Division of Infectious Diseases, Department of Internal Medicine, Seoul St. Mary's Hospital, College of Medicine, The Catholic University of Korea, Seoul, Korea.
Vaccine Bio Research Institute, College of Medicine, The Catholic University of Korea, Seoul, Korea.
J Korean Med Sci. 2024 Sep 2;39(34):e255. doi: 10.3346/jkms.2024.39.e255.
Systemic corticosteroids have become the standard of care for severe to critically ill patients with coronavirus disease 2019 (COVID-19). However, the real-world efficacy and safety outcomes associated with a higher dose of corticosteroids remain uncertain.
We conducted a nationwide, population-based, matched cohort study of severe to critically ill adult patients with COVID-19 between January 2020 and June 2021 in Korea using the National Health Information Database. Patients using systemic corticosteroids were included and high-dose corticosteroid use was defined as a daily mean prescribed dose of more than 6 mg of dexamethasone. We then employed a proportional hazard regression model to identify prognostic factors for 28-day all-cause mortality and conducted a Fine and Gray regression model to assess risk factors for developing COVID-19-associated pulmonary aspergillosis (CAPA).
During the study period, 102,304 patients with COVID-19 were screened, 5,754 met the eligibility criteria, and 2,138 were successfully matched. The mean prescribed daily dose was 4.2 mg and 13.4 mg in the standard- and high-dose groups, respectively, and the mean duration of use was not different between the groups. High-dose corticosteroid use independently increased all-cause mortality at 28 days (adjusted hazard ratio [aHR], 1.48; 95% confidence interval [CI], 1.25-1.76) and 90 days (aHR, 1.63; CI, 1.44-1.85) after admission. Subgroup analysis revealed a statistically significant elevation in the risk of mortality among patients using low-flow or high-flow nasal cannulas, with aHRs of 1.41 and 1.46, respectively. No significant impact of high-dose steroids was observed, even in patients who underwent mechanical ventilation at 28 days (aHR, 1.17; CI, 0.79-1.72). As a safety outcome, high-dose corticosteroid use showed an association with the development of CAPA (aHR, 2.97; 95% CI, 0.94-9.43).
Among severe to critically ill patients with COVID-19, high-dose corticosteroid use was associated with increased 28-day all-cause mortality and showed a trend toward the development of CAPA.
全身性皮质类固醇已成为治疗 2019 年冠状病毒病（COVID-19）重症和危重症患者的标准治疗方法。然而，与更高剂量皮质类固醇相关的实际疗效和安全性结果仍不确定。
我们使用国家健康信息数据库，在 2020 年 1 月至 2021 年 6 月期间，对韩国重症和危重症成人 COVID-19 患者进行了一项全国性、基于人群的匹配队列研究。纳入使用全身皮质类固醇的患者，高剂量皮质类固醇的使用定义为每日平均处方剂量超过 6 毫克地塞米松。然后，我们使用比例风险回归模型确定 28 天全因死亡率的预后因素，并使用 Fine 和 Gray 回归模型评估发生 COVID-19 相关肺曲霉病（CAPA）的危险因素。
在研究期间，筛选了 102304 名 COVID-19 患者，符合入选标准的有 5754 名，成功匹配了 2138 名。标准剂量组和高剂量组的平均每日处方剂量分别为 4.2 毫克和 13.4 毫克，两组的平均使用时间无差异。高剂量皮质类固醇的使用独立增加了 28 天（调整后的危险比[aHR]，1.48；95%置信区间[CI]，1.25-1.76）和 90 天（aHR，1.63；CI，1.44-1.85）的全因死亡率。亚组分析显示，在使用低流量或高流量鼻导管的患者中，死亡率风险显著升高，aHR 分别为 1.41 和 1.46。在 28 天接受机械通气的患者中，高剂量类固醇没有显著影响（aHR，1.17；CI，0.79-1.72）。作为一项安全结果，高剂量皮质类固醇的使用与 CAPA 的发生有关（aHR，2.97；95%CI，0.94-9.43）。
在 COVID-19 重症和危重症患者中，高剂量皮质类固醇的使用与 28 天全因死亡率的增加相关，并显示出 CAPA 发展的趋势。
