Although more research on the new coronavirus appears every day, doctors still do not understand why some infected people experience mild or no symptoms while others become critically ill. A new study, published in the New England Journal of Medicine, sheds more light on the genetic risk factors that make people more or less susceptible to severe COVID-19.

Researchers at the Beth Israel Deaconess Medical Center in Boston (USA) decided to investigate how genetic variation is associated with the severity of COVID-19. To do this, they used their own database of human proteins and metabolites, created over the last ten years.

“Patients with COVID-19 display a wide range of clinical manifestations and degrees of severity, ranging from flu-like symptoms to acute respiratory distress,” said study lead author Robert E. Gerszten.

“While pre-existing conditions, particularly cardiovascular and metabolic diseases, are risk factors, the underlying reasons why some people develop a life-threatening disease while others remain asymptomatic are not well understood.”

Two determining regions

The authors looked at the genomes of 4,856 patients from China, Europe and the United States who had had COVID-19 and found variations in two regions of the genome that determined the severity of the disease. They then identified which proteins these regions encode and what role these proteins played in the body in the context of disease.

One of the two regions of the genome was associated with the CD209 antigen, a protein through which the SARS-CoV-2 virus infects human cells.

“Scientists are finding more and more genome hot spots associated with COVID-19, but it is often unclear how they affect disease mechanisms,” Gershten said.

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Using their huge database of more than 100 terabytes, the scientists quickly determined that a protein that is most strongly expressed in that region is the coreceptor for the virus that causes COVID-19.

The second region of the genome identified by the researchers is associated with the CXCL16 protein, an inflammatory chemokine that scientists say plays a role in attracting immune cells (lymphocytes) to sites of infection.

The authors hope that this new knowledge will contribute to the development of new and better therapeutic interventions for patients with severe COVID-19.