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Differential Cytokine Responses in Hospitalized COVID-19 Patients Limit Efficacy of Remdesivir

A significant proportion of COVID-19 patients will progress to critical illness requiring invasive mechanical ventilation. This accentuates the need for a therapy that can reduce the severity of COVID-19. Clinical trials have shown the effectiveness of remdesivir in shortening recovery time and decr...

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Autores principales: Chan, Yi-Hao, Young, Barnaby E., Fong, Siew-Wai, Ding, Ying, Goh, Yun Shan, Chee, Rhonda Sin-Ling, Tan, Seow-Yen, Kalimuddin, Shirin, Tambyah, Paul A., Leo, Yee-Sin, Ng, Lisa F. P., Lye, David Chien, Renia, Laurent
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Frontiers Media S.A. 2021
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8275132/
https://www.ncbi.nlm.nih.gov/pubmed/34262564
http://dx.doi.org/10.3389/fimmu.2021.680188
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author Chan, Yi-Hao
Young, Barnaby E.
Fong, Siew-Wai
Ding, Ying
Goh, Yun Shan
Chee, Rhonda Sin-Ling
Tan, Seow-Yen
Kalimuddin, Shirin
Tambyah, Paul A.
Leo, Yee-Sin
Ng, Lisa F. P.
Lye, David Chien
Renia, Laurent
author_facet Chan, Yi-Hao
Young, Barnaby E.
Fong, Siew-Wai
Ding, Ying
Goh, Yun Shan
Chee, Rhonda Sin-Ling
Tan, Seow-Yen
Kalimuddin, Shirin
Tambyah, Paul A.
Leo, Yee-Sin
Ng, Lisa F. P.
Lye, David Chien
Renia, Laurent
author_sort Chan, Yi-Hao
collection PubMed
description A significant proportion of COVID-19 patients will progress to critical illness requiring invasive mechanical ventilation. This accentuates the need for a therapy that can reduce the severity of COVID-19. Clinical trials have shown the effectiveness of remdesivir in shortening recovery time and decreasing progression to respiratory failure and mechanical ventilation. However, some studies have highlighted its lack of efficacy in patients on high-flow oxygen and mechanical ventilation. This study uncovers some underlying immune response differences between responders and non-responders to remdesivir treatment. Immunological analyses revealed an upregulation of tissue repair factors BDNF, PDGF-BB and PIGF-1, as well as an increase in ratio of Th2-associated cytokine IL-4 to Th1-associated cytokine IFN-γ. Serological profiling of IgG subclasses corroborated this observation, with significantly higher magnitude of increase in Th2-associated IgG2 and IgG4 responses. These findings help to identify the mechanisms of immune regulation accompanying successful remdesivir treatment in severe COVID-19 patients.
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spelling pubmed-82751322021-07-13 Differential Cytokine Responses in Hospitalized COVID-19 Patients Limit Efficacy of Remdesivir Chan, Yi-Hao Young, Barnaby E. Fong, Siew-Wai Ding, Ying Goh, Yun Shan Chee, Rhonda Sin-Ling Tan, Seow-Yen Kalimuddin, Shirin Tambyah, Paul A. Leo, Yee-Sin Ng, Lisa F. P. Lye, David Chien Renia, Laurent Front Immunol Immunology A significant proportion of COVID-19 patients will progress to critical illness requiring invasive mechanical ventilation. This accentuates the need for a therapy that can reduce the severity of COVID-19. Clinical trials have shown the effectiveness of remdesivir in shortening recovery time and decreasing progression to respiratory failure and mechanical ventilation. However, some studies have highlighted its lack of efficacy in patients on high-flow oxygen and mechanical ventilation. This study uncovers some underlying immune response differences between responders and non-responders to remdesivir treatment. Immunological analyses revealed an upregulation of tissue repair factors BDNF, PDGF-BB and PIGF-1, as well as an increase in ratio of Th2-associated cytokine IL-4 to Th1-associated cytokine IFN-γ. Serological profiling of IgG subclasses corroborated this observation, with significantly higher magnitude of increase in Th2-associated IgG2 and IgG4 responses. These findings help to identify the mechanisms of immune regulation accompanying successful remdesivir treatment in severe COVID-19 patients. Frontiers Media S.A. 2021-06-28 /pmc/articles/PMC8275132/ /pubmed/34262564 http://dx.doi.org/10.3389/fimmu.2021.680188 Text en Copyright © 2021 Chan, Young, Fong, Ding, Goh, Chee, Tan, Kalimuddin, Tambyah, Leo, Ng, Lye and Renia 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
Chan, Yi-Hao
Young, Barnaby E.
Fong, Siew-Wai
Ding, Ying
Goh, Yun Shan
Chee, Rhonda Sin-Ling
Tan, Seow-Yen
Kalimuddin, Shirin
Tambyah, Paul A.
Leo, Yee-Sin
Ng, Lisa F. P.
Lye, David Chien
Renia, Laurent
Differential Cytokine Responses in Hospitalized COVID-19 Patients Limit Efficacy of Remdesivir
title Differential Cytokine Responses in Hospitalized COVID-19 Patients Limit Efficacy of Remdesivir
title_full Differential Cytokine Responses in Hospitalized COVID-19 Patients Limit Efficacy of Remdesivir
title_fullStr Differential Cytokine Responses in Hospitalized COVID-19 Patients Limit Efficacy of Remdesivir
title_full_unstemmed Differential Cytokine Responses in Hospitalized COVID-19 Patients Limit Efficacy of Remdesivir
title_short Differential Cytokine Responses in Hospitalized COVID-19 Patients Limit Efficacy of Remdesivir
title_sort differential cytokine responses in hospitalized covid-19 patients limit efficacy of remdesivir
topic Immunology
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8275132/
https://www.ncbi.nlm.nih.gov/pubmed/34262564
http://dx.doi.org/10.3389/fimmu.2021.680188
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