Genetics and complications from Sars-Cov-2: the blood type and a variation on chromosome 3 are risk factors

People who belong to blood group A and those who have a specific genetic variation on chromosome 3 are more at risk of developing a severe form of Covid-19. It is the result of a pilot study by GWAS (Genome-Wide Association Study), a European research led by the Universities of Kiel (Germany) and Oslo (Norway) with the participation of seven Italian and Spanish hospitals (Milan, Monza, Madrid , San Sebastian and Barcelona). Humanitas University-Humanitas Clinical Institute, together with Bicocca University-San Gerardo Hospital of Monza and Policlinico of Milan, contributed to the study, published in the New England Journal of Medicine.

Stefano Duga, professor at Humanitas University, is one of the authors of the study, with his colleague Rosanna Asselta. “Our goal – he explains – was to understand what are the genetic components that cause the most severe form of Sars-Cov-2 infection. We analyzed the samples of 1,980 patients with acute respiratory distress, comparing them with the individuals representing the controls. We evaluated millions of genetic variations. ”

How was the genetic research carried out?

The work has been extended to the whole genome, with a focus on the severity of Covid-19 disease. We examined patients who needed respiratory support, hospitalized in intensive care and intubated. We looked for regions of the genome in which the most seriously ill patients have frequencies of genetic variations that are significantly different compared to the control subjects. When you see these signs, it means that there is a gene in that region that can play a role in disease, which can be predisposing or protective.

What risk factors have you identified?

The first element we found is a signal on chromosome 9, where the genes that control blood group 0 are. We highlighted that belonging to group 0 has a protective role against the more serious forms of Covid-19 disease, while belonging to group A represents a risk factor.

What is the link between disease severity and blood type?

We still don’t know for sure, but we learned from other studies that group 0 individuals usually have a lower risk of developing thromboembolic disorders,. This is due to a link between the blood group and some coagulation factors. We also know that Covid-19 disease could have important thromboembolic consequences.

What other signal has been identified?

We found another signal on chromosome 3. It corresponds to a group of genes including SLC6A20, which interacts with the protein ACE2, the main surface receptor used by the virus to infect the cell. Also, there are other genes in this region that are good candidates.

What developments can we expect for Covid-19 patients?

There are at least two potential future consequences for patient care. On the one hand, there is the possibility of classifying according to the risk of contracting a severe form.This will be very important in case of a new resurgence of the virus. We already know that the main risk factors are male gender, old age and the presence of underlying conditions, but genetic information may allow us to understand who is more at risk and needs to be monitored carefully. Another effect is the possibility to identify molecular targets for drugs.

What is it about?

When a sudden pandemic like this occurs, the development of new medicine cannot only be based on the study of new molecules, because it would take too long. we can identify the molecular mechanisms of the pathogenesis of the disease, and thus find targets for which we already have available medicine. The best known example is the use of heparin to counteract the thromboembolism. Genetic information allows to significantly shorten the time for drug testing.