Asthma and viruses: A focus on rhinoviruses and SARS-CoV-2

• Published in: Journal of allergy and clinical immunology Vol. 147; no. 5; pp. 1648 - 1651
• Main Authors: Padayachee, Yorissa, Faiez, Tasnim Shahridan, Singanayagam, Aran, Mallia, Patrick, Johnston, Sebastian Lennox
• Format: Journal Article
• Language: English
• Published: United States Elsevier Inc 01.05.2021; Elsevier Limited; Published by Elsevier Inc. on behalf of the American Academy of Allergy, Asthma & Immunology
• Subjects: Alveoli; Angiotensin; Antiviral activity; Antiviral drugs; Asthma; Asthma - complications; Asthma - immunology; asthma exacerbation; Bronchus; Clinical trials; Coronaviridae; Coronaviruses; Corticosteroids; COVID-19; COVID-19 - etiology; COVID-19 - immunology; CXCL10 protein; CXCL11 protein; Dendritic cells; Epithelial cells; Gene expression; Humans; Innate immunity; interferons; Interleukin 15; Lavage; Mortality; Mucosa; Pandemics; Patients; Peptidyl-dipeptidase A; Picornaviridae Infections - etiology; Picornaviridae Infections - immunology; Respiratory tract diseases; Rhinovirus; Rhinovirus - immunology; rhinoviruses; Risk factors; SARS-CoV-2 - immunology; Severe acute respiratory syndrome coronavirus 2; Transcriptomes; Viruses; α-Interferon; β-Interferon; γ-Interferon; United Kingdom > UK; COVID-19; rhinoviruses; asthma exacerbation; asthma; interferons; Severe acute respiratory syndrome coronavirus-2
• ISSN: 0091-6749; 1097-6825; 1097-6825
• DOI: 10.1016/j.jaci.2021.03.011

Here, we review the role played by viruses in AEs and the role of asthma in the risk of severe outcomes in coronavirus disease 2019 (COVID-19).Interferon impairment in people with asthma Interferons (IFNs) are critical components of innate immune response and are a robust first line of defense against viruses. Ex vivo studies in cells from people with asthma showed delay and impairment in production of IFN-α, IFN-β, IFN-γ, and IFN-λ in bronchoalveolar lavage cells, PBMCs, dendritic cells (DCs), and human bronchial epithelial cells (HBECs) in response to infection with RVs and other respiratory viruses.3 The importance of IFN impairment in AE pathogenesis is strongly supported by a study showing that IFN impairment at baseline is strongly related to symptom severity, airway inflammation, and viral load in subsequent experimental virus-induced AEs.3 An elegant study applying transcriptome network analysis, in children with asthma, also demonstrated that a low type-1 IFN response at baseline was a robust predictor of short-term AE risk.1 The same study reported a “type-1 IFN response” module, which contained numerous antiviral effector molecules, was upregulated in nasal and blood samples during virus-induced AEs, and suggested that low IFN signaling at baseline enhances viral replication during early infection, which secondarily induces an exaggerated IFN response later during exacerbation.1 This interpretation is supported by a study reporting an approximately 250-fold increase in nasal lavage virus load in people with asthma compared with healthy subjects, on day 3 following RV experimental infection2 followed by subsequent increased nasal mucosal lining fluid levels of IFN-γ and the IFN-stimulated-genes CXCL11/ITAC, CXCL10/IP10, and IL-15, at later time points.4 Clinical trials of inhaled IFN-β have shown attenuation of cold-induced worsening of peak flow and of asthma symptoms5 in people with moderate/severe asthma, but neither study was large enough to include AE frequency as an outcome. [...]studies on AZM antiviral activity and on its efficacy in AEs are clearly warranted.Asthma as a risk factor for severe acute respiratory syndrome coronavirus-2 infection Severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2), the virus responsible for the COVID-19 pandemic, infects the upper and lower respiratory tracts, entering host cells through the angiotensin-converting-enzyme-2 receptor and the protease TMPRSS-2.7 The World Health Organization highlighted that people with severe asthma are a high-risk group for SARS-CoV-2 infection, and COVID-19 severity, and advocated stringent shielding of these individuals. [...]patients with asthma on high-dose inhaled corticosteroids had increased COVID-19 mortality risk compared with those on short-acting beta-agonists only.8 However, OpenSAFELY is a retrospective observational study using general practitioner records to define asthma, which may reveal potential associations but cannot define causal relationships.8 Furthermore, the study could not expand on other underlying disease characteristics that may not be captured in primary health care records, which may reveal individuals with an increased susceptibility to viral infections as well as more severe asthma.8 The International Severe Acute Respiratory and emerging Infection Consortium analyzed more than 75,000 UK COVID-19 hospital admissions and reported that patients 16 years and older, with asthma of any severity, were significantly more likely than patients without asthma to receive critical care.