In the beginning of the coronavirus disease 2019 (COVID-19) pandemic, a disease caused by the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), corticosteroids were contraindicated in the management of these patients. Few months later, the demonstration that, like a sepsis, COVID-19 is mainly driven by a deregulated hyperinflammatory host response to the virus triggered a renewed interest in corticotherapy. Eventually, clinical trials convincingly reported clinical benefits from corticosteroids , which became the standard of care for patients with COVID-19 pneumonia and requirement of oxygen supplementation. The immunomodulatory effects of glucocorticoids are mediated mainly by the glucocorticoid-glucocorticoid receptor pathway, in which the glucocorticoid-induced leucine zipper (GILZ) protein plays a major role. GILZ is strongly induced by glucocorticoids and contributes to the regulation of immune cell activation including the synthesis and release of cytokines and chemokines mainly by inhibiting the nuclear factor kB. GILZ is expressed in almost all immune cells, and its expression by monocytes/macrophages is of the utmost importance to control inflammation.