To point out, evidence reveals that severe cases of COVID-19 are commonly dependent on a positive feedback loop established between Signal Transducer and Activator of Transcription-3 (STAT3) and Plasminogen Activator Inhibitor-1 (PAI-1) that results in the over-stimulation of the STAT3/PAI-1 signaling network that is shared among diverse disease manifestations and leads to catastrophic consequences (157). Here, SERPINE1 is linked to COVID-19.