Adrenal function, morbidity and mortality in patients with COVID-19

Reports of impaired glucocorticoid response in patients with severe COVID-19, associated with increased mortality, have led to the hypothesis that the beneficial effects of dexamethasone in these patients may be mediated by correction of adrenal insufficiency. Considering the limited reliability of total cortisol (TC) in critically ill patients, we sought to assess the incidence of adrenal insufficiency and its relation to negative outcomes according to dexamethasone treatment, using serum free cortisol (SFC). Retrospective analysis of 1,971 COVID-19 patients hospitalized in a major medical center from May 2020 to March 2021. In-hospital and 30-day mortality, and the need for ventilation support, were analyzed in relation to SFC levels. The final cohort comprised 241 patients, 53% of whom had moderate to severe disease. Adrenal insufficiency was diagnosed in 3.5–5.8% in patients with mild and moderate disease, and in 7% of patients with severe disease. SFC was a strong independent variable for all outcome measures, with an Odds Ratio of 1.933 (1.299–2.877), p = 0.001; 2.673 (1.770–4.037), p < 0.001; and 1.515 (1.136-2.0), p = 0.005, for in-hospital mortality, 30-day mortality and the need for assisted ventilation, respectively. Dexamethasone-treated patients exhibited the same pattern of disease-severity-driven cortisol levels, as seen in the whole cohort. Adrenal insufficiency is rare and unrelated to the beneficial effects of dexamethasone in COVID-19 patients. SFC is a strong predictor of adverse outcomes, emerging as a superior biomarker for disease severity and prognosis, compared to other clinical and inflammatory parameters.