Importantly, the unique behavior of silibinin as a bimodal SH2- and DBD-STAT3 transcription factor inhibitor in vitro, in situ, and in vivo [28,36] largely explains its ability to fully prevent the hyper-activation of STAT3 imposed by the excessive production of IL-6, a key driver of the dysregulated inflammation in patients suffering from severe COVID-19. This evidence concerns the gene IL6 and COVID-19.