An imbalance in the opposing roles of transcription factors STAT1 and STAT3 seems to operate as the central triggering event at the initial site of SARS-CoV-2 infection in the respiratory epithelium [9,10,11,12,13], resulting in catastrophic inflammatory and coagulopathy/thrombosis episodes in patients at high-risk of COVID-19 (Figure 1). Here, STAT3 is linked to COVID-19.