Therapeutic Impact of Tocilizumab in the Setting of Severe COVID-19; an Updated and Comprehensive Review on Current Evidence

Abstract

Introduction: The COVID-19 pandemic caused by SARS-CoV-2 has been the major health concern in 2019 globally. Considering the severity and phase of the disease, various pharmacotherapy schedules were proposed. Here, we set out to provide close-up insights on the clinical utility of Tocilizumab (TCZ), a biologic monoclonal antibody in this regard.

Methods: In this comprehensive review, various databases, including Scopus, PubMed Central, Medline, Embase, Google Scholar, and preprint publishers (med/bioRxiv) were searched until January 30, 2024, according to the keywords and search criteria.

Results: Besides the pros and cons, compelling evidence purported the safety and efficacy of TCZ and indicated that it exhibits great potential to reduce short-term and all-cause (28-30-day) mortality. TCZ significantly drops the adverse events if administered in the right time course (in the inflammatory phase) during critical/severe COVID-19 pneumonia. Despite contradictory results, the benefits of TCZ appear significant, especially in combination with add-on therapies, such as corticosteroids. Although the safety of TCZ is acceptable, solid data is lacking as to its benefits during pregnancy. There are limited data on TCZ combination therapies, such as hemoperfusion, intravenous immunoglobulin (IVIG), simple O2 therapy, vasopressor support, convalescent plasma therapy, and even in vaccinated patients and COVID-19 reinfection, especially in elderly persons. In addition, the impact of TCZ therapy on the long-lasting COVID-19 is unclear.

Conclusion: Personalized medicine based on individual characteristics and pertinent clinical conditions must be considered in the clinicians' decision-making policy. Finally, to mitigate the risk-to-benefit ratio of TCZ, a treatment algorithm, based on available literature and updated national institute of health (NIH) and Infectious Diseases Society of America (IDSA) guidelines, is also proposed.

Keywords: Algorithms; COVID-19; COVID-19 drug treatment; SARS-CoV-2; Tocilizumab; Treatment outcome.

Figure 1

Tocilizumab (TCZ) mechanism of action in patients with severe COVID-19. Following the Acute respiratory distress syndrome (ARDS) induced by SARS-CoV-2, the robust release of pro-inflammatory cytokines, named cytokine storm, can occur, which subsequently worsens the patients’ clinical symptoms. During the inflammatory phase, IV infusion of the anti-IL6 agent, TCZ, by blocking IL-6 both soluble (sIL-6) and membrane (mIL-6) receptors, can remarkably alleviate cytokine release syndrome (CRS)-related adverse events. The figure was created with BioRender.com.

Figure 2

Study selection process based on PRISMA flow diagram. Preferred reporting items for systematic reviews and meta‐analyses (PRISMA) and the review criteria details are described in the Methods section.

Figure 3

The Clinical improvement following Tocilizumab (TCZ) therapy in patients with severe COVID-19. The figure was created with BioRender.com. CRS: cytokine release syndrome; ICU: intensive care unit; MV: mechanical ventilation.

Figure 4

Recommendations Tocilizumab (TCZ) administration in patients with confirmed COVID-19 based on available data and guidelines. Created with BioRender.com. Abbreviations: CT: computed tomography; CRP: C-reactive Protein; ECMO: Extracorporeal Membrane Oxygenation; IVIG: Intravenous immunoglobulin; HFNC oxygen: high-flow nasal cannula oxygen; IDSA: The Infectious Diseases Society of America; IV: Intravenous; MV: Mechanical Ventilation; NIH: National Institutes of Health; NIV: Non-Invasive Ventilation; TCZ: Tocilizumab; ULN: upper limit normal. The figure was created with BioRender.com.