Ruiz-Millo O, Pitarch Jvl, López-Estudillo R, Coito Jmn, González Tr, Gómez Eg, Climente-Martí M, Crespo Rz, Sinisterra Fd, Atienza-García Á, Martínez-Moragón E, Rentero Db, Cruz Il, Serrano Rr, López-Grima Ml, and Artal Mam
Background: This study aimed to evaluate the effectiveness and safety of intermediate to high doses of methylprednisolone in patients with COVID-19 pneumonia-induced severe systemic inflammation (PI-SSI). Methods: Between March, 9 and May, 5, 2020 (final follow-up July, 2, 2020), a retrospective cohort study was conducted in hospitalized patients with COVID-19 PI-SSI (≥2 inflammatory biomarkers (IB): temperature ≥38oC, lymphocyte ≤800cell/microL, C-reactive protein ≥100mg/L, lactate dehydrogenase ≥300units/L, ferritin ≥1000mcg/L, D-dimer ≥500ng/mL). Patients received 0.5-1.0mg/kg 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 ICU (day-28) and adverse effects. Kaplan-Meier method and Cox-proportional hazard regression was implemented to analyze the time to event outcomes. Findings: 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 in the corticosteroid group in subgroups 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]. There was no significant difference in patients with ≥2 points improvement on 7-point WHO scale or transferred to ICU. Similar proportion of adverse events was also observed. Interpretation: Intermediate to high-doses of methylprednisolone, initiated between 5-12 days after symptoms onset was associated with a significant reduction in 28-day all-cause mortality in patients with COVID-19 pneumonia and ³3 o ³4 altered IB, independently of the need of respiratory support. Funding: None. Declaration of Interests: MCM reports personal fees from AstraZeneca, Sanofi-Aventis S.A., GlaxoSmithKline, Pierre Fabre Iberica S.A., Grifols S.A., and Baxter S.L., outside the submitted work. AAG reports personal fees from Janssen-Cilag S.A., Merck Sharp Dohme de Espana, and Gilead Sciences, outside the submitted work. EMM reports personal fees from AstraZeneca, Boehringer-Ingelheim, Chiesi, GlaxoSmithKline, Sanofi-Aventis S.A., Novartis, TEVA, and ALK-Abello, outside the submitted work; and declares as a consultant for AstraZeneca, Boehringer- Ingelheim, and GlaxoSmithKline. EGG reports personal fees from ProStrakan Farmaceutica, S.L., outside the submitted work. All other authors declare no competing interests. Ethics Approval Statement: The study was conducted in accordance with the ethical principles of the Helsinki Declaration and was approved by the local Clinical Research Ethics Committee (code 64/20) and classified by the Spanish Agency of Medicines and Medical Devices (HDP-GLU- 2020-05).