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Dexamethasone for Severe COVID-19: How Does It Work at Cellular and Molecular Levels?
Kino, Tomoshige; Burd, Irina; Segars, James H.
  • Kino T; Laboratory of Molecular and Genomic Endocrinology, Sidra Medicine, Doha 26999, Qatar.
  • Burd I; Department of Gynecology and Obstetrics, Johns Hopkins University School of Medicine, Baltimore, MD 21205, USA.
  • Segars JH; Department of Gynecology and Obstetrics, Johns Hopkins University School of Medicine, Baltimore, MD 21205, USA.
Int J Mol Sci ; 22(13)2021 Jun 23.
Article in English | MEDLINE | ID: covidwho-1282517
ABSTRACT
The coronavirus disease 2019 (COVID-19) caused by infection of the severe respiratory syndrome coronavirus-2 (SARS-CoV-2) significantly impacted human society. Recently, the synthetic pure glucocorticoid dexamethasone was identified as an effective compound for treatment of severe COVID-19. However, glucocorticoids are generally harmful for infectious diseases, such as bacterial sepsis and severe influenza pneumonia, which can develop respiratory failure and systemic inflammation similar to COVID-19. This apparent inconsistency suggests the presence of pathologic mechanism(s) unique to COVID-19 that renders this steroid effective. We review plausible mechanisms and advance the hypothesis that SARS-CoV-2 infection is accompanied by infected cell-specific glucocorticoid insensitivity as reported for some other viruses. This alteration in local glucocorticoid actions interferes with undesired glucocorticoid to facilitate viral replication but does not affect desired anti-inflammatory properties in non-infected organs/tissues. We postulate that the virus coincidentally causes glucocorticoid insensitivity in the process of modulating host cell activities for promoting its replication in infected cells. We explore this tenet focusing on SARS-CoV-2-encoding proteins and potential molecular mechanisms supporting this hypothetical glucocorticoid insensitivity unique to COVID-19 but not characteristic of other life-threatening viral diseases, probably due to a difference in specific virally-encoded molecules and host cell activities modulated by them.
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Full text: Available Collection: International databases Database: MEDLINE Main subject: Antiviral Agents / Dexamethasone / COVID-19 Drug Treatment / Hypothalamo-Hypophyseal System / Inflammation Type of study: Prognostic study Limits: Humans Language: English Year: 2021 Document Type: Article Affiliation country: Ijms22136764

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Full text: Available Collection: International databases Database: MEDLINE Main subject: Antiviral Agents / Dexamethasone / COVID-19 Drug Treatment / Hypothalamo-Hypophyseal System / Inflammation Type of study: Prognostic study Limits: Humans Language: English Year: 2021 Document Type: Article Affiliation country: Ijms22136764