Is Covid-19 Severity Associated With ACE2 Degradation?

Covid-19 is particularly mild with children, and its severity escalates age. Several theories have been proposed to explain these facts. In particular, it was that the lower expression of viral receptor ACE2 in children protects them from severe Covid-19. However, other works suggested an inverse relationship between disease severity. Here we review seemingly contradicting observations on at levels mRNA, membrane protein serum humans rodents try reconcile light Renin-Angiotensin system (RAS) bradykinin system, which constitute integrated inflammatory connected by common peptidases interacting receptors. We find level not monotonically related age but reaches a maximum young depends cell type then decreases, consistently almost all existing data. The increase protease Tumor necrosis factor alpha (TNF- ? ) converting enzyme (TACE), also known as ADAM17 (a disintegrin metalloproteinase 17) sheds predicts decrease occurs before steeper for than mRNA. This negative relation old paradoxical consistent mathematical model higher does necessarily favour virus propagation can even slow down. More importantly, angiotensin-bradykinin characterized powerful positive feedback loop enhances inflammation through Angiotensin Bradykinin receptors upregulate ADAM17, turn downregulates upregulates TNF- pro-inflammatory cytokine interleukin 6 (IL6). propose contributes essentially reverse this state downregulating peptides failure do this, possibly induced degradation SARS-COV-2, may underlie both CoViD-19 infection many post-infection manifestations, including multi-inflammatory syndrome (MIS-C). Within view, despite be their alternative angiotensin II ATR2 general anti-inflammatory arm RAS