COVID-19: Start with the nose
Authors: Brian Lipworth, Rory Chan, Chris RuiWen Kuo
Journal: Journal of Allergy and Clinical Immunology (2020)

We read with interest the data from Jackson et al1Jackson D.J. Busse W.W. Bacharier L.B. Kattan M. O'Connor G.T. Wood R.A. et al.Association of respiratory allergy, asthma, and expression of the SARS-CoV-2 receptor ACE2.J Allergy Clin Immunol. 2020; 146: 203-206.e3Abstract Full Text Full Text PDF PubMed Scopus (426) Google Scholar 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.2Lipworth B. Chan R. Lipworth S. RuiWen Kuo C. Weathering the cytokine storm in susceptible patients with severe SARS-CoV-2 infection.J Allergy Clin Immunol Pract. 2020; 8: 1798-1801Abstract Full Text Full Text PDF PubMed Scopus (37) Google Scholar 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.3Hou Y.J. Okuda K. Edwards C.E. Martinez D.R. Asakura T. Dinnon III, K.H. et al.SARS-CoV-2 reverse genetics reveals a variable infection gradient in the respiratory tract.cell. 2020; 182: 429-446.e14Abstract Full Text Full Text PDF PubMed Scopus (999) Google Scholar The nasal expression of ACE2 also appears to be age dependent, with lower levels in children compared with adults.4Bunyavanich S. Do A. Vicencio A. Nasal gene expression of angiotensin-converting enzyme 2 in children and adults.JAMA. 2020; 323: 2427-2429Crossref PubMed Scopus (588) Google Scholar 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-α-2b resulted in shortened duration and attenuated severity of symptoms.5Turner R.B. Felton A. Kosak K. Kelsey D.K. Meschievitz C.K. Prevention of experimental coronavirus colds with intranasal alpha-2b interferon.J Infect Dis. 1986; 154: 443-447Crossref PubMed Scopus (69) Google Scholar Another putative therapeutic strategy might be to use intranasal corticosteroids on a prophylactic basis. The premise is that inhaled corticosteroids are associated with dose-dependent downregulation of expression of both ACE2 and transmembrane protease, serine 2 in induced sputum from patients with asthma.6Peters M.C. Sajuthi S. Deford P. Christenson S. Rios C.L. Montgomery M.T. et al.COVID-19 related genes in sputum cells in asthma: relationship to demographic features and corticosteroids.Am J Respir Crit Care Med. 2020; 202: 83-90Crossref PubMed Scopus (354) Google Scholar 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-2.7Matsuyama S, Kawase M, Nao N, Shirato K, Ujike M, Kamitani W, et al. The inhaled corticosteroid ciclesonide blocks coronavirus RNA replication by targeting viral NSP15 [published online ahead of print March 12, 2020]. bioRxiv. https://doi.org/10.1101/2020.03.11.987016.Google Scholar 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. Association of respiratory allergy, asthma, and expression of the SARS-CoV-2 receptor ACE2Journal of Allergy and Clinical ImmunologyVol. 146Issue 1PreviewThe novel coronavirus SARS-CoV-2 (COVID-19) was recognized in December 2019 as a cause of severe pneumonia and has now led to a global pandemic.1 Respiratory illnesses caused by COVID-19 cover a range of severity. The identification of risk and protective factors for disease severity from COVID-19 is critical to direct development of new treatments and infection prevention strategies. Early large case series have identified a number of risk factors for severe disease, including older age, hypertension, diabetes, cardiovascular disease, tobacco exposure, and chronic obstructive pulmonary disease. Full-Text PDF ReplyJournal of Allergy and Clinical ImmunologyVol. 146Issue 5PreviewLipworth et al1 raise interesting and important concepts related to the central role that the nose plays in susceptibility to respiratory viruses, such as severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). The nasal epithelium is the initial target for SARS-CoV-2 infections, and Hou et al2 recently demonstrated greater angiotensin-converting enzyme 2 expression and an associated enhanced susceptibility to SARS-CoV-2 infection in upper versus lower airway cells. Furthermore, a progression of infection from the upper to lower airway has been clearly demonstrated for other respiratory viruses. Full-Text PDF