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Theory and Practice of Glucocorticoids in COVID-19: Getting to the Heart of the Matter—A Critical Review and Viewpoints

Prolonged, low-dose glucocorticoids (GCs) have shown the highest efficacy among pharmacological and non-pharmacological treatments for COVID-19. Despite the World Health Organization’s recommendation against their use at the beginning of the pandemic, GCs at a dose equivalent to dexamethasone 6 mg/d...

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Autores principales: Salton, Francesco, Confalonieri, Paola, Meduri, Gianfranco Umberto, Mondini, Lucrezia, Trotta, Liliana, Barbieri, Mariangela, Bozzi, Chiara, Torregiani, Chiara, Lerda, Selene, Bellan, Mattia, Confalonieri, Marco, Ruaro, Barbara, Tavano, Stefano, Pozzan, Riccardo
Formato: Online Artículo Texto
Lenguaje:English
Publicado: MDPI 2023
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10385094/
https://www.ncbi.nlm.nih.gov/pubmed/37513836
http://dx.doi.org/10.3390/ph16070924
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author Salton, Francesco
Confalonieri, Paola
Meduri, Gianfranco Umberto
Mondini, Lucrezia
Trotta, Liliana
Barbieri, Mariangela
Bozzi, Chiara
Torregiani, Chiara
Lerda, Selene
Bellan, Mattia
Confalonieri, Marco
Ruaro, Barbara
Tavano, Stefano
Pozzan, Riccardo
author_facet Salton, Francesco
Confalonieri, Paola
Meduri, Gianfranco Umberto
Mondini, Lucrezia
Trotta, Liliana
Barbieri, Mariangela
Bozzi, Chiara
Torregiani, Chiara
Lerda, Selene
Bellan, Mattia
Confalonieri, Marco
Ruaro, Barbara
Tavano, Stefano
Pozzan, Riccardo
author_sort Salton, Francesco
collection PubMed
description Prolonged, low-dose glucocorticoids (GCs) have shown the highest efficacy among pharmacological and non-pharmacological treatments for COVID-19. Despite the World Health Organization’s recommendation against their use at the beginning of the pandemic, GCs at a dose equivalent to dexamethasone 6 mg/day for 10 days are now indicated in all COVID-19 cases who require respiratory support. However, the efficacy of the intervention depends on the timing of initiation, the dose, and other individual factors. Indeed, patients treated with similar GC protocols often experience different outcomes, which do not always correlate with the presence of comorbidities or with the severity of respiratory involvement at baseline. This prompted us to critically review the literature on the rationale, pharmacological principles, and clinical evidence that should guide GC treatment. Based on these data, the best treatment protocol probably involves an initial bolus dose to saturate the glucocorticoid receptors, followed by a continuous infusion to maintain constant plasma levels, and eventually a slow tapering to interruption. Methylprednisolone has shown the highest efficacy among different GC molecules, most likely thanks to its higher ability to penetrate the lung. Decreased tissue sensitivity to glucocorticoids is thought to be the main mechanism accounting for the lower response to the treatment in some individuals. We do not have a readily available test to identify GC resistance; therefore, to address inter-individual variability, future research should aim at investigating clinical, physiological, and laboratory markers to guide a personalized GC treatment approach.
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spelling pubmed-103850942023-07-30 Theory and Practice of Glucocorticoids in COVID-19: Getting to the Heart of the Matter—A Critical Review and Viewpoints Salton, Francesco Confalonieri, Paola Meduri, Gianfranco Umberto Mondini, Lucrezia Trotta, Liliana Barbieri, Mariangela Bozzi, Chiara Torregiani, Chiara Lerda, Selene Bellan, Mattia Confalonieri, Marco Ruaro, Barbara Tavano, Stefano Pozzan, Riccardo Pharmaceuticals (Basel) Review Prolonged, low-dose glucocorticoids (GCs) have shown the highest efficacy among pharmacological and non-pharmacological treatments for COVID-19. Despite the World Health Organization’s recommendation against their use at the beginning of the pandemic, GCs at a dose equivalent to dexamethasone 6 mg/day for 10 days are now indicated in all COVID-19 cases who require respiratory support. However, the efficacy of the intervention depends on the timing of initiation, the dose, and other individual factors. Indeed, patients treated with similar GC protocols often experience different outcomes, which do not always correlate with the presence of comorbidities or with the severity of respiratory involvement at baseline. This prompted us to critically review the literature on the rationale, pharmacological principles, and clinical evidence that should guide GC treatment. Based on these data, the best treatment protocol probably involves an initial bolus dose to saturate the glucocorticoid receptors, followed by a continuous infusion to maintain constant plasma levels, and eventually a slow tapering to interruption. Methylprednisolone has shown the highest efficacy among different GC molecules, most likely thanks to its higher ability to penetrate the lung. Decreased tissue sensitivity to glucocorticoids is thought to be the main mechanism accounting for the lower response to the treatment in some individuals. We do not have a readily available test to identify GC resistance; therefore, to address inter-individual variability, future research should aim at investigating clinical, physiological, and laboratory markers to guide a personalized GC treatment approach. MDPI 2023-06-25 /pmc/articles/PMC10385094/ /pubmed/37513836 http://dx.doi.org/10.3390/ph16070924 Text en © 2023 by the authors. https://creativecommons.org/licenses/by/4.0/Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license (https://creativecommons.org/licenses/by/4.0/).
spellingShingle Review
Salton, Francesco
Confalonieri, Paola
Meduri, Gianfranco Umberto
Mondini, Lucrezia
Trotta, Liliana
Barbieri, Mariangela
Bozzi, Chiara
Torregiani, Chiara
Lerda, Selene
Bellan, Mattia
Confalonieri, Marco
Ruaro, Barbara
Tavano, Stefano
Pozzan, Riccardo
Theory and Practice of Glucocorticoids in COVID-19: Getting to the Heart of the Matter—A Critical Review and Viewpoints
title Theory and Practice of Glucocorticoids in COVID-19: Getting to the Heart of the Matter—A Critical Review and Viewpoints
title_full Theory and Practice of Glucocorticoids in COVID-19: Getting to the Heart of the Matter—A Critical Review and Viewpoints
title_fullStr Theory and Practice of Glucocorticoids in COVID-19: Getting to the Heart of the Matter—A Critical Review and Viewpoints
title_full_unstemmed Theory and Practice of Glucocorticoids in COVID-19: Getting to the Heart of the Matter—A Critical Review and Viewpoints
title_short Theory and Practice of Glucocorticoids in COVID-19: Getting to the Heart of the Matter—A Critical Review and Viewpoints
title_sort theory and practice of glucocorticoids in covid-19: getting to the heart of the matter—a critical review and viewpoints
topic Review
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10385094/
https://www.ncbi.nlm.nih.gov/pubmed/37513836
http://dx.doi.org/10.3390/ph16070924
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