A research team from the Berlin Institute for Health Research (BIH), together with researchers from the UK and Canada, has identified genes and proteins that lead to a higher risk of severe COVID-19. Their findings were recently published inNature Communications“superior.
Doctors and scientists around the world remain baffled as to why some people develop severe illness after contracting SARS-CoV-2, the virus that causes COVID-19 disease, while others experience only mild symptoms. A team of scientists at the BIH Center for Digital Health has identified a number of genes — in addition to known risk factors such as age and gender — that predispose people to experience more severe infections.
Maik Pietzner, lead author of the study, explained: “It was observed earlier that susceptibility to infection depends on a person’s blood type, for example, blood type is inherited. So it is clear that at least part of the disease process is determined by genetics.”
“BIH scientists have access to genetic data that researchers have collected from COVID-19 patients around the world, which also includes disease severity. At the time, approximately 17 genomic regions were observed to be associated with higher rates of severe COVID-19. risk,” explains Pietzner, “but the genes and underlying mechanisms that cause disease in many people remain unknown.”
Previously, BIH’s Computational Medicine Group has developed a “proteogenomics” approach to link protein-coding regions of DNA to disease through protein products. In the new study, they applied this approach to COVID-19 and discovered eight proteins of particular interest. “One of them is the protein responsible for an individual’s blood type,” explains Claudia Langenberg, head of the Computational Medicine Group.
“We knew this gene was associated with the risk of infection, so it was like a proof-of-concept. At the same time, it seemed like the protein ELF5 might make more sense. We found that COVID-19 patients who carried a variant of the gene encoding ELF5 were more likely to Hospitalization and ventilation, and in some cases death – so we did a careful study.”
The team turned to colleagues in the Intelligent Imaging Group led by Christian Conrad for their expertise in single-cell analysis. Lorenz Chua, a doctoral student in the group, was immediately keen to figure out which cells showed particular abundance of the ELF5 protein. “We found that ELF5 is present in all surface cells of the skin and mucous membranes, but is produced in particularly high amounts in the lungs. Since this is where the virus does most of its damage, this seems very plausible.”
But Conrad dismissed hopes that researchers might have identified new target molecules for drug development: “ELF5 is a so-called transcription factor that controls how often or how many other genes turn on and off throughout the body. Unfortunately, it’s hard to imagine Interfere with this protein in any way, as this will undoubtedly cause many undesired side effects.”
Among the eight proteins, however, the scientists found another intriguing candidate: the protein G-CSF, which acts as a growth factor for blood cells. They found that COVID-19 patients who genetically made more G-CSF had a milder disease course. Synthetic G-CSF has long been available as a drug, so it has the potential to be used as a treatment for COVID-19.
Translating this genetic discovery into clinical application is not an easy or quick process. This work – only possible with the support of many scientists and clinicians at BIH and Charité, and open results from studies around the world – underscores how open science and the efforts of international teams are making step-by-step discoveries of our genetic makeup How the tiniest change in disease can alter the course of a disease, in this case COVID-19.
“We started with global data on 100,000 participants and ended up looking at single molecules in individual cells. We believe collaborations that allow us to quickly move from the big picture and study large populations to in-depth molecular tracking can help us better Understanding the clinical consequences of this virus provides important lessons for future pandemics,” Pietzner concluded.