Emerging evidence has indicated that AMPK is not only a key effector of glucose and lipid metabolism, but involved in the regulation of various pathway, including: (1)Glp1r/Pka pathway and mitochondria, reducing HGP and improving insulin resistance; (2) mTOR/autophagy pathway, driving the cardiovascular protection and neuroprotection; (3)NLRP3, eNOS, STAT3, COX-2, iNOS or Smad3 pathways, mediating anti-inflammation; (4) FOX3, IRS, GCRP and PD-L1, executing anticancer; (5)cAMP pathway, improving reproductive system; (6)ACE2, probably protecting against COVID-19. This evidence concerns the gene SMAD3 and COVID-19.