Interleukin-6 Antagonists: Lessons From Cytokine Release Syndrome to the Therapeutic Application in Severe COVID-19 Infection

Abstract

Current retrospective data have found up to 20% of COVID-19 infection had developed into severe cases with hyperinflammatory pulmonary symptoms. Interleukin 6 (IL-6) is recognized as a key mediator of hyperinflammation previously mentioned in cytokine release syndrome. This leads to implementing IL-6 pathway inhibition in severe COVID-19. This review aimed to explore the clinical evidences of using IL-6 antagonists in COVID-19 infection based on most recent available data. Relevant studies were searched through PubMed, scopus, and ISI databases focusing on interleukin-6 antagonists in cytokine release syndrome and prospective data on COVID-19 infection. Only papers in English were included in the search. There were several studies conducted to evaluate the potential efficacy and safety of IL-6 antagonists and mostly with tocilizumab. After the search, we found that studies recruited patients with severe COVID-19 and elevated inflammatory mediators such as C-reactive protein (CRP), IL-6, or ferritin to receive tocilizumab, situximab or sarilumab in combination with other medications. Result showed that these agents may provide a clinical advantage as patients were able to refrain from invasive ventilation support after initiating IL-6 antagonists. In summary, IL-6 pathway inhibition in severe COVID-19 may be an emerging candidate to subside pulmonary complication. These agents may carry benefits in COVID-19 infection as well as safety risks such as bone marrow suppression. Current pharmacists’ role is to provide most recent update information as well as intensive monitoring plan in patients who receive IL-6 inhibitor. However, robust clinical evidences are warranted to confirm efficacy and safety of IL-6 antagonists.