Table 1.

Explanation of distinct COVID19 signs and symptoms by the proposed theory of Bradykinin/Nitric Oxide pathway.

COVID19 distinct findings	Explanation by proposed hypothesis
Dry cough	Increase in BRK activity
Oxygen saturation drop	1.Increase in BRK activity, diffuse endothelial NO synthesis and subsequent methemoglobinemia 2.Increase in BRK activity, bronchospasm and vascular leakage syndrome due to BRK synthesis, Ventilation perfusion mismatch
Coagulopathy	Increased BRK activity occupying Kallikrein activity. This may result in distraction of functional capacity of Kallikrein from its parallel role in coagulation cascade
Ameliorating effect of Zinc supplement	The backdoor pathway of BRK inactivation are amino-peptidase and carboxypeptidase both having a Zinc core limited by availability of total body Zinc reserve
Prevalence in hypertensive patients	ACE gene polymorphisms produce less active and less abundant enzyme which in turn is better exhausted out of capacity, therefore increasing BRK
Deleterious effect of ACEIs like Captopril, Lisinopril	ACEI decreases ACE function that is already weak due to SARS-CoV-2(as explained in the text). As a result active BRK increases
ARB less detrimental and even protective	Causes an compensatory increase in ACE activity (after previous chronic use) which in turn neutralize BRK into inactive forms
Reported effect of NO aerosol	It conjugates the NO in the lung making Dinitrogen dioxide which is exhaled by expiration. Therefore NO is eliminated from the whole body as an exhaust
A smooth prodrome of a weak or so and a rapid flare up afterwards	Amino-peptidase enzyme keeps BRK tissue level low till it runs out of Zinc supply and at that time a burst of BRK trigger all other inflammatory agents-the so called-cytokine storm. White lungs happen due to massive vascular leakage
Disorder of taste and smell	Has been ascribed to increased BRK activity as a side effect of ACEI confirming the BRK role in this symptom
Diarrhea	Carboxypeptidase is recruited for BRK inactivation. It is also an important intestinal brush border enzyme which may fail this important function in this setting

ACE: Angiotensin Converting Enzyme, ACEI:Angiotensin Converting Enzyme Inhibitor, ARB: Angiotensin2 Receptor Blocker, BRK: Bradykinin, NO: Nitric Oxide.