Dexamethasone for Severe COVID-19: How Does It Work at Cellular and Molecular Levels?

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.

• Authors: Tomoshige Kino, Irina Burd, James H Segars
• Journal: International journal of molecular sciences (Int J Mol Sci) Vol. 22 Issue 13 (Jun 23 2021) ISSN: 1422-0067 [Electronic] Switzerland
• PMID: 34201797 (Publication Type: Journal Article, Review)

Chemical References

• Antiviral Agents
• Dexamethasone

Topics

• Antiviral Agents (pharmacology)
• Dexamethasone (pharmacology)
• Host Microbial Interactions
• Humans
• Hypothalamo-Hypophyseal System (physiology)
• Immunity, Innate
• Inflammation (drug therapy)
• SARS-CoV-2 (drug effects, physiology)
• Severity of Illness Index
• Virus Replication (drug effects)
• COVID-19 Drug Treatment