Long-term Aspirin Therapy as a Predictor of Decreased Susceptibility to SARS-CoV-2 Infection in Aspirin-Exacerbated Respiratory Disease

AERD - Aspirin Exacerbated Respiratory Disease

Aspirin-exacerbated respiratory disease (AERD) is characterized by the presence of asthma, chronic rhinosinusitis with nasal polyposis (CRwNP), and acute respiratory reactions induced by aspirin and other cyclooxygenase-1 inhibitors. One of the well-established therapeutic options is aspirin desensitization followed by daily aspirin therapy. The potential mechanisms underlying the clinical benefit of this approach include the downregulation of CysLT1 receptor, inhibition of PGD2 and interleukin IL-4 via the signal transducer and activator of transcription 6, global (blood, urine) activation of type 2 (T2) inflammation as well as local (sputum) reduction of T2 asthma inflammation. Indeed, among current aspirin-treated patients with AERD (n=37), no one had severe acute respiratory syndrome coronavirus clade 2 (SARS CoV-2) infection and most importantly, none of them developed COVID19 during pandemic. WHY? Notably, patients with AERD did not have asthma and nasal polyps exacerbation on aspirin, which is in line with other studies. Respiratory infections, such as the current COVID-19 pandemic, target epithelial cells in the respiratory tract. SARS-CoV-2 spike (S) protein binds angiotensin-converting enzyme 2 (ACE2), and in concert with host proteases, principally transmembrane serine protease 2 (TMPRSS2), promotes cellular entry. Nasal and bronchial epithelium play a key role in the early phases of an immune response to respiratory viruses. Induced sputum (IS) and nasal lavage (NL) cells are likely the first immune cells to encounter SARS CoV-2 during an infection, and their reaction to the virus will have a profound impact on the outcome of the infection. Interferons (IFNs) are antiviral cytokines and among the first mediators produced upon viral infection. IFNs are divided into three groups based on their receptor usage; type I IFNs (IFN-α and IFN-β), type II IFN (IFN-γ), and type III IFNs (IFN-λ1 and 2). Both production of IFN and cellular response to IFN are critical steps for the restriction of viral dissemination. An interferon-stimulated gene (ISG) is a gene whose expression is stimulated by interferon. Specifically, type I and type III interferons are antiviral cytokines, triggering ISGs that combat viral infections. The type II interferon class only has one cytokine (IFN-γ), which has some antiviral activity. To conclude, the assessment of gene expression for interferon α1 (IFNA1), interferon β1 (IFNB1), interferon γ (IFNG), interferon λ1 and λ2 (IFNL1 and IFNL2) as well as for ACE2 and TMPRSS2 in sputum and nasal cells may shed new light on the course of this infection in patient with AERD during long term aspirin therapy.

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