• Sofia Ramiro, Mostard Rémy L M RLM Department of Pulmonology, Zuyderland Medical Center, Heerlen, Limburg, The Netherlands., César Magro-Checa, Christel M P van Dongen, Tom Dormans, Jacqueline Buijs, Michiel Gronenschild, Martijn D de Kruif, van Haren Eric H J EHJ Department of Pulmonology, Zuyderland Medical Center, Heerlen, Limburg, The Netherlands., Tom van Kraaij, Leers Mathie P G MPG Department of Clinical Chemistry and Hematology, Zuyderland Medical Center, Heerlen, Limburg, The Netherlands., Ralph Peeters, Dennis R Wong, and Landewé Robert B M RBM 0000-0002-0577-6620 Rheumatology, Zuyderland Medical Center, Heerlen, Limburg, The Netherlands. .
• Rheumatology, Zuyderland Medical Center, Heerlen, Limburg, The Netherlands sofiaramiro@gmail.com.
• Ann. Rheum. Dis. 2020 Sep 1; 79 (9): 1143-1151.

ObjectivesTo prospectively investigate in patients with severe COVID-19-associated cytokine storm syndrome (CSS) whether an intensive course of glucocorticoids with or without tocilizumab accelerates clinical improvement, reduces mortality and prevents invasive mechanical ventilation, in comparison with a historic control group of patients who received supportive care only.MethodsFrom 1 April 2020, patients with COVID-19-associated CSS, defined as rapid respiratory deterioration plus at least two out of three biomarkers with important elevations (C-reactive protein >100 mg/L; ferritin >900 µg/L; D-dimer >1500 µg/L), received high-dose intravenous methylprednisolone for 5 consecutive days (250 mg on day 1 followed by 80 mg on days 2-5). If the respiratory condition had not improved sufficiently (in 43%), the interleukin-6 receptor blocker tocilizumab (8 mg/kg body weight, single infusion) was added on or after day 2. Control patients with COVID-19-associated CSS (same definition) were retrospectively sampled from the pool of patients (n=350) admitted between 7 March and 31 March, and matched one to one to treated patients on sex and age. The primary outcome was ≥2 stages of improvement on a 7-item WHO-endorsed scale for trials in patients with severe influenza pneumonia, or discharge from the hospital. Secondary outcomes were hospital mortality and mechanical ventilation.ResultsAt baseline all patients with COVID-19 in the treatment group (n=86) and control group (n=86) had symptoms of CSS and faced acute respiratory failure. Treated patients had 79% higher likelihood on reaching the primary outcome (HR: 1.8; 95% CI 1.2 to 2.7) (7 days earlier), 65% less mortality (HR: 0.35; 95% CI 0.19 to 0.65) and 71% less invasive mechanical ventilation (HR: 0.29; 95% CI 0.14 to 0.65). Treatment effects remained constant in confounding and sensitivity analyses.ConclusionsA strategy involving a course of high-dose methylprednisolone, followed by tocilizumab if needed, may accelerate respiratory recovery, lower hospital mortality and reduce the likelihood of invasive mechanical ventilation in COVID-19-associated CSS.© Author(s) (or their employer(s)) 2020. No commercial re-use. See rights and permissions. Published by BMJ.

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