Clausen Clara Lundetoft, Johannsen Trine Holm, Skakkebæk Niels Erik, Frederiksen Hanne, Juul Anders, Benfield Thomas
Center of Research & Disruption of Infectious Diseases, Department of Infectious Diseases, Copenhagen University Hospital - Amager and Hvidovre, Hvidovre, Denmark.
Department of Growth and Reproduction, Copenhagen University Hospital - Rigshospitalet, Copenhagen, Denmark.
Endocr Connect. 2024 Jul 13;13(8). doi: 10.1530/EC-24-0093. Print 2024 Aug 1.
In the context of severe coronavirus disease 2019 (COVID-19) illness, we examined endogenous glucocorticoid concentrations, steroidogenic enzyme activity, and their correlation with inflammation and patient outcomes. This observational study included 125 hospitalized COVID-19 patients and 101 healthy individuals as a reference group. We utilized LC-MS to assess serum concentrations of 11-deoxycortisol, cortisol, and cortisone, as well as activities of steroidogenic enzymes (11β-hydroxylase and 11β-hydroxysteroid-dehydrogenase type 1). Cox proportional hazards regression analysis and competing risk analysis were employed to analyze associations between glucocorticoid concentrations and outcomes, adjusting for relevant factors. In patients with COVID-19, cortisol concentrations were higher and cortisone concentrations were lower compared to the reference group, while 11-deoxycortisol concentrations were similar. Steroidogenic enzyme activity favored cortisol production. Correlations between glucocorticoid concentrations and inflammatory markers were low. A doubling in concentrations cortisol, was associated with increased 90-day mortality and mechanical ventilation (HR: 2.40 95% CI: (1.03-5.59) , P = 0.042 and HR: 3.83 (1.19-12.31), P = 0.024). A doubling in concentrations of 11-deoxycortisol was also associated to mortality (HR: 1.32 (1.05-1.67), P = 0.018), whereas concentrations of cortisone were associated with mechanical ventilation (HR: 5.09 (1.49-17.40), P = 0.009). In conclusion, serum concentrations of glucocorticoid metabolites were altered in patients hospitalized with severe COVID-19, and steroidogenic enzyme activity resulting in the conversion of cortisone to biologically active cortisol was preserved, thus not favoring critical-illness-related corticosteroid insufficiency at the enzymatic level. Glucocorticoid release did not counterbalance the hyperinflammatory state in patients with severe COVID-19. High serum concentrations of 11-deoxycortisol and cortisol were associated with 90-day mortality, and high serum concentrations of cortisol and cortisone were associated with mechanical ventilation.
在2019年冠状病毒病（COVID-19）重症患者中，我们检测了内源性糖皮质激素浓度、类固醇生成酶活性，以及它们与炎症和患者预后的相关性。这项观察性研究纳入了125例住院COVID-19患者和101名健康个体作为参照组。我们利用液相色谱-质谱联用技术（LC-MS）评估11-脱氧皮质醇、皮质醇和可的松的血清浓度，以及类固醇生成酶（11β-羟化酶和11β-羟类固醇脱氢酶1型）的活性。采用Cox比例风险回归分析和竞争风险分析来分析糖皮质激素浓度与预后之间的关联，并对相关因素进行校正。与参照组相比，COVID-19患者的皮质醇浓度较高，可的松浓度较低，而11-脱氧皮质醇浓度相似。类固醇生成酶活性有利于皮质醇的生成。糖皮质激素浓度与炎症标志物之间的相关性较低。皮质醇浓度翻倍与90天死亡率增加和机械通气相关（风险比：2.40，95%置信区间：(1.03 - 5.59)，P = 0.042；风险比：3.83(1.19 - 12.31)，P = 0.024）。11-脱氧皮质醇浓度翻倍也与死亡率相关（风险比：1.32(1.05 - 1.67)，P = 0.018），而可的松浓度与机械通气相关（风险比：5.09(1.49 - 17.40)，P = 0.009）。总之，重症COVID-19住院患者的糖皮质激素代谢产物血清浓度发生了改变，导致可的松转化为生物活性皮质醇的类固醇生成酶活性得以保留，因此在酶水平上不支持与危重症相关的皮质类固醇功能不全。糖皮质激素释放未能抵消重症COVID-19患者的高炎症状态。高血清浓度的11-脱氧皮质醇和皮质醇与90天死亡率相关，高血清浓度的皮质醇和可的松与机械通气相关。
