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.