Fig. 2.
The central role of ACE 2 in SARS-CoV-2 infection and COVID-19 severity. Exposure to air pollutants like cigarette smoke and PM2.5 increases ACE2 expression (1) notably in upper and lower airway epithelial cells, providing more opportunities for SARS-CoV-2 binding [2]. SARS-CoV-2 fusion glycoproteins forming the spikes require cleaving by an endogenous protease like transmembrane protease serine type 2 (TMPRSS2) in order to optimally bind to its receptor ACE2 and be internalized for replication [3]. The decreased surface expression of ACE2 limits the amount of Angiotensin II that is cleaved by ACE2 into Ang1-7. This decrease in Ang1-7 signaling through its G couple receptor MAS in favor of the pro-inflammatory AngII/AT1R pathway likely contributes to COVID-19 disease pathogenesis