#VisualAbstract: High-dose corticosteroids increase morbidity and mortality among hypoxic COVID-19 patients

1. Patients in the high-dose dexamethasone group reported significantly greater mortality within 28 days of treatment.

2. Occurrence of non-COVID-19 pneumonia and hyperglycemia was more frequent in the high-dose dexamethasone group compared to usual care.

Evidence Rating Level: 1 (Excellent)

Study Rundown: Low-dose corticosteroids has been shown to have clinical benefit among patients with COVID-19 who are hypoxic but not requiring ventilatory support. However, the optimal dose of corticosteroids in this cohort remains unclear and there is limited evidence on whether higher doses of steroids confer morbidity or mortality benefits. This randomized controlled trial aimed to compare the safety and efficacy of high-dose corticosteroids in patients hospitalized with COVID-19 requiring supplemental oxygen but not invasive mechanical ventilation. The primary outcome was 28-day mortality while key secondary outcomes were time to discharge from hospital and invasive mechanical ventilation. According to study results, patients assigned to the high-dose corticosteroid group reported higher mortality and greater adverse outcomes compared to usual care. This study was strengthened by a randomized design with individuals from multiple centers in multiple countries, thus increasing its generalizability.

Click to read the study in The Lancet

In-depth [randomized-controlled trial]: Between May 25, 2021, and May 13, 2022, 2339 patients were screened for eligibility across 93 sites in 6 countries. Included were patients ≥ 18 years with clinically suspected or laboratory-confirmed COVID-19 and hypoxia (SpO2 < 92% on room air). Altogether, 1272 patients (659 in high-dose steroids and 613 in usual care) were included in the intention-to-treat analysis. The high-dose corticosteroid group received dexamethasone 20 mg daily for five days followed by dexamethasone 10 mg daily while the usual care group received dexamethasone 6 mg daily for 10 days or until hospital discharge. The majority of patients (60%) were male and 19% had diabetes at baseline. The primary outcome of 28-day mortality was significantly greater in the high-dose steroid group compared to usual care (19% vs. 12%, rate ratio [RR] 1.59, 95% confidence interval [CI] 1.20-2.10, p=0.0012). Patients in the high-dose steroid group also reported an increased incidence of non-COVID-19 pneumonia (10% vs. 6%, 95% CI 0.7-6.6) and hyperglycemia (22% vs. 14%; absolute difference = 7.4%, 95% CI 3.2-11.5) compared to the low-dose steroid group. Overall, findings from this study suggest that among COVID-19 patients with hypoxia not requiring invasive mechanical ventilation, high-dose steroids significantly worsened clinical outcomes.

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