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Authors: Daniel J. Jackson, William W. Busse, Alkis Togias, James E. Gern, Mathew C. Altman
Journal: Journal of Allergy and Clinical Immunology (2020)

Lipworth et al1Lipworth B. Kuo C. Chan R. COVID-19: start with the nose.J Allergy Clin Immunol. 2020; 146: 1214-1215Abstract Full Text Full Text PDF PubMed Scopus (8) Google Scholar 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 al2Hou 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 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. For example, inoculation studies with rhinovirus have shown that there is often a delay of 2 to 4 days from upper to lower airway rhinovirus infection.3Gern J.E. Galagan D.M. Jarjour N.N. Dick E.C. Busse W.W. Detection of rhinovirus RNA in lower airway cells during experimentally induced infection.Am J Respir Crit Care Med. 1997; 155: 1159-1161Crossref PubMed Scopus (232) Google Scholar Collectively, these data suggest that targeting the upper airway with prophylactic strategies to prevent infection and/or therapeutic approaches in early infection to avoid progression to the lower airway hold significant promise in impacting coronavirus disease-2019 (COVID-19) susceptibility and disease outcomes. Lipworth et al suggest that intranasal corticosteroids should be tested for their ability to prevent severe COVID-19. Although intriguing in concept, data to date have been mixed on the impact of corticosteroids on COVID-19 outcomes. This is highlighted by preliminary findings in a recent study demonstrating the efficacy of dexamethasone in reducing mortality in critically ill patients with COVID-19, but showing no benefit in those not requiring respiratory support.4Horby P, Lim WS, Emberson J, Mafham M, Bell J, Linsell L, et al. Effect of dexamethasone in hospitalized patients with COVID-19: preliminary report [published online ahead of print June 22, 2020]. medRxiv. https://doi.org/10.1101/2020.06.22.20137273.Google Scholar Furthermore, our study5Jackson 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 demonstrated a "dose-response," with greater degrees of respiratory allergy being associated with larger reductions in angiotensin-converting enzyme 2 gene expression in the nasal epithelium, and the impact of suppressing type 2 inflammation in these individuals is not currently known. Thus, we agree that strategies targeting the upper airway for the prevention and/or treatment of COVID-19 are of significant interest. Studies with nasal/inhaled corticosteroids as postexposure prophylaxis for very early stages of the disease (prehospitalization) may be worth considering. Furthermore, various additional approaches are available for consideration, including topical therapy with intranasal antivirals, immune stimulants, and/or vaccines. COVID-19: Start with the noseJournal of Allergy and Clinical ImmunologyVol. 146Issue 5PreviewWe read with interest the data from Jackson et al1 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. Full-Text PDF