Through putative cellular, molecular and functional mechanisms, we provide a conceptual framework on how these biological processes may interact and lead to COVID-19 severity in patients with pre-existing hypertension: the role of the RAS, inflammation, endothelial dysfunction, arterial stiffness, left ventricular hypertrophy and DPP4 are summarized in Figure 1. The gene discussed is DPP4; the disease is Hypertension.