cytokinelevelsassociatedwithfavorableclinicaloutcomeinthecapsidrandomizedtrialofconvalescentplasmainpatientswithseverecovid19
AT ernstlucas cytokinelevelsassociatedwithfavorableclinicaloutcomeinthecapsidrandomizedtrialofconvalescentplasmainpatientswithseverecovid19
AT wulfhinnerk cytokinelevelsassociatedwithfavorableclinicaloutcomeinthecapsidrandomizedtrialofconvalescentplasmainpatientswithseverecovid19
AT zinnsebastian cytokinelevelsassociatedwithfavorableclinicaloutcomeinthecapsidrandomizedtrialofconvalescentplasmainpatientswithseverecovid19
AT applthomas cytokinelevelsassociatedwithfavorableclinicaloutcomeinthecapsidrandomizedtrialofconvalescentplasmainpatientswithseverecovid19
AT jahrsdorferbernd cytokinelevelsassociatedwithfavorableclinicaloutcomeinthecapsidrandomizedtrialofconvalescentplasmainpatientswithseverecovid19
AT rojewskimarkus cytokinelevelsassociatedwithfavorableclinicaloutcomeinthecapsidrandomizedtrialofconvalescentplasmainpatientswithseverecovid19
AT lotfiramin cytokinelevelsassociatedwithfavorableclinicaloutcomeinthecapsidrandomizedtrialofconvalescentplasmainpatientswithseverecovid19
AT dornerthomas cytokinelevelsassociatedwithfavorableclinicaloutcomeinthecapsidrandomizedtrialofconvalescentplasmainpatientswithseverecovid19
AT jungwirthbettina cytokinelevelsassociatedwithfavorableclinicaloutcomeinthecapsidrandomizedtrialofconvalescentplasmainpatientswithseverecovid19
AT seifriederhard cytokinelevelsassociatedwithfavorableclinicaloutcomeinthecapsidrandomizedtrialofconvalescentplasmainpatientswithseverecovid19
AT furstdaniel cytokinelevelsassociatedwithfavorableclinicaloutcomeinthecapsidrandomizedtrialofconvalescentplasmainpatientswithseverecovid19
AT schrezenmeierhubert cytokinelevelsassociatedwithfavorableclinicaloutcomeinthecapsidrandomizedtrialofconvalescentplasmainpatientswithseverecovid19