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

Climente‐Martí, Mónica; Ruiz‐Millo, Oreto; López‐Cruz, Ian; Atienza‐García, Ángel; Martínez‐Moragón, Eva; Garijo‐Gómez, Emilio; López‐Grima, María Luisa; Zaragoza‐Crespo, Rafael; Llau‐Pitarch, Juan Vicente; Bautista‐Rentero, Daniel; Nogueira‐Coito, José Miguel; Ripollés‐González, Tomás; Marco‐Artal, María Antonia; Romero‐Serrano, Ramón; Dolz‐Sinisterra, Francisco; López‐Estudillo, Rosario

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.