This pathway describes imbalances in the Renin Angiotensin System and Bradykinin pathways in COVID-19.
The expression of several genes in these pathways is affected in by SARS-CoV-2. SERPING1 is downregulated, which cancels the suppression of F12 of the intrinsic coagulation cascade, resulting in the production of bradykinin from kallikrein and KNG. ACE is downregulated, which increases bradykinin levels. ACE2 is upregulated, ACE is downregulated, which causes an increase in Angiotensin 1-9 and sensitization of bradykinin receptors. NFkappaB is suppressed by SARS-Cov-2, decreasing its binding to the ACE promoter and subsequent transcription.
The result of a hyperactive bradykinin system is vasodilation to the point of vascular leakage and infiltration of inflammatory cells.
The pathway is based on Figure 2A from [Garvin et al.](https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7410499/).