More than 55 million people across the globe have contracted Covid-19, and 1.3 million have died as a result. Whilst most Covid-19 patients predominantly suffer from respiratory symptoms, the virus is not restricted to the respiratory tract, and can affect other organs as well. Often, the gastrointestinal tract is affected. A team led by Prof. Dr. Christoph Becker from Department of Medicine 1- Gastroenterology, Pneumology and Endocrinology at Universitätsklinikum Erlangen and a team from the Charité – Universitätsmedizin Berlin have discovered that there is a particularly high density of coronavirus docking sites in the gut epithelium. The researchers’ results were recently published in the renowned journal ‘Gastroenterology’.
During an infection with Sars-CoV-2, viruses dock on to the surface of host cells via certain structures on the surface, known as receptors. Once the virus shell attaches to the ACE2 receptor, the body’s own enzyme TMPRSS2 splits a viral protein, letting the virus enter the host cell. Once in the host cell, the virus can use it to create components required to produce more viruses. Once a sufficient number has been produced, the viruses can break out of the host cell and infect other cells themselves. The significance of ACE2 and TMPRSS2 for allowing Sars-CoV-2 to penetrate cells means that these two molecules offer a potential approach for effective medication against coronavirus.
Intestinal lining as target
The researchers from Erlangen and Berlin have now discovered that certain cells in the intestinal lining known as enterocytes have a high concentration of ACE2 and TMPRSS2 in healthy people and could therefore be susceptible to attack by coronavirus. Researchers also discovered that patients with intestinal inflammation have fewer ACE2 receptors, and that both ACE2 and TMPRSS2 change their localisation in the enterocytes. That may mean that the intestines of patients with chronic inflammatory bowel disease such as Morbus Crohn are more resistant towards Sars-CoV-2 than those of healthy people. ‘However, no major studies have yet been carried out on the impact of a coronavirus infection in the intestines,’ says Prof. Becker.
The research also indicated that the production of ACE2 and TMPRSS2 on the cell surface can be influenced by external factors. For example, stimulating the cells with certain microbial signals and messenger substances from the immune system leads to lower expression levels of ACE2 in the gut epithelium. ‘Our findings indicate that it may be possible to treat the infection by influencing the molecules on the cell surface required for an infection with Sars-CoV-2,’ explains Dr. Jay Patankar, one of the authors from Erlangen. As a next step, the team of researchers are planning to carry out infection experiments on cells to check their hypothesis.
The study was made possible thanks to a research network between Friedrich-Alexander-Universität Erlangen-Nürnberg and Charité – Universitätsmedizin Berlin. Both locations are leaders in the field of intestinal research within Germany. In a joint collaborative research centre, researchers from both cities are working together to investigate inflammatory bowel disease. At the heart of the collaborative research centre is the joint tissue bank IBDome, where intestinal samples from healthy people and patients with inflammatory bowel diseases are collected and analysed. ‘Thanks to the IBDome, we were able to access an extremely large number of biological samples in a very short space of time,’ explains Prof. Becker. The researchers now hope to find out exactly how Covid-19 affects the intestines and the functions of the cells present there.