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High-Dose Corticosteroid Use in Severe to Critically Ill Patients With COVID-19: A Nationwide Population-Based
Raeseok Lee1,2, Sung-Yeon Cho1,2, Dong-Gun Lee1,3
1Division of Infectious Diseases, Department of Internal Medicine, Seoul St. Mary's Hospital, College of Medicine, The Catholic University of Korea, Seoul, Korea.
Insights
High-dose corticosteroids for severe COVID-19 increase mortality risk and the chance of developing pulmonary aspergillosis. Standard-dose steroids are recommended for better outcomes in critically ill patients.
Area of Science:
- Critical care medicine
- Infectious diseases
- Pharmacology
Background:
- Systemic corticosteroids are standard for severe COVID-19.
- Real-world data on high-dose corticosteroid efficacy and safety in COVID-19 is limited.
Purpose of the Study:
- To evaluate the real-world efficacy and safety of high-dose corticosteroids in severe to critically ill COVID-19 patients.
- To assess the impact of high-dose steroids on mortality and COVID-19-associated pulmonary aspergillosis (CAPA).
Main Methods:
- Nationwide, population-based, matched cohort study in Korea (January 2020 - June 2021).
- Included severe to critically ill COVID-19 patients using systemic corticosteroids.
- High-dose defined as >6 mg/day dexamethasone; analyzed mortality and CAPA using regression models.
Main Results:
- High-dose corticosteroid use was independently associated with increased 28-day (aHR, 1.48) and 90-day (aHR, 1.63) all-cause mortality.
- Increased mortality risk observed in subgroups using nasal cannulas but not mechanical ventilation.
- High-dose steroids showed an association with CAPA development (aHR, 2.97).
Conclusions:
- High-dose corticosteroid use in severe COVID-19 is linked to higher mortality.
- A trend towards increased CAPA development was noted with high-dose steroid use.
Background:
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.
Methods:
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).
Results:
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).
Conclusion:
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.
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