期刊论文详细信息
International Journal of Molecular Sciences
Dexamethasone for Severe COVID-19: How Does It Work at Cellular and Molecular Levels?
James H. Segars1  Irina Burd1  Tomoshige Kino2 
[1] Department of Gynecology and Obstetrics, Johns Hopkins University School of Medicine, Baltimore, MD 21205, USA;Laboratory of Molecular and Genomic Endocrinology, Sidra Medicine, Doha 26999, Qatar;
关键词: glucocorticoids;    glucocorticoid receptor (GR);    inflammation;    innate immunity;    severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2);    type I interferons (IFNs);   
DOI  :  10.3390/ijms22136764
来源: DOAJ
【 摘 要 】

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.

【 授权许可】

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