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Researchers reveal a genetic predisposition to severe COVID-19

Credit: S. Nersisyan et al.

HSE researchers became the first to discover a genetic predisposition to severe COVID-19. The results of the study have been published in the journal Frontiers in Immunology.

T-cell immunity is one of the main mechanisms that the human body uses to fight viral infections. The starting point for the development of cell immunity is the exposure of virus peptides to the surface of infected cells. This is followed by activation of T lymphocytes, which begin to kill the infected cells.
The ability to successfully present peptides of a virus is largely determined by genetics. In human cells, class I (HLA-I) human leukocyte antigen (HLA-I) molecules are responsible for this presentation. The group of six molecules is unique to each human being and inherited from the parents of the individual. In simple terms, if the set of alleles detects the virus well, the immune cells will quickly detect and destroy the affected cells; If a person has a bad combination at this finding, a more severe disease state is likely to be observed.

Researchers from the HSE School of Biology and Biotechnology – Maxim Shkornikov, Stepan Nersisyan, Alexei Galatenko, and Alexander Tonievsky – together with colleagues from Russia’s Pirogov University of National Medical Research and Filatov City Clinical Hospital (Tatyana Yankevich, Ivan Gordiev and Valery Vychorko) have studied the HLA-pattern correlation The severity of COVID-19.

Using machine learning, they built a model that provides an integrated assessment of the potential strength of the T-cell immune response to COVID-19: If the HLA-I group of alleles allows for effective exposure of SARS-CoV-2 peptides, these individuals received a low risk score, while subjects received Those with the lowest exposure have higher risk scores (in the range 0 to 100). To validate the model, the genotypes of more than 100 patients who had suffered from COVID-19 and more than 400 healthy (control group) were analyzed. The typical risk score has turned out to be very effective in predicting the severity of COVID-19.

In addition to analyzing Muscovites, the researchers used their model on a sample of patients from Madrid, Spain. The high accuracy of the prediction was confirmed in this independent sample as well: the risk score for patients with severe COVID-19 was significantly higher than for patients with moderate and mild cases of disease.

In addition to the links discovered between genotype and COVID-19 severity, the proposed approach also helps assess how a specific mutation of COVID-19 might affect the development of T-cell immunity to the virus. For example, we will be able to uncover groups of patients in whom new strains of SARS-CoV-2 could lead to more severe forms of the disease, Alexander Tonievsky said.

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Once published, the paper will be available for viewing online at http: // doi.Deer /10.3389 /Vimeo.2021.641900 /. Limited through February 23, 2021, 00:00 EST / 06:00 (CET).

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