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Inferring molecular mechanisms of dexamethasone therapy in severe COVID-19 from existing transcriptomic data
Dexamethasone, a synthetic glucocorticoid, has previously shown mortality benefit in severe coronavirus disease 2019 (COVID-19) in a randomized controlled trial. As the illness is considered to reflect a hyperinflammatory state, this therapeutic effectiveness is presumably ascribed to broad anti-inf...
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Formato: | Online Artículo Texto |
Lenguaje: | English |
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Elsevier B.V.
2021
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Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8054526/ https://www.ncbi.nlm.nih.gov/pubmed/33887367 http://dx.doi.org/10.1016/j.gene.2021.145665 |
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author | Sharma, Abhay |
author_facet | Sharma, Abhay |
author_sort | Sharma, Abhay |
collection | PubMed |
description | Dexamethasone, a synthetic glucocorticoid, has previously shown mortality benefit in severe coronavirus disease 2019 (COVID-19) in a randomized controlled trial. As the illness is considered to reflect a hyperinflammatory state, this therapeutic effectiveness is presumably ascribed to broad anti-inflammatory activities of glucocorticoids. Here, an unbiased analysis of available transcriptomic data on lung and blood immune cells from severe COVID-19 patients and matching cellular models of dexamethasone treatment is presented that supports this presumption. Comparison of differentially expressed genes in severe COVID-19 with that in dexamethasone treated cells reveals a small set of genes that are regulated in opposite direction between the disease and the drug, and are enriched for genes and processes related to glucocorticoid pathway and receptor binding. This expression signature differentiates as a whole various cytokines from a set of anti-cytokine/anti-inflammatory agents, with the former resembling COVID-19 and the latter dexamethasone in gene regulation. The signature apparently relates to TNF- α, IL-1α, IL-1β, IFN-α, IFN-β, and IFN-γ signaling, but not IL-6 signaling, suggesting that therapeutic effect of dexamethasone in COVID-19 does not involve IL-6 pathway. However, as all these observations are purely based on bioinformatic analysis, experimental evidence will be required to validate the inferences drawn. In conclusion, the present analysis seems to provide a proof of concept for therapeutic mechanisms of dexamethasone in COVID-19. |
format | Online Article Text |
id | pubmed-8054526 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2021 |
publisher | Elsevier B.V. |
record_format | MEDLINE/PubMed |
spelling | pubmed-80545262021-04-19 Inferring molecular mechanisms of dexamethasone therapy in severe COVID-19 from existing transcriptomic data Sharma, Abhay Gene Short Communication Dexamethasone, a synthetic glucocorticoid, has previously shown mortality benefit in severe coronavirus disease 2019 (COVID-19) in a randomized controlled trial. As the illness is considered to reflect a hyperinflammatory state, this therapeutic effectiveness is presumably ascribed to broad anti-inflammatory activities of glucocorticoids. Here, an unbiased analysis of available transcriptomic data on lung and blood immune cells from severe COVID-19 patients and matching cellular models of dexamethasone treatment is presented that supports this presumption. Comparison of differentially expressed genes in severe COVID-19 with that in dexamethasone treated cells reveals a small set of genes that are regulated in opposite direction between the disease and the drug, and are enriched for genes and processes related to glucocorticoid pathway and receptor binding. This expression signature differentiates as a whole various cytokines from a set of anti-cytokine/anti-inflammatory agents, with the former resembling COVID-19 and the latter dexamethasone in gene regulation. The signature apparently relates to TNF- α, IL-1α, IL-1β, IFN-α, IFN-β, and IFN-γ signaling, but not IL-6 signaling, suggesting that therapeutic effect of dexamethasone in COVID-19 does not involve IL-6 pathway. However, as all these observations are purely based on bioinformatic analysis, experimental evidence will be required to validate the inferences drawn. In conclusion, the present analysis seems to provide a proof of concept for therapeutic mechanisms of dexamethasone in COVID-19. Elsevier B.V. 2021-07-01 2021-04-19 /pmc/articles/PMC8054526/ /pubmed/33887367 http://dx.doi.org/10.1016/j.gene.2021.145665 Text en © 2021 Elsevier B.V. All rights reserved. Since January 2020 Elsevier has created a COVID-19 resource centre with free information in English and Mandarin on the novel coronavirus COVID-19. The COVID-19 resource centre is hosted on Elsevier Connect, the company's public news and information website. Elsevier hereby grants permission to make all its COVID-19-related research that is available on the COVID-19 resource centre - including this research content - immediately available in PubMed Central and other publicly funded repositories, such as the WHO COVID database with rights for unrestricted research re-use and analyses in any form or by any means with acknowledgement of the original source. These permissions are granted for free by Elsevier for as long as the COVID-19 resource centre remains active. |
spellingShingle | Short Communication Sharma, Abhay Inferring molecular mechanisms of dexamethasone therapy in severe COVID-19 from existing transcriptomic data |
title | Inferring molecular mechanisms of dexamethasone therapy in severe COVID-19 from existing transcriptomic data |
title_full | Inferring molecular mechanisms of dexamethasone therapy in severe COVID-19 from existing transcriptomic data |
title_fullStr | Inferring molecular mechanisms of dexamethasone therapy in severe COVID-19 from existing transcriptomic data |
title_full_unstemmed | Inferring molecular mechanisms of dexamethasone therapy in severe COVID-19 from existing transcriptomic data |
title_short | Inferring molecular mechanisms of dexamethasone therapy in severe COVID-19 from existing transcriptomic data |
title_sort | inferring molecular mechanisms of dexamethasone therapy in severe covid-19 from existing transcriptomic data |
topic | Short Communication |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8054526/ https://www.ncbi.nlm.nih.gov/pubmed/33887367 http://dx.doi.org/10.1016/j.gene.2021.145665 |
work_keys_str_mv | AT sharmaabhay inferringmolecularmechanismsofdexamethasonetherapyinseverecovid19fromexistingtranscriptomicdata |