Furthermore, high circulating levels of IL-6 as in a COVID-19-associated cytokine storm result in trans-signaling allowing IL-6 together with sIL-6Rα to activate cells not expressing the membrane-bound IL-6R, like endothelial cells.25 As a result of the IL-6-mediated activation, E-cadherin expression is reduced on endothelial cells leading to vascular hyperpermeability. This evidence concerns the gene IL6R and COVID-19.