J Korean Med Sci.  2024 Sep;39(34):e255. 10.3346/jkms.2024.39.e255.

High-Dose Corticosteroid Use in Severe to Critically Ill Patients With COVID-19: A Nationwide PopulationBased Matched Cohort Study

• Lee R
• Cho SY
• Lee DG
• Nho D

• KMID: 2559201
• DOI: http://doi.org/10.3346/jkms.2024.39.e255

Abstract

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.

Keyword

COVID-19; Glucocorticoids; Survival; COVID-19-Associated Pulmonary Aspergillosis

Figure

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  Fig. 1 Schematic flow of patient selection from the National Health Information database.CAM = COVID-19-associated mucormycosis, COVID-19 = coronavirus disease 2019, NHID = National Health Information Database.

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  Fig. 2 All-cause mortality at 28 days from the matched cohort, analyzed using the Kaplan-Meier method.CI = confidence interval, HR = hazard ratio.

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  Fig. 3 Impact of high-dose corticosteroid on 28-day overall mortality in subgroups stratified by age, sex, comorbidities, and levels of respiratory support. The hazard ratio represents the risk of mortality associated with high-dose corticosteroid use in each subgroup.HR = hazard ratio, CI = confidence interval, HFNC = high-flow nasal cannula, MV = mechanical ventilation.

• 

  Fig. 4 Cumulative incidence of COVID-19-associated pulmonary aspergillosis from the matched cohort, analyzed using the Kaplan-Meier method.CAPA = COVID-19-associated pulmonary aspergillosis, HR = hazard ratio, CI = confidence interval.

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