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IL-6 modulation for COVID-19: the right patients at the right time?

The ongoing pandemic caused by the novel coronavirus SARS-CoV-2 has disrupted the global economy and strained healthcare systems to their limits. After the virus first emerged in late 2019, the first intervention that demonstrated significant reductions in mortality for severe COVID-19 in large-scal...

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Autores principales: Ascierto, Paolo Antonio, Fu, Binqing, Wei, Haiming
Formato: Online Artículo Texto
Lenguaje:English
Publicado: BMJ Publishing Group 2021
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8042594/
https://www.ncbi.nlm.nih.gov/pubmed/33837054
http://dx.doi.org/10.1136/jitc-2020-002285
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author Ascierto, Paolo Antonio
Fu, Binqing
Wei, Haiming
author_facet Ascierto, Paolo Antonio
Fu, Binqing
Wei, Haiming
author_sort Ascierto, Paolo Antonio
collection PubMed
description The ongoing pandemic caused by the novel coronavirus SARS-CoV-2 has disrupted the global economy and strained healthcare systems to their limits. After the virus first emerged in late 2019, the first intervention that demonstrated significant reductions in mortality for severe COVID-19 in large-scale trials was corticosteroids. Additional options that may reduce the burden on the healthcare system by reducing the number of patients requiring intensive care unit support are desperately needed, yet no therapy has conclusively established benefit in randomized studies for the management of moderate or mild cases of disease. Severe COVID-19 disease is characterized by a respiratory distress syndrome accompanied by elevated levels of several systemic cytokines, in a profile that shares several features with known inflammatory pathologies such as hemophagocytic lymphohistiocytosis and cytokine release syndrome secondary to chimeric antigen receptor (CAR) T cell therapy. Based on these observations, modulation of inflammatory cytokines, particularly interleukin (IL)-6, was proposed as a strategy to mitigate severe disease. Despite encouraging recoveries with anti-IL-6 agents, especially tocilizumab from single-arm studies, early randomized trials returned mixed results in terms of clinical benefit with these interventions. Later, larger trials such as RECOVERY and REMAP-CAP, however, are establishing anti-IL-6 in combination with steroids as a potential option for hypoxic patients with evidence of hyperinflammation. We propose that a positive feedback loop primarily mediated by macrophages and monocytes initiates the inflammatory cascade in severe COVID-19, and thus optimal benefit with anti-IL-6 therapies may require intervention during a finite window of opportunity at the outset of hyperinflammation but before fulminant disease causes irreversible tissue damage—as defined clinically by C reactive protein levels higher than 75 mg/L.
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spelling pubmed-80425942021-04-13 IL-6 modulation for COVID-19: the right patients at the right time? Ascierto, Paolo Antonio Fu, Binqing Wei, Haiming J Immunother Cancer Review The ongoing pandemic caused by the novel coronavirus SARS-CoV-2 has disrupted the global economy and strained healthcare systems to their limits. After the virus first emerged in late 2019, the first intervention that demonstrated significant reductions in mortality for severe COVID-19 in large-scale trials was corticosteroids. Additional options that may reduce the burden on the healthcare system by reducing the number of patients requiring intensive care unit support are desperately needed, yet no therapy has conclusively established benefit in randomized studies for the management of moderate or mild cases of disease. Severe COVID-19 disease is characterized by a respiratory distress syndrome accompanied by elevated levels of several systemic cytokines, in a profile that shares several features with known inflammatory pathologies such as hemophagocytic lymphohistiocytosis and cytokine release syndrome secondary to chimeric antigen receptor (CAR) T cell therapy. Based on these observations, modulation of inflammatory cytokines, particularly interleukin (IL)-6, was proposed as a strategy to mitigate severe disease. Despite encouraging recoveries with anti-IL-6 agents, especially tocilizumab from single-arm studies, early randomized trials returned mixed results in terms of clinical benefit with these interventions. Later, larger trials such as RECOVERY and REMAP-CAP, however, are establishing anti-IL-6 in combination with steroids as a potential option for hypoxic patients with evidence of hyperinflammation. We propose that a positive feedback loop primarily mediated by macrophages and monocytes initiates the inflammatory cascade in severe COVID-19, and thus optimal benefit with anti-IL-6 therapies may require intervention during a finite window of opportunity at the outset of hyperinflammation but before fulminant disease causes irreversible tissue damage—as defined clinically by C reactive protein levels higher than 75 mg/L. BMJ Publishing Group 2021-04-09 /pmc/articles/PMC8042594/ /pubmed/33837054 http://dx.doi.org/10.1136/jitc-2020-002285 Text en © Author(s) (or their employer(s)) 2021. Re-use permitted under CC BY-NC. No commercial re-use. See rights and permissions. Published by BMJ. https://creativecommons.org/licenses/by-nc/4.0/This is an open access article distributed in accordance with the Creative Commons Attribution Non Commercial (CC BY-NC 4.0) license, which permits others to distribute, remix, adapt, build upon this work non-commercially, and license their derivative works on different terms, provided the original work is properly cited, appropriate credit is given, any changes made indicated, and the use is non-commercial. See http://creativecommons.org/licenses/by-nc/4.0/ (https://creativecommons.org/licenses/by-nc/4.0/) .
spellingShingle Review
Ascierto, Paolo Antonio
Fu, Binqing
Wei, Haiming
IL-6 modulation for COVID-19: the right patients at the right time?
title IL-6 modulation for COVID-19: the right patients at the right time?
title_full IL-6 modulation for COVID-19: the right patients at the right time?
title_fullStr IL-6 modulation for COVID-19: the right patients at the right time?
title_full_unstemmed IL-6 modulation for COVID-19: the right patients at the right time?
title_short IL-6 modulation for COVID-19: the right patients at the right time?
title_sort il-6 modulation for covid-19: the right patients at the right time?
topic Review
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8042594/
https://www.ncbi.nlm.nih.gov/pubmed/33837054
http://dx.doi.org/10.1136/jitc-2020-002285
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