key: cord-0894304-4dpx35j6 authors: Lipworth, Brian; Chan, Rory; RuiWen Kuo, Chris title: COVID-19: Start with the nose date: 2020-08-14 journal: Journal of Allergy and Clinical Immunology DOI: 10.1016/j.jaci.2020.06.038 sha: 10a3d96f8c163b21326407afa9d05a51adc79e47 doc_id: 894304 cord_uid: 4dpx35j6 nan Letter to the Editor COVID-19: Start with the nose Q 1 To the Editor: We read with interest the data from Jackson et al 1 that revealed lower angiotensin-converting enzyme 2 (ACE2) expression in nasal brushings from children with allergic sensitization, along with a progressive decline in ACE2 expression in relation to increasing IgE sensitization in those with asthma. Moreover, in nasal brushings from adults with allergic rhinitis, ACE2 expression was lower after exposure to cat allergen. This may be clinically relevant because severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) enters the respiratory epithelium via an endocytic process mediated by ACE2, especially because the nose is usually the first portal of entry for viral infection. The nasopharynx is a common site for SARS-CoV-2 testing. Nasal secretions are swept by rapid nasociliary clearance into the oropharynx and thereby aspirated into the lower respiratory tract, where SARS-CoV-2 causes severe hypoxic pneumonia followed by an associated systemic cytokine-induced autoimmune hyperinflammatory response and coagulopathy. 2 Pointedly coronavirus disease-2019 (COVID-19) often presents initially with impaired smell due to involvement of the olfactory nerve endings in the nose. ACE2 expression is highest in the nose, with decreasing levels throughout the respiratory tract, which is mirrored by a gradient of SARS-CoV-2 infection along the airway epithelium. 3 The nasal expression of ACE2 also appears to be age dependent, with lower levels in children compared with adults. 4 Whether or not this might explain the higher prevalence and worse outcomes of COVID-19 in older people remains uncertain. We believe these observations may be clinically relevant when considering strategies to modify early SARS-CoV-2 infection. One possibility is to suppress replication of SARS-CoV-2 in the nose with topical delivery of antivirals, which would achieve a high local concentration. In a study of experimental coronavirus cold in healthy volunteers, the use of prophylactic treatment with intranasal IFN-a-2b resulted in shortened duration and attenuated severity of symptoms. 5 Another putative therapeutic strategy might be to use intranasal corticosteroids on a prophylactic basis. The premise is that inhaled corticosteroids are associated with dosedependent downregulation of expression of both ACE2 and TMPRSS2 Q 2 in induced sputum from patients with asthma. 6 Whether the same might occur with intranasal corticosteroids warrants further investigation. Furthermore, there is evidence of a corticosteroid-specific effect with ciclesonide and mometasone, but not fluticasone beclomethasone or budesonide, in terms of suppressing in vitro replication of SARS2-CoV-2. 7 For patients with unified allergic airways disease, this reinforces the importance of adhering to both inhaled and intranasal corticosteroid therapy, which will achieve optimal upper and lower airway disease control and may also afford protection against viral triggers including SARS-CoV-2. We also believe there is also a need to assess whether prophylactic use of intranasal corticosteroid might modify disease progression of COVID-19 in susceptible older individuals with comorbidities, including those in care homes. 1 2 3 4 5 6 7 8 9 10 11 12 13 14 15 16 17 18 19 20 21 22 23 24 25 26 27 28 29 30 31 32 33 34 35 36 37 38 39 40 41 42 43 44 45 46 47 48 49 50 51 52 53 54 55 56 57 58 59 60 Association of respiratory allergy, asthma, and expression of the SARS-CoV-2 receptor ACE2 Weathering the cytokine storm in susceptible patients with severe SARS-CoV-2 infection SARS-CoV-2 reverse genetics reveals a variable infection gradient in the respiratory tract Nasal gene expression of angiotensin-converting enzyme 2 in children and adults Prevention of experimental coronavirus colds with intranasal alpha-2b interferon COVID-19 related genes in sputum cells in asthma: relationship to demographic features and corticosteroids The inhaled corticosteroid ciclesonide blocks coronavirus RNA replication by targeting viral NSP15