Multi-tissue genetic analysis suggests SARS-CoV-2 may infect specific nose cells

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Genes associated with how the virus SARS-CoV-2 enters a host were found to be expressed in specific healthy human respiratory, corneal and intestinal epithelial cells, according to a study. Expression of these genes was observed in nasal cells alongside that of genes involved in the innate immune system, which suggests a potential role for nasal tissue in initial viral infection, transmission and clearance.

Previous research had shown that nasal swabs from patients with symptomatic or asymptomatic COVID-19 respiratory disease (the disease caused by SARS-CoV-2) exhibit higher viral concentrations than those in throat swabs. This has implicated the nasal passage as a potential gateway for initial infection and transmission.

ACE2 and TMPRSS2 are two molecules involved in SARS-CoV-2 viral entry. To clarify the expression patterns of the genes encoding ACE2 and TMPRSS2, Waradon Sungnak and colleagues from the Lung Biological Network at the Wellcome Sanger Institute, Cambridge, examined various human tissue samples obtained from healthy donors. The authors analysed data for tissues from various parts of the respiratory system, the retina, skeletal muscle, prostate, brain and skin, among other locations. They confirmed the expression of ACE2 in multiple tissues implicated in prior research. They also detected ACE2 expression in tissues not previously analysed, along with its co-expression with TMPRSS2.

The authors found high expression of ACE2 and TMPRSS2 in nasal goblet and ciliated cells, which produce mucus. This suggests that these cells are the location of original viral infection and are possibly the source of dissemination within and between people.
The authors conclude that their results could potentially have implications for future treatment and prevention of COVID-19.

We investigated SARS-CoV-2 potential tropism by surveying expression of viral entry-associated genes in single-cell RNA-sequencing data from multiple tissues from healthy human donors. We co-detected these transcripts in specific respiratory, corneal and intestinal epithelial cells, potentially explaining the high efficiency of SARS-CoV-2 transmission. These genes are co-expressed in nasal epithelial cells with genes involved in innate immunity, highlighting the cells’ potential role in initial viral infection, spread and clearance. The study offers a useful resource for further lines of inquiry with valuable clinical samples from COVID-19 patients and we provide our data in a comprehensive, open and user-friendly fashion at

Waradon Sungnak, Ni Huang, Christophe Bécavin, Marijn Berg, Rachel Queen, Monika Litvinukova, Carlos Talavera-López, Henrike Maatz, Daniel Reichart, Fotios Sampaziotis, Kaylee B Worlock, Masahiro Yoshida, Josephine L Barnes the HCA Lung Biological Network

Nature Medicine abstract

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