Researchers Identify New Possible Entry Points for SARS-CoV-2 into Human Bodies

A study has identified the intestine, kidneys, testes and placenta as potential hotspots of coronavirus infection in the human body.

Researchers from the German Center for Neurodegenerative Diseases (DZNE Tübingen, Germany) and Cornell University (Ithaca, NY, USA) have investigated cellular factors that could be significant for an infection. They analyzed the activity of 28 specific genes in a wide range of human tissues, leading to the creation of a map of potentially disease-relevant factors across the human body.

The researchers first began their study by identifying 28 human genes, respectively cellular factors, that enable the virus to enter human cells or that might otherwise be important for an infection. In addition to receptors on the cell surface, these included, for example, proteins that the pathogen presumably needs in order to multiply within a cell. Importantly, the list of studied factors also contained enzymes that block the penetration of pathogens into cells - known as “restrictors factors”. In summary, the 28 analyzed cellular features are dubbed “SCARFs” for “SARS-CoV-2 and coronavirus associated receptors and factors”.

Using information from scientific databases, the researchers analyzed gene activity - also known as “expression patterns” - in around 400,000 human cells from various types of tissue. These included nasal mucosa, lungs, gut, kidneys, heart, brain and reproductive organs. Analysis was done on a single-cell level and using sophisticated bioinformatics methods. In line with the known fact that SARS-CoV-2 attacks in particular the respiratory tract, the expression patterns identify the nasal mucosa as a “battleground”. Accordingly, cells of the nasal mucosa contain both factors that facilitate infection like the ACE2 receptor as well as factors that inhibit viral entry, like IFITM3 and LY6E. According to the current study, the intestine, kidneys, testes and placenta are potential hotspots, that is, these areas seem to be characterized by significant co-expression of ACE2 with TMPRSS2, an enzyme involved in viral entry in combination with ACE2.

“We were also able to identify a number of cellular factors that, as alternatives to the ACE2 receptor, could contribute to SARS-CoV-2 entering the lungs, heart and central nervous system,” said Dr. Vikas Bansal, a data scientist at the DZNE’s Tübingen site. “SARS-CoV-2 is by now known to be able to trigger neurological disorders. Although the virus has not yet been detected in neurons, the nervous system includes other cells such as astrocytes and pericytes that are for example involved in the regulation of the blood–brain barrier, which is the interface between the brain and the bloodstream. According to our study these cells might well be susceptible to infection. This could possibly involve a receptor called BSG. All in all, our study therefore provides a wealth of data and specific clues for future studies on the coronavirus.”

Related Links:
German Center for Neurodegenerative Diseases (DZNE)
Cornell University