Steroids and Tocilizumab in Cytokine Storm Syndrome Save

A recent study from the Netherlands has shown that patients with severe COVID-19-associated cytokine storm syndrome (CSS)  with high dose steroids and tocilizumab had a faster recovery, less need for invasive mechanical ventilation and fewer deaths when compared to CSS patients receiving supportive care only.

They studed COVID-19 patients with CSS, defined as rapid respiratory deterioration plus at least two of the following biomarkers: a) C-reactive protein >100mg/L; b) ferritin >900 µg/L; or c) D-dimer >1500 µg/L.

They retrospectively identified those treated with usual care and those with high-dose intravenous methylprednisolone for 5 consecutive days, with our without the interleukin-6 receptor inhibitor, tocilizumab, (8mg/kg body weight, single infusion). Control patients with COVID-19-associated CSS were retrospectively identified from the same time frame and were sex and age match. 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.

A total of 172 patients were studied, all with symptoms of CSS and impending respiratory failure. They compared COVID-19 outcomes in in the treatment group (n=86) to the historic control group (n=86);

Those treated with with methylprednisolone +/- Tocilizumab (43 patients had better outcomes with :

• 79% more achieving the primary outcome (HR: 1.8; 95%CI 1.2 to 2.7)  with faster recovery (7 days earlier)
• 65% less mortality (HR: 0.35; 95%CI 0.19 to 0.65)
• 71% less invasive mechanical ventilation (HR: 0.29; 95%CI 0.14 to 0.65). 

Adverse events were comparable with similar numbers of bacterial infections (8 in the treatment group vs 7 in the control group), although there was a trend towards more pulmonary embolism in the treatment group (p=0.0590). 

The authors believe that their success was related to the timely administration of high dose methylprednisolone, followed by tocilizumab, lead to optimal outcomes in patients with severe COVID-19 infection and impending or active cytokine storm syndrome.