4.1 IL-6 inhibitor
Coordinated cytokine response is a necessary condition for host immune response. Nevertheless, uncoordinated response results in excessive inflammation in some patients infected with COVID-19. The concentration of cytokines, granulocyte-macrophage colony stimulating factor and interleukin-6 in plasma are higher than in non-infected people. This not only suggests that cytokine secretion is related to the severity of the disease, but also indicates that inhibition of excessive inflammatory response may be an adjuvant therapy for COVID-19 (Guan, Ni, Hu, Liang, Ou, He, Liu, Shan, Lei, Hui, Du, Li, Zeng, Yuen, Chen, Tang, Wang, Chen, Xiang, Li, Wang, Liang, Peng, Wei, Liu, Hu, Peng, Wang, Liu, Chen, Li, Zheng, Qiu, Luo, Ye, Zhu, Zhong, et al., 2020). A clinical result from Chinese research reveals that IL-6 may probably be a key to this inflammation (F. Zhou et al., 2020). Therefore, it may reverse this process and improve clinical conditions to direct monoclonal antibodies towards IL-6.
Tocilizumab, an interleukin-6 (IL-6) receptor blocking antibody, serves as an inhibitor to IL-6-mediated signal transduction hence control inflammation (Le et al., 2018). An early clinical report revealed that 91% of 21 patients with COVID-19 showed improvement in respiratory function and decline in fever after taking tocilizumab. Preliminary data showed that tocilizumab reduced mortality. It provides immediate improvement severe cases of COVID-19. Tocilizumab treatment resolved symptoms, such as hypoxemia and CT shadow changes (X. Xu et al., 2020). Mechanistically, tocilizumab regulates IL-6 thereby promote the release of inflammatory cytokines. It is therefore an effective drug for treating patients with severe COVID-19 (Zhang, Wu, Li, Zhao, & Wang, 2020).
Currently, multiple randomized controlled trials for single or combined use of tocilizumab in patients with COVID-19 complicated with severe pneumonia are ongoing in keeping with the Chinese national treatment guidelines (Sanders et al., 2020). For example, Some administrations also study Tocilizumab with favipinavir, in order to realize the potential synergistic effect of the two drugs (NCT04310228). Furthermore, it should also be noted the potential adverse drug reactions. Tocilizumab can increase the risk of infections, especially infections of the upper airways. It can also pose risk of AST transaminases, hypertension, hematological effects, hepatotoxicity, gastrointestinal perforation, hypersensitivity reactions to the active principle (Sheppard, Laskou, Stapleton, Hadavi, & Dasgupta, 2017).