ACE2 and COVID-19: SARS-CoV-1 and SARS-CoV-2 having direct and indirect binding to TLR-4, together with other viral precedents, which when combined shed light on the COVID-19 pathophysiological puzzle and the SARS-CoV-2 spike glycoprotein binds TLR-4 and activates TLR-4 signaling to increase cell surface expression of ACE2 facilitating entry [50].