Chronic use of aspirin as a prognostic factor for reduced susceptibility to SARS-CoV-2 virus infection in aspirin-exacerbated respiratory disease

Respiratory disease with exacerbation of aspirin (AERD) is characterized by the presence of asthma, chronic rhinitis and sinusitis with nasal polyposis (CRwNP) and acute respiratory reactions induced by aspirin and other inhibitors cyclooxygenase-1. Desensitization to aspirin followed by daily use of aspirin is an effective treatment for aggravated respiratory disease by aspirin (AERD). In aspirin treated patients with AERD, it has been observed that they do not develop the coronavirus group 2 (SARS-CoV-2) or develop the disease (COVID19). There is an urgent need understanding the pathogenesis of SARS-CoV-2 that causes COVID-19. SARSCoV-2 spike (S) protein binds angiotensin-converting enzyme 2 (ACE2) and together with proteases the host, primarily through membrane serine protease 2 (TMPRSS2), aids entry into cells. ACE2 and TMPRSS2 are co-expressed in airway and cell epithelium sputum, while CD147 (BSG) and CD26 (DPP4) are expressed in both epithelium and immune cells. In several human studies it has been found increasing the level of gene expression for interferon (ISG) in displaying cells ACE2 expression. An increase in ACE2 levels in cells has also been observed bronchi treated with type I or II interferon. Our goal is to determine whether or not treatment aspirin, which inhibits the enzyme cyclooxygenase-1, can serve as a predictor of decreased susceptibility to SARS-CoV-2 infection and COVID-19 disease in AERD. We also undertake an attempt to assess genetic characteristics that may predict or attenuate SARS-CoV2 infection during treatment with high doses of aspirin. We're going to evaluate gene expression for interferons, known SARS-CoV-2 receptors, and other transcriptomes of 96 genes in sputum and nasal cells, and assess the relationship between this expression and long-term therapy high-dose aspirin in patients with AERD. We hypothesized that it was long-term high-dose aspirin therapy leads to a reduction in the expression of the ACE2 receptor and the gene stimulated by interferon (ISG) in sputum and nasal cells in patients with AERD. Such the effects were previously described with inhaled corticosteroids in asthma. We speculate that aspirin causes even lower expression of ACE2, TMPRSS2, CD147 (BSG) and CD26 (DPP4) in sputum and nasal cells. In addition, we assumed that aspirin could affect the expression of interferons α1 (IFNA1), β1 (IFNB1), γ (IFNG), as well as λ1 and λ2 (IFNL1 and IFNL2). Our preliminary studies showed differences in the expression of interferon genes in sputum cells between healthy (n = 13) and AERD patients (n = 26)