Gene expression profiles of nasal epithelium in long COVID

The nasal epithelium(NE) is the primary site of infection for SARS-CoV-2, however little is known about its role in long COVID(LC). Therefore, this study aimed to investigate its biological profiles to unravel pathophysiological mechanisms of LC. Medical data and NE were collected from LC patients at 3-6 and 12-18 months post-COVID. Transcriptomes were explored using hierarchical clustering to identify transcriptomic and cellular clusters. Patients with and without pulmonary radiological abnormalities(PRA) were compared using a supervised approach. CRISPR-Cas9 gene-editing was used for functional validation. Transcriptomic (n=2) and cellular (n=2) clusters of NE were identified and related to inflammation and ciliogenesis (padj<0.05). In patients with PRA, SMURF1 was significantly upregulated. SMURF1-/- mutant NE cells showed significantly decreased inflammatory cytokine production upon viral stimulation. Concluding, inflammatory profiles of NE were found in LC. This study shows the need to further assess and validate SMURF1 for the disease management of LC. Overall design: To understand molecular underpinning of long COVID we analyzed the nasal epithelial transcriptomes of long COVID patients at 3-6 months and 12-18 months post-infection