Why tocilizumab could be an effective treatment for severe COVID-19?

Binqing Fu, Xiaoling Xu, Haiming Wei, Binqing Fu, Xiaoling Xu, Haiming Wei

Abstract

A severe pneumonia-associated respiratory syndrome caused by a new coronavirus was identified in December 2019 (COVID-19), spread rapidly and has become a world-wide public health challenge. About 25% of COVID-19 patients experienced severe complications including acute respiratory distress syndrome (ARDS), and even progressed into an intensive care unit (ICU) admission and died. The exploration for the mortality causes and advancing novel therapeutic development of severe COVID-19 is crucial at the moment. The biopsy samples analysis at autopsy suggested that increased alveolar exudate caused by aberrant host immune response and inflammatory cytokine storm probably impedes alveolar gas exchange and contributes to the high mortality of severe COVID-19 patients. Our research has identified that pathogenic T cells and inflammatory monocytes incite inflammatory storm with large amount of interleukin 6, therefore monoclonal antibody that targets the IL-6 pathways may potentially curb inflammatory storm. Moreover, Tocilizumab treatment that blocking IL-6 receptors showed inspiring clinical results including temperature returned to normal quickly and respiratory function improved. Therefore, we suggest that Tocilizumab is an effective treatment in severe patients of COVID-19 to calm the inflammatory storm and reduce mortality.

Keywords: Acute respiratory distress syndrome (ARDS); COVID-19; IL-6; Inflammatory storm; SARS-CoV-2; Tocilizumab.

Conflict of interest statement

The authors declare no competing interests.

Figures

Fig. 1
Fig. 1
Pathogenic T cells and inflammatory monocytes with high IL-6 secretion may enter the pulmonary circulation in large numbers,incite the inflammatory storm and lead an immune disorder in severe COVID-19 patients
Fig. 2
Fig. 2
Tocilizumab calms the inflammatory storm through blocking IL-6 receptors

References

    1. Channappanavar R, Perlman S. Pathogenic human coronavirus infections: causes and consequences of cytokine storm and immunopathology. Semin Immunopathol. 2017;39:529–539. doi: 10.1007/s00281-017-0629-x.
    1. Wang C, Horby PW, Hayden FG, Gao GF. A novel coronavirus outbreak of global health concern. Lancet. 2020;395(10223):470–473. doi: 10.1016/S0140-6736(20)30185-9.
    1. .
    1. Huang C, Wang Y, Li X, Ren L, Zhao J, Hu Y, Zhang L, Fan G, Xu J, Gu X, et al. Clinical features of patients infected with 2019 novel coronavirus in Wuhan, China. Lancet. 2020;395(10223):497–506. doi: 10.1016/S0140-6736(20)30183-5.
    1. Wang D, Hu B, Hu C, Zhu F, Liu X, Zhang J, Wang B, Xiang H, Cheng Z, Xiong Y, et al. Clinical characteristics of 138 hospitalized patients With 2019 novel coronavirus-infected pneumonia in Wuhan, China. JAMA. 2020 doi: 10.1001/jama.2020.1585.
    1. Tian S, Hu W, Niu L, Liu H, Xu H, Xiao SY. Pulmonary pathology of early phase 2019 novel coronavirus (COVID-19) pneumonia in two patients with lung cancer. J Thorac Oncol. 2020 doi: 10.1016/j.jtho.2020.02.010.
    1. Xu Z, Shi L, Wang Y, Zhang J, Huang L, Zhang C, Liu S, Zhao P, Liu H, Zhu L, et al. Pathological findings of COVID-19 associated with acute respiratory distress syndrome. Lancet Respir Med. 2020;8(4):420–422. doi: 10.1016/S2213-2600(20)30076-X.
    1. Luo W, Yu H, Gou J, Li X, Sun Y, Li J, Liu L. Clinical pathology of critical patient with novel coronavirus pneumonia (COVID-19). Preprints 2020, 2020020407
    1. Croxford AL, Lanzinger M, Hartmann FJ, Schreiner B, Mair F, Pelczar P, Clausen BE, Jung S, Greter M, Becher B. The cytokine GM-CSF drives the inflammatory signature of CCR2 + monocytes and licenses autoimmunity. Immunity. 2015;43:502–514. doi: 10.1016/j.immuni.2015.08.010.
    1. Zhou YG, Fu BQ, Zheng XH, Wang DS, Zhao CC, Qi YJ, Sun R, Tian ZG, Xu XL, Wei HM. Pathogenic T cells and inflammatory monocytes incite inflammatory storm in severe COVID-19 patients. Nat Sci Rev. 2020 doi: 10.1093/nsr/nwaa041.
    1. Xu XL, Han MF, Li TT, Sun W, Wang DS, Fu BQ, Zhou YG, Zheng XH, Yang Y, Li XY, Zhang XH, Pan AJ, Wei HM. Effective treatment of severe COVID-19 patients with tocilizumab. ChinaXiv. 2020;202003(00026):V1.

Source: PubMed

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