Targeting JAK-STAT Signaling to Control Cytokine Release Syndrome in COVID-19

Recent advances in the pathophysiologic understanding of the severe acute re- spiratory syndrome coronavirus 2 (SARS-CoV-2) infection has indicated that pa- tients with severe coronavirus disease 2019 (COVID-19) might experience cytokine release syndrome (CRS), characterized by increased interleukin (IL) -6, IL -2, IL -7, IL -10, etc. Therefore, the treatment of cytokine storm has been pro- posed as a critical part of rescuing severe COVID-19. Several of the cytokines in- volved in COVID-19 employ a distinct intracellular signaling pathway mediated by Janus kinases (JAKs). JAK inhibition, therefore, presents an attractive thera- peutic strategy for CRS, which is a common cause of adverse clinical outcomes in COVID-19. Below, we review the possibilities and challenges of targeting the in COVID-19.