March 7, 2021

Russian researchers find a genetic predisposing factor to severe COVID-19


T-cell immunity is one of the mechanisms used by the human body to fight viral infections. In fact, the starting point for the development of cellular immunity is the presentation of virus peptides on the surface of infected cells. This is when the activation of the T lymphocytes occurs, which begin to eliminate the ‘diseased’ cells.

Researchers from the National Research University from Russia have detailed how the ability to give this type of immune response to SARS-CoV-2 is largely determined by genetics. In human cells, those responsible are the human leukocyte antigen class I (HLA-I) molecules. The set of six of these molecules is unique in each human being and is inherited from the parents.

“The HLA-I genotype is an important factor for the immune response to any type of viral infection. In our work we show that individuals with specific HLA genotypes are more predisposed to having severe COVID-19. Similarly, there are some genotypes ‘strong’ that are rarely associated with a serious course of the disease “, explains to SINC Stepan Nersisyan, one of the authors of the work, published in Frontiers in Immunology.

Using machine learning, the team built a model that provides a comprehensive assessment of the potential potency of the immune response of T cells to COVID-19: whether the allele set [versiones del gen] HLA-I allows efficient presentation of SARS-CoV-2 virus peptides, those individuals received a low risk score, while those with less presentation ability received higher risk scores.

To validate the model, the genotypes of more than 100 patients who had suffered COVID-19 and of more than 400 healthy people were analyzed as a control group. The experts found that the simulated risk score is “very effective in predicting the severity of the disease.”

In addition to analyzing the Moscow population, the researchers used their model in a sample of patients from the Ramón y Cajal Hospital in Madrid (Spain). “The high precision of the prediction was also confirmed in this independent sample: the risk score of patients with severe COVID-19 was significantly higher than in patients with moderate and mild cases of the disease,” they point out.

Other applications of this model

In addition to the correlations discovered between the genotype and the severity of this disease, this new approach can help the evaluation of how a certain COVID-19 mutation would affect the development of T-cell immunity against the virus, say the researchers .

“For example, we will be able to detect groups of patients in whom infection with new strains of SARS-CoV-2 can lead to more severe forms of the disease,” stresses Alexander Tonevitsky, another of the authors.

For his part, Stepan Nersisyan adds that, in the context of a possible vaccine shortage, “knowledge of people with the HLA genotype at risk could prioritize this group for vaccination.” “Finally, knowing your own risk group can motivate people to maintain a more responsible social distance, to wear a mask and to do other things to be safer,” concludes Nersisyan.

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