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.
【저자키워드】 Inflammation, Glucocorticoids, Innate immunity, Severe Acute Respiratory Syndrome Coronavirus-2 (SARS-CoV-2), glucocorticoid receptor (GR), type I interferons (IFNs), 【초록키워드】 COVID-19, Dexamethasone, Treatment, coronavirus disease, viruses, SARS-CoV-2, Glucocorticoids, Coronavirus disease 2019, Infectious diseases, Diseases, Respiratory failure, severe COVID-19, Pneumonia, Influenza, SARS-COV-2 infection, Infection, Sepsis, Local, virus, glucocorticoid, activity, Replication, Protein, Viral, viral replication, systemic inflammation, respiratory, characteristic, Viral diseases, mechanism, Bacterial sepsis, Coronavirus-2, Hypothesis, steroid, host cell, infected cells, influenza pneumonia, life-threatening, severe respiratory syndrome, respiratory syndrome coronavirus, encoding proteins, effective, non-infected, develop, caused, significantly, reported, pathologic, facilitate, unique, interfere, not affect, cause, impacted, hypothetical, accompanied, modulated, anti-inflammatory property, glucocorticoid dexamethasone, modulating, potential molecular, 【제목키워드】 Dexamethasone, work,