Use of glucocorticoids in patients with adrenal insufficiency and COVID-19 infection

In March 2020, severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), the cause of coronavirus disease (COVID-19), reached pandemic level with a high global mortality rate. The initial immune response to viral load is followed by an uncontrolled cytokine storm with hyperinflammation and immunosuppression. In the patients who are critically ill, infected alveolar epithelial cells trigger the release of inflammatory cytokines, which activates fibroblasts. Subsequently, uncontrolled viral propagation induces cytotoxicity and hyperactivation of immune cells. The cytokine storm leads to increased clotting, vascular inflammation, thromboembolism, and hypotensive shock. Glucocorticoids have both stimulating and inhibitory effects on the immune response. In the initial phases of an infection, physiological glucocorticoid concentrations help to prime the immune system. In turn, this response activates the hypothalamic–pituitary–adrenal (HPA) axis to mild immunosuppression to reduce autoimmunity and cytokine toxicity. In critical illness (eg, COVID-19 pneumonia), HPA activation might be blunted, leading to corticosteroid insufficiency related to critical illness. Patients with adrenal insufficiency have an increased risk of infection due to their depleted innate immunity, characterised by increased monocytes and decreased cytotoxic natural killer cells,which could facilitate the worsening of a SARS-CoV-2 infection into severe acute respiratory distress syndrome. Given the role of the HPA axis in stress priming the immune response, patients with adrenal insufficiency are intuitively at high risk of infection, especially as corticosteroid therapy during infection is still largely tailored empirically, often disregarding timing and dosage. The rationale of the more the better avoids risking inadequate concentrations of corticosteroids. In summary, tailoring of glucocorticoid stress regimens in COVID-19 requires a more evidence-based approach. The pathophysiology of immune response and the systemic complications associated with a SARS-CoV-2 infection set the pace, and the protocol should be adapted to the patient's clinical stage