Two specific cell types in the nose have been identified as likely initial infection points for Covid-19, according to a study published last night.
Researchers from the Wellcome Sanger Institute, University Medical Centre Groningen in The Netherlands, University Cote d’Azur and CNRS, Nice, France, and their collaborators, found that goblet and ciliated cells in the nose have high levels of the entry proteins that the Covid-19 virus uses to get into our cells.
Writing in the latest edition of Nature Medicine, the researchers said they found that cells in the eye and some other organs also contain the viral-entry proteins, and were able to predict how a key entry protein is regulated with other immune system genes, which could provide potential targets for the development of treatments to reduce transmission.
The researchers, as part of the Human Cell Atlas Lung Biological Network, analysed consortium datasets of single cell RNA sequencing, from more than 20 different tissues of non-infected people to look for which individual cells expressed both of two key entry proteins that are used by the Covid-19 virus to infect our cells.
First author Dr Waradon Sungnak, from Wellcome Sanger Institute, said: “We found that the receptor protein – ACE2 – and the TMPRSS2 protease that can activate SARS-CoV-2 entry are expressed in cells in different organs, including the cells on the inner lining of the nose.
“We then revealed that mucus-producing goblet cells and ciliated cells in the nose had the highest levels of both these Covid-19 virus proteins, of all cells in the airways. This makes these cells the most likely initial infection route for the virus.”
Dr Martijn Nawijn, from the University Medical Centre Groningen. The Netherlands, said, it is the first time these particular cells in the nose had been associated with Covid-19.
“While there are many factors that contribute to virus transmissibility, our findings are consistent with the rapid infection rates of the virus seen so far,” he said. “The location of these cells on the surface of the inside of the nose make them highly accessible to the virus, and also may assist with transmission to other people.”
The two key entry proteins ACE2 and TMPRSS2 were also found in cells in the cornea of the eye and in the lining of the intestine, suggesting another possible route of infection via the eye and tear ducts, and also revealed a potential for faecal-oral transmission.
When cells are damaged or fighting an infection, various immune genes are activated. The study showed that ACE2 receptor production in the nose cells is probably switched on at the same time as these other immune genes.
Senior author Dr Sarah Teichmann, from the Wellcome Sanger Institute and co-chair of the HCA Organising Committee, said: “As we’re building the Human Cell Atlas, it is already being used to understand Covid-19 and identify which of our cells are critical for initial infection and transmission. This information can be used to better understand how coronavirus spreads. Knowing which exact cell types are important for virus transmission also provides a basis for developing potential treatments to reduce the spread of the virus.”
* The World Health Organisation warned of a potential surge of cases in eastern Europe, where reported numbers of cases and deaths have been low. These include Russia and Turkey.
Regional director Dr Hans Kluge said: "Make no mistake, we remain in very turbulent water and will do so for some time.
He said: "There is no fast track to the new normal. The question is not whether there will be a second wave. The question is whether we will take into account the biggest lesson so far, namely to work between waves to strengthen readiness and surge for worst case scenarios."
Sungnak W, Huang N, Bécavin C et al. SARS-CoV-2 entry factors are highly expressed in nasal epithelial cells together with innate immune genes. Nature Medicine 23 April 2020; doi : 10.1038/s41591-020-0868-6
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