A comprehensive review on sarilumab in COVID-19

Abstract

Introduction: The coronavirus disease 2019 (COVID-19) pandemic, caused by a newly discovered coronavirus (severe acute respiratory syndrome coronavirus 2, or SARS-CoV-2), continues to spread all around the world. Despite the emergency of COVID-19 worldwide, remdesivir is the only treatment that has been recently approved to treat the diseases, and other effective therapies are still lacking. SARS-CoV-2 may cause severe illness in 20% of patients. Based on available data, there is an association between interleukin-6 (IL-6) and severe COVID-19. Sarilumab is a fully human immunoglobulin G1 monoclonal antibody binding to both membrane-bound and soluble IL-6 receptors with high affinity and has been considered for off-label use in the treatment of COVID-19. Areas covered: The present article reviews recently published literature focusing on the pathophysiology of COVID-19 induced cytokine storm, the potential therapeutic role, and important clinical issues of sarilumab in the treatment of COVID-19 patients. Expert opinion: The off-label treatment administration is unavoidable in the critical situation of the COVID-19 pandemic. Further efforts should be directed to determine mechanisms of SARS-CoV-2 induced immune dysregulation as well as indications of sarilumab in the patients with COVID-19 to minimize concerns regarding its off-label administration.

Monoclonal antibodies for COVID-19 therapy and SARS-CoV-2 detection

“…Importantly, elevated IL-6 level has been tightly associated with ARDS and high mortality of COVID-19 patients; therefore, IL-6 is thought to be a promising therapeutic target to reduce hyper inflammation and prevent the high mortalities of COVID-19 [ 112 , 114 – 116 ]. According to the key role of IL-6 in CSS, several mAb drugs have been considered for the treatment of severe COVID-19, including sarilumab (Kevzara), tocilizumab (Actemra) and levilimab, which target IL-6R, as well as clazakizumab, siltuximab and olokizumab, which target IL-6 [ 19 , 20 , 117 , 118 ].…”

Distinctive pseudopalisaded histiocytic hyperplasia characterizes the transition of exudative to proliferative phase of diffuse alveolar damage in patients dying of COVID-19

“…[ 31 ] A further confounding factor in our conclusion is that 4 of the 5 patients with the pseudopalisaded histiocytic reaction were also treated with sarilumab a median of 20-days prior to death to manage cytokine release syndrome. [ 25 ] Sarilumab is a monoclonal antibody inhibitor of IL-6 which is produced by innate immune cells, such as monocytes/macrophages, as part of the host defense against infectious agents[ 26 ] and thus we cannot exclude that the pseudopalisaded histiocytic reaction is a result of IL-6 inhibition in these patients. It will be interesting to see if the pattern of pseudopalisaded histiocytic hyperplasia becomes less frequent in post-mortem samples following the routine use of dexamethasone rather than sarilumb in hospitalized patients requiring respiratory support.…”

Targeting tight junctions to fight against viral neuroinvasion

“…Anti-IL-6 antibodies can attenuate ischemia-related increases in endothelium permeability by modulating the expression of claudin-1 and occludin [38]. Interestingly, tocilizumab and sarilumab, two types of anti-IL-6 receptor antibodies used to treat rheumatoid arthritis and cytokine release syndrome, have recently been investigated in the context of COVID-19 [39,40]. However, biologically, IL-6 has both proinflammatory and anti-inflammatory effects and is also involved in antiviral responses, and blocking its activity may increase the chances of acquiring a secondary infection [41].…”