SAT-446 Cortisol Concentrations in COVID-19 and Influenza: a Comparative Study

Abstract Disclosure: C. Champion: None. M. Lui: None. Z. Wu: None. M.J. McPhaul: None. P. Mudd: None. A. Diwan: None. S. Dhindsa: None. Background: Acute infectious illnesses result in activation of the hypothalamic-pituitary-adrenal (HPA) axis, decreased metabolism of cortisol to inactive cortisone, and decrease in cortisol binding globulin. This leads to an increase in free cortisol, which may have implications for the inflammatory response to the illness. We compared plasma total and free cortisol, cortisone and ACTH in patients with COVID-19, influenza, or other respiratory illnesses. Methods: We utilized blood samples that were prospectively collected in 2019 and 2020 from patients who were confirmed to have COVID-19 infection (COV cohort, 250 patients), influenza (INF cohort, 56 patients) or respiratory illnesses that were not positive for COVID or influenza (OTH cohort, 67 patients). Total Cortisol and cortisone were measured by LC-MS/MS. For plasma free cortisol, the specimen was treated by equilibrium dialysis before introduction to LC-MS/MS analysis. ACTH was measured by immunoassay. Averages are presented as mean ± SD or median [25th, 75th percentile]. Comparisons among groups were made by t-test, ANOVA, or non-parametric tests as appropriate. Results: Mean age was 56±17 years and 46% were female. We divided patients into groups based on the severity of illness: “severe” (those who required ICU care or died), “moderate” (hospitalized but not severe) and “mild” (not admitted). The COV cohort had 94, 134 and 22 patients in severe, moderate and mild groups; the INF cohort had 15, 41 and no patients in severe, moderate and mild groups; the OTH cohort had 8, 19 and 40 patients in severe, moderate and mild groups respectively. The free cortisol concentrations were 1.42 [0.78, 2.37], 0.73 [0.39, 1.32] and 0.33 [0.13, 0.79] µg/dL in severe, moderate and mild groups (p<0.001) in COV cohort. The total cortisol concentrations were 17.6 [12.3, 21.3], 13.7 [9.2, 18.9] and 6.0 [4.1, 11.9] µg/dL in severe, moderate and mild groups (p<0.001) in COV cohort. The free cortisol concentrations in OTH cohort were 2.33 [0.56, 3.69], 0.49 [0.20, 1.00] and 0.36 [0.18, 0.57] µg/dL in severe, moderate and mild groups (p=0.02). Total cortisol showed a similar pattern. In contrast, free cortisol concentrations were similar in severe and moderate groups in INF cohort (0.70 [0.19, 2.08] and 0.46 [0.24, 1.15] µg/dL, p=0.30). Total cortisol concentrations were also similar in those two groups (p=0.62) in INF cohort. Cortisone and ACTH were not different among the groups in any cohort. Severe COV group had higher free cortisol than severe INF group (p=0.05) but not severe OTH group (p=0.59). Conclusion: We found that free cortisol concentrations increase in response to severity of illness in patients with and without COVID-19, except in those with INF. It is not known if the lack of elevation of cortisol in severe INF is adaptive (limiting excessive and harmful inflammation) or maladaptive (limiting the capacity to fight infection with inflammation). Presentation: Saturday, July 12, 2025