Elevated ACE 2 expression in the olfactory neuroepithelium: implications for anosmia and upper respiratory SARS CoV 2 entry and replication
The ongoing outbreak of coronavirus disease 2019 (COVID 19) caused by the severe acute respiratory syndrome coronavirus 2 (SARS CoV 2) has become a major threat to global health [1] The mechanism of cellular entry by SARS CoV 2 is through binding to angiotensin converting enzyme 2 (ACE 2) [2, 3] a metalloproteinase ectoenzyme that primarily functions in the regulation of angiotensin II, but also has non catalytic roles such as intestinal neutral amino acid transport. The level of ACE 2 protein and its subcellular localisation in the respiratory tract may be a key determinant of susceptibility to infection, symptoms and outcomes in COVID 19. In humans, ACE 2 protein is broadly expressed in the lung, kidney and small intestine [4] Pathological analysis of COVID 19 post mortem samples shows substantial damage in the lung [5] suggesting that the airway is the principal entry and target of SARS CoV 2. However, analysis of multiple single cell RNA seq datasets reveal overall low ACE 2 RNA transcription in nasal airway epithelium, with further reduced expression in lower airway club cells and rare expression in alveolar epithelial cells [6] This pattern of ACE 2 expression provides evidence that the upper, rather than the lower, airway is the initial site of SARS CoV 2 infection. ACE2 protein is expressed at high levels in the human olfactory epithelium relative to upper airway epithelial cells. This may explain COVID 19 associated olfactory dysfunction, and suggests a SARS CoV 2 reservoir site and potential intranasal therapy. https:/bit.ly/3hxT0qm
European Respiratory Journal