Intravenous Tocilizumab Therapy can tackle Cytokine Storm in COVID-19 patients

Chitra Roy, University of Calcutta

Since its emergence, COVID-19 has been constantly challenging the medical health system across the globe. COVID-19 infection is primarily accompanied by the aggressive inflammatory response with the release of excessive amounts of pro-inflammatory cytokines which are called ‘Cytokine Storm’. The immune response of the host to SARS-CoV-2 virus is extremely hyperactive leading to an extreme inflammatory reaction. Studies of cytokine profile from COVID-19 patients have shown that the ‘cytokine storm’ is directly related to massive alveolar damage, respiratory failure and multi-organ dysfunction. Patients showing these severe manifestations of the disease have elevated levels of Interleukin-6 (IL-6) which is a pro-inflammatory cytokine contributing to the cytokine storm. So, if IL-6 can be targeted, the disease progression can drastically reduce. 

Tocilizumab is the FDA approved recombinant humanized monoclonal antibody that can specifically target these IL-6 receptors. Tocilizumab therapy in COVID-19 patients in advanced disease cases showing severe symptoms has documented favourable outcomes. Both modes of administration i.e. intravenous (IV) and subcutaneous (SC) formulations have almost equal effects. However, the pharmacokinetic profiles of these two modes of administration differ significantly. Subcutaneous injections have a delayed yet sustained effect while Intravenous injections are more intensive but have a short-lived effect. 

But which of these two modes of tocilizumab administration is better to tackle the cytokine storm? To understand this, a research team in Brooklyn, USA made a comparative analysis of IV and SC tocilizumab therapy in COVID-19 patients to report which mode of administration can have better respiratory and clinical outcomes. 

Their study started with 125 COVID-19 positive patients with respiratory distress (peripheral oxygen saturation < 93% on room air) who were eligible for tocilizumab therapy. Among them, 82 patients had severe disease (receiving supplemental oxygen) and 43 of them were on mechanical ventilation and critically ill. However, the patients received standard treatment with hydroxychloroquine, azithromycin and a short course of corticosteroids. Only the mode of administration of tocilizumab differed. 65 patients received intravenous tocilizumab and 60 patients received subcutaneous tocilizumab. 

The researchers reported that they found divergent yet promising outcomes in COVID-19 patients for IV and SC administration. According to their report, after 3 days of tocilizumab therapy, 52% of patients from the IV group and 32% from SC group showed improved respiratory parameters. After 7 days, improvements differed. 52% of patients from IV and 28% from SC was reported. Their findings show improvements in respiratory parameters and lower in-hospital mortality in the patients who received IV tocilizumab therapy in comparison to those who received SC tocilizumab therapy. They also reported that the dose of corticosteroids was higher in patients who received IV tocilizumab which proved to benefit them by reducing mortality. Through their reports, they concluded that a combination of tocilizumab and corticosteroids has an additive effect in dealing with the cytokine storm in advanced COVID-19 cases and the IV mode of administration of tocilizumab is favoured over SC mode for better clinical results.

Also read: Structural and Functional Inhibition of CHIKV by CHK-124 and CHK-263mAbs

Reference: https://www.sciencedirect.com/science/article/pii/S1201971220321640

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