The underlying mechanism is that angiotensin II binds to angiotensin II type 1 (AT1) receptor and then activates JAK/STAT signaling to induce IL-6 production.120,121 Interestingly, existing studies have shown that SARS-CoV may promote the expression of angiotensin II by downregulating ACE2,122,123 which potentially leads to the possibility that SARS-CoV-2 enhances IL-6 production via the angiotensin II/AT1 receptor/JAK/STAT axis, and the positive pro-inflammatory feedback of IL-6/JAK/STAT ultimately drives clinical signatures of COVID-19, especially COVID-CS.124. This evidence concerns the gene IL6 and Cowden syndrome 1.