According to the few studies available in the literature on the interaction of the IFN-I and TGF-β axes and the role of SERPINE1 in the induction of coagulopathy and pulmonary fibrosis, examining the expression of the involved molecules in these axes as well as their fluctuations, can open new windows to a better understanding of COVID-19 pathogenesis and emerging therapeutic approaches. This evidence concerns the gene SERPINE1 and COVID-19.