This pathway describes imbalances in RAS 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/).