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Unravelling the potentialities of tocilizumab for the development of a potential immunotherapeutic regimen against COVID-19—A narrative review

Manish Dhawan, Kuldeep Dhama, Manisha Parmar, Alisha Sharma, Steffy Angural.




Abstract
Cited by 7 Articles

The severity of COVID-19 (coronavirus disease 2019) disease caused by severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) has been associated with hyperinflammation induced by excessive release of a range of cytokines and chemokines. Among a plethora of cytokines, interleukin-6 (IL-6) plays a pivotal role in the immunopathology of SARS-CoV-2 infection as IL-6 has been proposed to initiate hypersecretion of cytokines by activating the Janus kinases-signal transducer and activator of transcription (JAK-STAT) pathway. Hence, targeting IL-6 and its receptor can be an appropriate therapeutic strategy to treat SARS-CoV-2 infection. However, tocilizumab (TCZ) is a well-known monoclonal antibody for its anti-inflammatory activities. TCZ has been designed to bind two different IL-6 receptors, viz., membrane-bound and soluble receptors. As an antagonist of IL-6 receptors, TCZ inhibits the JAK-STAT signaling pathway, which is essential for the transcriptional activation of cytokines-producing genes. Hence, the inhibition of IL-6 receptors can substantially reduce hyperinflammation, a key characteristic of severely infected patients with SARS-CoV-2 infection. TCZ has much promise in terms of treating SARS-CoV-2-related hyperinflammation, acute respiratory distress syndrome, and multiple organ damage. Hence, TCZ has been proposed as a potential therapeutic drug for treating COVID-19 disease. However, several discrepancies still exist, such as a well-defined molecular mechanism, efficacy, and safety parameters. In this context, various databases, including Medline, ResearchGate, PubMed, Science Direct, Scopus, and Google Scholar, were explored employing keywords such as “Cytokine storm”, “COVID-19”, “hyper inflammation”, “IL-6”, “TCZ”, and “SARS-COV-2” up to May 2021. The authors independently collected and evaluated research papers for inclusion in the current review, relying on their relatedness to the main theme of the literature review. So, this narrative review aims to provide updated information about the molecular mechanism, efficacy, and safety of TCZ in the treatment of COVID-19. However, several contradictions and challenges associated with TCZ use in the treatment of severely infected patients with COVID-19 have also been discussed.

Key words: Cytokine storm, COVID-19, hyperinflammation, interleukin-6 (IL-6), tocilizumab (TCZ), SARS-CoV-2.






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