Fig. 3.

Corticosteroids may facilitate SARS-CoV-2 entry by affecting blood glucose levels and kidney function. Corticosteroids can be categorized into the mineralocorticoids and the glucocorticoids. The mineralocorticoids, which mimic the actions of aldosterone, affect kidney function by increasing the Na⁺ and H₂O reabsorption. Because this mechanism does not promote Ang II formation, it is not expected to contribute majorly to increased ACE2 expression. On the other hand, corticosteroids affect the liver by increasing its capacity for gluconeogenesis. Muscles enhance protein breakdown into amino acids, which are carried to the liver for conversion into glucose. Further, glucocorticoids promote the actions of glycogen, and inhibit the actions of insulin. This gluconeogenic action coupled with insulin resistance leads to hyperglycemia in susceptible persons, which result in osmotic diuresis that can substantially reduce plasma volume. The body compensates by upregulating ACE to increase Ang II levels, thereby increasing Na⁺ and H₂O reabsorption and vasoconstricting blood vessels. An expected increase in ACE2 to counteract increased Ang II action is proposed to be the mechanism of how corticosteroids, precisely glucocorticoids, can facilitate ACE2-mediated SARS-CoV-2 entry to cells and viral replication in COVID-19.