Gene Expression Profiling of SARS-CoV-2 Host Entry Factors in Nasal and Oral Cavities: Evidence from Hospitalized COVID-19 Patients.

SARS-CoV-2 entry into host cells relies on key proteins like ACE2, TMPRSS2, FURIN, and CTSL, yet data remain limited regarding their expression across nasal and oral cavities within the same individual. Understanding this distribution is therefore crucial for insights into viral pathogenesis and transmission. To address this gap, nasopharyngeal, lingual, sublingual, and saliva samples were collected from 21 hospitalized COVID-19 patients; expression levels of ACE2, TMPRSS2, FURIN, CTSL, and SARS-CoV-2 genes ORF1ab and N were analyzed using real-time PCR, with viral and host gene expression normalized to GAPDH. Correlation analysis assessed the relationships between viral and host gene expressions. Nasopharyngeal swabs showed the highest positivity (100%) for viral genes and the lowest Ct values, indicating the highest viral load. These samples also had the highest expression of all four host mediators. In contrast, lingual and sublingual samples had significantly lower viral detection and gene expression, while saliva showed intermediate sensitivity (66.6-71.4%). Spearman correlation revealed strong positive associations between ACE2, TMPRSS2, FURIN, and viral genes in nasopharyngeal samples, highlighting their role in viral entry and replication, whereas CTSL showed minimal correlation. These findings identify the nasopharynx as the primary site for SARS-CoV-2 entry and replication, highlight the diagnostic value of nasal specimens, and provide insights into potential therapeutic targets and strategies to prevent viral transmission and manage future outbreaks.