Aspirin-exacerbated respiratory disease (AERD) is characterized by the presence ofasthma, chronic rhinosinusitis with nasal polyposis (CRwNP), and acute respiratoryreactions induced by aspirin and other cyclooxygenase-1 inhibitors. One of thewell-established therapeutic options is aspirin desensitization followed by daily aspirintherapy. The potential mechanisms underlying the clinical benefit of this approachinclude the downregulation of CysLT1 receptor, inhibition of PGD2 and interleukin IL-4via 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 asthmainflammation. Indeed, among current aspirin-treated patients with AERD (n=37), no one hadsevere acute respiratory syndrome coronavirus clade 2 (SARS CoV-2) infection and mostimportantly, none of them developed COVID19 during pandemic. WHY? Notably, patients withAERD did not have asthma and nasal polyps exacerbation on aspirin, which is in line withother studies. Respiratory infections, such as the current COVID-19 pandemic, targetepithelial cells in the respiratory tract. SARS-CoV-2 spike (S) protein bindsangiotensin-converting enzyme 2 (ACE2), and in concert with host proteases, principallytransmembrane serine protease 2 (TMPRSS2), promotes cellular entry. Nasal and bronchialepithelium play a key role in the early phases of an immune response to respiratoryviruses. Induced sputum (IS) and nasal lavage (NL) cells are likely the first immunecells to encounter SARS CoV-2 during an infection, and their reaction to the virus willhave a profound impact on the outcome of the infection. Interferons (IFNs) are antiviralcytokines and among the first mediators produced upon viral infection. IFNs are dividedinto three groups based on their receptor usage; type I IFNs (IFN-α and IFN-β), type IIIFN (IFN-γ), and type III IFNs (IFN-λ1 and 2). Both production of IFN and cellularresponse to IFN are critical steps for the restriction of viral dissemination. Aninterferon-stimulated gene (ISG) is a gene whose expression is stimulated by interferon.Specifically, type I and type III interferons are antiviral cytokines, triggering ISGsthat 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 forinterferon 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 newlight on the course of this infection in patient with AERD during long term aspirintherapy.