Scientists have examined samples from non-virus infected patients to determine which cells of the lungs and bronchi are targets for novel coronavirus (SARS-CoV-2) infection. They discovered that the receptor for this coronavirus is abundantly expressed in certain progenitor cells. These cells normally develop into respiratory tract cells lined with hair-like projections called cilia that sweep mucus and bacteria out of the lungs. The scientists have now published their findings in The EMBO Journal.

The researchers initially intended to study why lung cancer sometimes occurs in people who have never smoked. They began by analyzing samples of twelve lung cancer patients. These samples were obtained from the Heidelberg Lung Biobank and came from both the cancerous part of the lungs and the surrounding healthy lung tissue. They also studied cells from the airways of healthy patients, which had been collected in a minimally invasive manner during a bronchoscopy examination performed to rule out lung cancer. The rapidly spreading coronavirus prompted the researchers to take another look at these existing but so far unpublished data. "I was convinced that the data we gathered from these non-coronavirus infected patients would provide important information for understanding the viral infection," says the senior author.

"We wanted to find out which specific cells the coronavirus attacks," explains another author. The scientists knew that the virus's spike protein attaches to an ACE2 receptor on the cell surface. In addition, the virus needs one or more cofactors for it to be able to penetrate cells. But which cells are endowed with such receptors and cofactors? Which cells in which part of the respiratory system are particularly susceptible to SARS-CoV-2 infection. The researchers now used single-cell sequencing technology to examine the cells in the samples from Heidelberg.

"We then analyzed a total of nearly 60,000 cells to determine whether they activated the gene for the receptor and potential cofactors, thus in principle allowing them to be infected by the coronavirus," reports one of the lead authors of the study now being published in The EMBO Journal. "We only found the gene transcripts for ACE2 and for the cofactor TMPRSS2 in very few cells, and only in very small numbers." They discovered that certain progenitor cells in the bronchi are mainly responsible for producing the coronavirus receptors. These progenitor cells normally develop into respiratory tract cells lined with hair-like projections called cilia that sweep mucus and bacteria out of the lungs. "Armed with the knowledge of which cells are attacked, we can now develop targeted therapies," explains another author.

An interesting additional finding of the study was that the ACE2 receptor density on the cells increased with age and was generally higher in men than in women. "This was only a trend, but it could explain why SARS-CoV-2 has infected more men than women," the senior author says. However, the author points out, "our sample sizes are still much too small to make conclusive statements, so we need to repeat the study in larger patient cohorts."

"These results show us that the virus acts in a highly selective manner, and that it is dependent on certain human cells in order to spread and replicate," the senior author explains. "The better we understand the interaction between the virus and its host, the better we will be able to develop effective counterstrategies." The researchers will next study COVID 19 patients to ascertain whether the virus has actually infected these cells. "We want to understand why the infection takes a benign course in some patients, while causing severe disease in others," the senior author says. "So we will also look closely at the immune cells in the infected tissue."

https://www.bihealth.org/en/notices/what-cells-does-the-novel-coronavirus-attack/

https://www.embopress.org/doi/10.15252/embj.20105114

http://sciencemission.com/site/index.php?page=news&type=view&id=publications%2Fsars-cov-2-receptor&filter=22