TY - JOUR T1 - Elevated ACE2 expression in the olfactory neuroepithelium: implications for anosmia and upper respiratory SARS-CoV-2 entry and replication JF - European Respiratory Journal JO - Eur Respir J DO - 10.1183/13993003.01948-2020 SP - 2001948 AU - Mengfei Chen AU - Wenjuan Shen AU - Nicholas R. Rowan AU - Heather Kulaga AU - Alexander Hillel AU - Murugappan Ramanathan, Jr AU - Andrew P. Lane Y1 - 2020/01/01 UR - http://erj.ersjournals.com/content/early/2020/07/23/13993003.01948-2020.abstract N2 - 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 (ACE2) [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 ACE2 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, ACE2 protein is broadly expressed in the lung, kidney, and small intestine [4]. Pathological analysis of COVID-19 postmortem 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 ACE2 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 ACE2 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, while suggesting a SARS-CoV-2 reservoir site and potential intranasal therapy. ER -