RT Journal Article
SR Electronic
T1 Understanding olfactory dysfunction in COVID-19: Expression of ACE2, TMPRSS2 and Furin in the nose and olfactory bulb in human and mice
JF bioRxiv
FD Cold Spring Harbor Laboratory
SP 2020.05.15.097352
DO 10.1101/2020.05.15.097352
A1 Ueha, Rumi
A1 Kondo, Kenji
A1 Kagoya, Ryoji
A1 Shichino, Shigeyuki
A1 Ueha, Satoshi
A1 Yamasoba, Tatsuya
YR 2020
UL http://biorxiv.org/content/early/2020/05/21/2020.05.15.097352.abstract
AB Background Anosmia is a frequent symptom in coronavirus disease 2019 (COVID-19) patients that generally resolves within weeks. In contrast, the anosmia caused by other upper respiratory infections affects a small proportion of patients and may take months to resolve or never resolve. The mechanisms behind COVID-19-induced olfactory dysfunction remain unknown. Here, we address the unique pathophysiology of COVID-19-associated olfactory dysfunction.Methods The expression of ACE2 (virus binding receptor) and TMPRSS2 and Furin (host cell proteases facilitating virus entry) was examined in the nasal mucosa, composed of respiratory mucosa (RM), olfactory mucosa (OM), and olfactory bulb (OB) of mouse and human tissues using immunohistochemistry and gene analyses.Results Co-expression of ACE2, TMPRSS2, and Furin was observed in the RM and in the OM, especially in the supporting cells of the olfactory epithelium and the Bowman’s glands. Notably, the olfactory receptor neurons (ORNs) in the OM were positive for ACE2 but almost negative for TMPRSS2 and Furin. Cells in the OB expressed ACE2 strongly and Furin weakly, and did not express TMPRSS2. All three gene expressions were confirmed in the nasal mucosa and OB.Conclusions ACE2 was widely expressed in all tissues, whereas TMPRSS2 and Furin were expressed only in certain types of cells and were absent in the ORNs. These findings, together with clinical reports, suggest that COVID-19-related anosmia occurs mainly through sensorineural and central dysfunction and, to some extent, conductive olfactory dysfunction. The expression of ACE2, but not TMPRSS2 or Furin, in ORNs may explain the early recovery from anosmia.Competing Interest StatementThe authors have declared no competing interest.