Cytokine-Induced Modulation of SARS-CoV2 Receptor Expression in Primary Human Nasal Epithelial Cells

Background: Viral entry of severe acute respiratory syndrome coronavirus 2 (SARS-CoV2) via the spike protein enables endocytosis into host cells using the ACE2 receptor and TMPRSS2. The frequent upper respiratory tract symptoms of COVID-19 and the localization of the virus to the nasopharynx, the most common site of swabbing, indicate that the sinonasal mucosa may play an important role in SARS-CoV2 infection and viral replication. Methods: This paper investigates the presence of ACE2 receptor and TMPRESS2 expression in the primary human nasal epithelial cells (HNECs) from the following: chronic rhinosinusitis without nasal polyps (CRSsNP), CRS with nasal polyps (CRSwNP) and control (non-CRS) patients, and maps the expression changes when exposed to Th1, Th2, Th17-associated cytokines. Results: We found that ACE2 and TMPRSS2 expression was higher in control HNECs than CRSwNP HNECs, and that both ACE2 and TMPRSS2 were downregulated further by Th2 cytokines in CRSwNP HNECs. Conclusions: This indicates an immune dysregulated state of CRSwNP mucosa, which normally contributes to a chronic inflammatory state, and might support an altered susceptibility to SARS-CoV2 infection and transmission.

Automated summary

The study found that ACE2 and TMPRSS2 expression in nasal epithelial cells of patients with chronic rhinosinusitis with nasal polyps was lower than in the control group, and was further downregulated after exposure to Th2 cytokines. This suggests that patients may have an immune dysregulated state, altering susceptibility to SARS-CoV-2 infection and transmission.