Treatment Combo Successfully Resolves Cytokine Storm in COVID-19

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Researchers writing in the Annals of the Rheumatic Diseases report that a high dose of methylprednisoline with tocilizumab when warranted, may accelerate recovery for COVID-19 patients affected by the cytokine storm syndrome.

The study, which was led by Dr. Sofia Ramiro, a rheumatologist with Zuyderland Medical Center in The Netherlands, was published July 20 in the journal.

Cytokine storm system (CSS) is a potentially life-threatening condition group of conditions that can lead to systemic inflammation, organ damage and potentially death. It is associated with some rheumatic conditions, such as systemic juvenile idiopathic (JIA) and adult-onset Still's disease and now, severe cases of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) in 25 percent of patients often leading to death.

The study, which was conducted in April, included COVID-19 172 patients with associated cytokine storm system and acute respiratory failure. The patients had at least two of the following three biomarkers: Elevated C-reactive protein greater than 100 mg/L; ferritin greather than 900 µg/L; or, D-dimer greater than 1500 µg/L. These patients received a high-dose of intravenous methylprednisolone for five consecutive days (250 mg on day one followed by 80 mg on days two through five). Patients who did not respond to treatment with high doses of methylprednisolone monotherapy after two days, received tocilizumab as add-on treatment.

The treatment group included 86 patients of which 79 percent reached the primary outcome of achieving at least two stages of improvement on a seven-item WHO-endorsed scale for trials in patients with severe influenza pneumonia, or discharge from the hospital. Mortality was down by 65 percent in this group and fewer patients required mechanical ventilation (71 percent less than the control group). None of the 86 patients in the control group received glucocorticoids or tocilizumab.

The authors wrote that cytokine storm system is a treatable complication of COVID-19 and at this point, high-dose glucocorticoids and immunosuppressive treatment may be the best option for patients.

"A strategy involving a course of highdose 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," the authors wrote. "This historically controlled comparison of a strategy with intensive immunosuppression and close monitoring versus a strategy with supportive care only in patients with COVID-19-associated CSS suggests that clinically relevant improvement of respiratory status is 79% more likely, and can be accelerated by a median of 7 days, that hospital mortality can be reduced by 65% and that the need for mechanical ventilation during admission can be reduced by 71%. These outcomes were robust and, especially if confirmed in randomized trials later on, highly relevant from a medical and societal perspective."

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CITATION

Ramiro S, Mostard RLM, Magro-Checa C, et al. Historically controlled comparison of glucocorticoids with or without tocilizumab versus supportive care only in patients with COVID-19-associated cytokine storm syndrome: results of the CHIC study. Annals of the Rheumatic Diseases Published Online First: 20 July 2020. doi: 10.1136/annrheumdis-2020-218479