Impact of intermediate to high doses of methylprednisolone on mortality rate in patients with COVID-19 pneumonia-induced severe systemic inflammation.

ABSTRACT

INTRODUCTION: In addition to respiratory support needs, patients' characteristics to guide indication or timing of corticosteroid treatment in COVID-19 patients are not completely established. This study aimed to evaluate the impact of methylprednisolone on mortality rate in patients with COVID-19 pneumonia-induced severe systemic inflammation (PI-SSI). METHODS: Between 9 March and 5 May 2020 (final follow-up on 2 July 2020), a retrospective cohort study was conducted in hospitalised patients with COVID-19 PI-SSI (≥2 inflammatory biomarkers [IBs] temperature ≥38℃, lymphocyte ≤800 cell/µL, C-reactive protein ≥100 mg/L, lactate dehydrogenase ≥300 units/L, ferritin ≥1000 mcg/L, D-dimer ≥500 ng/mL). Patients received 0.5-1.0 mg/kg of methylprednisolone for 5-10 days or standard of care. The primary outcome was 28-day all-cause mortality. Secondary outcomes included ≥2 points improvement on a 7-item WHO-scale (Day 14), transfer to intensive care unit (ICU) (Day 28) and adverse effects. Kaplan-Meier method and Cox proportional hazard regression were implemented to analyse the time to event outcomes. RESULTS: A total of 142 patients (corticosteroid group n = 72, control group n = 70) were included. A significant reduction in 28-day all-cause mortality was shown with methylprednisolone in patients with respiratory support (HR 0.15; 95% CI 0.03-0.71), with ≥3 (HR 0.17; 95% CI 0.05-0.61) or ≥4 altered IB (HR 0.15; 95% CI 0.04-0.54) and in patients with both respiratory support and ≥3 (HR 0.11; 95% CI 0.02-0.53] or ≥4 altered IB (HR 0.14; 95% CI 0.04-0.51). No significant differences were found in secondary outcomes. CONCLUSION: Intermediate to high doses of methylprednisolone, initiated between 5 and 12 days after symptom onset, was associated with a significant reduction in 28-day all-cause mortality in patients with COVID-19 pneumonia and ≥3 o ≥ 4 altered IB, independently of the need of respiratory support.