Efficacy and Safety Outcomes of High-Dose Corticosteroid Use in Severe to Critically Ill Patients With COVID-19: A Nationwide Population-Based Study (Preprint)

• DOI: 10.2196/preprints.48660
• Publication Date: 2023-05-03T13:18:11Z
• Authors: Raeseok Lee; Dong-Gun Lee; Sung-Yeon Cho; Dukhee Nho

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.

OBJECTIVE We aimed to identify the real-world efficacy and safety outcomes associated with a higher dose of corticosteroids for severe to critically ill patients with COVID-19.

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. Overall mortality and risk of COVID-19-associated pulmonary aspergillosis (CAPA) according to corticosteroid dose were examined.

RESULTS During the study period, 102,304 patients 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 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 who exclusively relied on either a low-flow or high-flow nasal cannula, with aHR of 1.41 (95% CI: 1.10-1.81) and 1.46 (95% CI: 1.09-1.95) 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 a notable association with the development of CAPA (aHR, 2.97; 95% CI, 0.94–9.43).

CONCLUSIONS Among severe to critically ill patients with COVID-19, high-dose corticosteroid use resulted in increased 28-day all-cause mortality and also showed a strong association with the development of CAPA.