Elevated Serum Free Cortisol is a Strong Predictor of Mortality in Hospitalized Patients with Covid-19 Irrespective of Dexamethasone Treatment

Serum total cortisol has been linked to increased mortality in patients with Covid-19, but its reliability in critically ill patients is limited. We examined the association between serum free cortisol levels (SFC) and clinical outcomes in patients hospitalized with Covid-19 between 5/5/2020-1/3/2021.

Methods:
SFC was measured in blood samples collected at patient’s admission, prior to medical treatment. Patients’ files were reviewed retrospectively.

Results:
There were 241 patients (78% female), mean (SD) age 67.4 (18.5), of whom 47.3% received dexamethasone treatment (DT). The in-hospital mortality, 30-day mortality and the need for assisted ventilation (AV) were 8.7%, 14.9% and 18.3% respectively. SFC levels were higher in patients who died in hospital [3.74 (2.8) vs. 1.4 (0.85) µg/dl, p<0.0001], or within 30 days [3.01 (2.3) vs 1.32 (0.77) µg/dl, p<0.0001] or who required assisted ventilation [2.77 (2.4) vs. 1.4 (0.8) µg/dl, p<0.0001]. SFC levels were significantly higher in patients with diabetes, hypertension, cardiovascular disease and chronic renal failure. The area under the ROC curve (AUC) to discriminate 30-day and in-hospital mortality was higher for SFC compared with IL-6, CRP, ferritin and LDH. SFC levels were higher in dexamethasone treated compared with untreated patients. Within treated patients, SFC levels were higher in those who died in hospital (3.58 (2.8) vs 1.56 (0.9) µg/dl, p <0.0001] or within 30 days [3.1(2.6) vs 1.56 (0.9) µg/dl, p<0.0001], compared with those that survived.

Conclusions:
SFC levels strongly predict in-hospital and 30-day mortality as well as the need for AV in hospitalized patients with Covid-19, irrespective of DT.