Introduction

SARS COV 2 is a member of Corona virus family, which was first recognized in December 2019 in the Chinese city of Wuhan and caused what is known nowadays as the COVID 19 pandemic (Cascella, Rajnik, Cuomo, Dulebohn, & Di Napoli, 2020). The virus is believed to be transmitted by droplets and aerosols causing various clinical conditions ranging from mild flu-like symptoms up to very severe conditions such as acute respiratory distress syndrome (ARDS) (Jayaweera, Perera, Gunawardana, & Manatunge, 2020). Expected death rate among severe ARDS cases is estimated to be up to 62 % (Huang et al., 2020) which is assumed to be a result of what is known as a cytokine storm (Ulhaq & Soraya, 2020). Global attention was therefore paid to the emerging pandemic, in particular the development of new vaccines (Chugh, 2020).
Expanding evidence shows that inflammatory mediators, such as interferons, interleukins, chemokines, tumor-necrotic factors, etc, may be activated by severe COVID-19 condition in the case of a hyperactive immunological response (Yuki, Fujiogi, & Koutsogiannaki, 2020). These mediators are inherent in the innate immune system that attacks foreign infectious agents. However, in very severe conditions it triggers a life-threatening immunological reaction, including a massive release of cytokines which is supposed to cause a cytokine storm (Ye, Wang, & Mao, 2020). This cytokine storm is followed by the immune system attacking the body, which in turn causes ARDS and multiple organ failure (Siracusano, Pastori, & Lopalco, 2020; Z. Xu et al., 2020). Recent studies have demonstrated that patients with severe COVID-19 have elevated serum levels of pro-inflammatory cytokines, including interleukins-6 (IL-6) (Huang et al., 2020; Wang et al., 2007).
Based on that hypothesis, modulating the hyperinflammatory status associated with COVID-19 has been targeted by some drugs in clinical trials including dexamethasone that showed promising improvement in RECOVERY trial (Horby et al., 2020), while the others failed to show significant improvement such as hydroxychloroquine in a recent meta-analysis of clinical trials (Elsawah, Elsokary, Elrazzaz, & ElShafey, 2020).
Tocilizumab is a humanized anti-IL-6 receptor IgG1 monoclonal antibody used for the treatment of rheumatoid arthritis and other chronic inflammatory diseases (Arnaldez et al., 2020). By blocking of IL-6- receptor binding, tocilizumab inhibits signal transduction mediated by IL-6 (Nishimoto & Kishimoto, 2008). Chi Zhang in China first highlighted the cytokine storm hypothesis in severe COVID-19 and the potential impact of tocilizumab against IL-6 and recommended further evidence-based studies to co-relate the potential benefits (Chi, Zhao, Jia-Wen, Hong, & Gui-Qiang, 2020). Furthermore, Xiaoling Xu et al ., claimed effective clinical improvement and successful repression of clinical deterioration in severe COVID-19 patients in their single arm observational study (X. Xu et al., 2020).
Another observational case control study conducted in Italy by Ruggero Capra et al ., showed promising data showing a significant reduction in the mortality rates in the tocilizumab group compared to the control group (Capra et al., 2020). On the other hand, a phase 3 clinical trial conducted by Roche failed to show beneficial outcome regarding clinical status (Hoffmann-La Roche, 2020). Meanwhile, cohort studies were conducted to investigate different outcomes including the overall improvement, length of stay, mortality rates and safety profile (Campochiaro et al., 2020; Colaneri et al., 2020; Guaraldi et al., 2020). In view of the conflicting results, we aimed to systemically review these cohort studies and conduct an updated meta-analysis to provide the best evidence. Our stated objectives are to disclose possible protective effects of tocilizumab from the need for mechanical ventilation and mortality in severe COVID-19 patients, to pool any clinical improvement associated with tocilizumab use, and to summarize the adverse effects reported with tocilizumab use in severe COVID-19 patients.