Tocilizumab for Treatment of COVID-19 Cytokine Storm- Sohail Zahid

June 06, 2020

There is growing evidence that the rapid progression from mild to severe symptoms in COVID-19 is due to cytokine storm. During this process, the virus rapidly replicates and activates inflammatory cytokines, which leads to vascular leak, acute lung injury, and acute respiratory distress syndrome.

In August 30, 2017, the FDA approved tocilizumab for cytokine storm syndrome. Tocilizumab is a monoclonal antibody against the interleukin-6 (IL-6) receptor, and IL-6 cytokine has been shown to be a key cytokine responsible for fever and acute phase reactions in inflammation.

Treatment of Severe COVID-19 with Tocilizumab

Recently, Xu et al showed that tocilizumab is effective for treating patients with severe COVID-19 infection. Source: http://www.chinaxiv.org/abs/202003.00026

In their study, 21 patients were treated with tocilizumab. These patients had severe infection, which the authors defined as a respiratory rate > 30 breaths per minute, an oxygen saturation < 93%, and a PaO2/FiO2 ratio < 300 mm Hg. Every patient had elevated IL-6 levels (mean of 132 pg/ml, normal is < 7 pg/ml), CT findings of ground glass opacities with focal consolidation in the peripheral lungs, and elevated C-reactive protein levels (mean of 75 mg/L).

However, patients had dramatic improvement with this medication. After a few days with tocilizumab, patients had a significant reduction in inflammatory marker levels, reduction of fever, reduction of their inspired oxygen requirement, and improvement of their oxygen saturation.

Source: Xu et al. 2020
http://www.chinaxiv.org/abs/202003.00026

Patients also had significant reduction of their abnormal imaging findings on CT. In the figure below, we can clearly see that the amount of ground glass opacification in three patient lungs significantly declined.

Source: Xu et al. 2020
http://www.chinaxiv.org/abs/202003.00026

19/21 of the patients eventually were discharged home. 2 are still hospitalized, but now are in stable condition with improvement of symptoms and without fever.

China Approves Tocilizumab

In light of these results, China’s National Health Commission approved tocilizumab for patients with high IL-6 levels and serious lung damage. These treatment guidelines are available here: http://www.nhc.gov.cn/yzygj/s7652m/202003/a31191442e29474b98bfed5579d5af95.shtml

China National Health Commission Report for Treatment of COVID-19

Italian Experience with Tocilizumab

There have also been positive reports (albeit very limited) in Italy with this medication. In Napoli, three patients were reported to improve with this Toliciumab according to the Dr. Paolo Ascierto, the head of clinical immunology. Source: http://www.ansa.it/english/news/general_news/2020/03/13/3-patients-get-better-on-arthritis-drug_90d4764d-d93f-463e-ab07-168b34b084d0.html

Clinical Trials

Genentech is launching several clinical trials with tocilizumab in the United States, taly, and China. Source:https://www.genengnews.com/virology/coronavirus/genentech-launches-phase-iii-trial-of-actemra-as-coronavirus-treatment/. I’m optimistic that this is another medication that can be used in our global fight against COVID-19.

 

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