Combined IL-6 and JAK/STAT inhibition therapy in COVID-19-related sHLH, potential game changer.

Abstract

Coronavirus disease 2019 (COVID-19), caused by novel SARS-CoV-2, leads to significant mortality and morbidity with increasing evidence for inflammatory pathways being implicated in the lung damage it causes. (1,2) Severe COVID-19 patients present with increased inflammatory markers, akin to secondary haemophagocytic lymphohistiocytosis (sHLH), that have been shown to predict mortality. (3,4) There is emerging evidence for the use of an interleukin 6 (IL-6) inhibitor, tocilizumab (TCZ), for suppression of the inflammatory cytokine storm in this context. (5-7) Ruxolitinib (RXB), a JAK-STAT inhibitor, has also been shown to have proven efficacy in the treatment of sHLH. (8) Both agents appear to be promising in the fight against SARS-CoV-2 infection, (9,10) leading to an increasing number of trials being registered with their use. (11,12) Until this point, no single agent has shown a survival benefit against SARS-CoV-2 and it is possible that monotherapy may not suppress inflammation enough to overcome the COVID-19 related cytokine storm and hyper-inflammation.