25.04.2020
SARS-CoV-2 entry factors are highly expressed in nasal epithelial cells together with innate immune genes
Others TransversalImmunity
Sungnak W et al
Nature Med
Main result
It is known that nasal swabs are more sensitive to detected SARS-COV- viral load compared to throat swabs. The nasal epithelium is likely the gateway for entry for the virus via mainly the link between the spike protein (S) and the ACE2 receptor. Binding affinity has been shown to be a major determinant of the rate of replication of SARS-CoV and the severity of the disease.
The authors found here that, despite a low level of overall expression, ACE 2 was expressed in several types of epithelial cells in the respiratory tract (especially nasal epithelial cells), as well as in alveolar epithelial cells.
Two clusters of goblet cells and a cluster of ciliated cells had the highest levels of these receptors among all the studied cell types. The higher expression of ACE 2 in the nasal epithelial cells was confirmed with the highest expression of ACE 2 being within the secretory nasal cells and the ciliated cells.
The expression of transcripts associated with viral entry outlined their enrichment in respiratory, corneal, and intestinal epithelial cells, explaining the high transmission rates of SARS-CoV-2. These genes are co-expressed in nasal epithelial cells with genes involved in innate immunity, highlighting the potential role of nasal cells in the initiation of the infection, its spread, and clearance.
The authors found here that, despite a low level of overall expression, ACE 2 was expressed in several types of epithelial cells in the respiratory tract (especially nasal epithelial cells), as well as in alveolar epithelial cells.
Two clusters of goblet cells and a cluster of ciliated cells had the highest levels of these receptors among all the studied cell types. The higher expression of ACE 2 in the nasal epithelial cells was confirmed with the highest expression of ACE 2 being within the secretory nasal cells and the ciliated cells.
The expression of transcripts associated with viral entry outlined their enrichment in respiratory, corneal, and intestinal epithelial cells, explaining the high transmission rates of SARS-CoV-2. These genes are co-expressed in nasal epithelial cells with genes involved in innate immunity, highlighting the potential role of nasal cells in the initiation of the infection, its spread, and clearance.
Takeaways
ACE2, the entrance receptor for SARS-CoV-2, and the protease TMPRSS2 associated with the viral entry were strongly expressed in the nasal cavities (epithelium) and the ciliated cells.
This discovery implies that nasal cells may be the source of the virus's entry and may be possible reservoirs for dissemination within the body or between individuals.
Co-expression of these two in the esophagus, ileum and colon could explain clinically observed fecal viral shedding, with implications for potential fecal-oral transmission, while co-expression in superficial conjunctival cells could explain an ocular phenotype observed in some COVID-19 patients with spread through the nasolacrimal duct.
This discovery implies that nasal cells may be the source of the virus's entry and may be possible reservoirs for dissemination within the body or between individuals.
Co-expression of these two in the esophagus, ileum and colon could explain clinically observed fecal viral shedding, with implications for potential fecal-oral transmission, while co-expression in superficial conjunctival cells could explain an ocular phenotype observed in some COVID-19 patients with spread through the nasolacrimal duct.
Strength of evidence Moderate
- Experimental study well done with healthy tissue samples
- Lack of data on tissues infected with SARS-CoV-2
- Study still preliminary"
Objectives
Assessment of the potential tropism of SARS-CoV-2 by studying the expression of genes associated with viral entry in RNA sequencing data from several healthy human tissues.
Method
Experimental study on tissues from healthy human donors
To further characterize the specific types of epithelial cells expressing ACE2, the authors evaluated the expression of ACE2 in the pulmonary epithelium and the respiratory tract.
To further characterize the specific types of epithelial cells expressing ACE2, the authors evaluated the expression of ACE2 in the pulmonary epithelium and the respiratory tract.
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