Researchers at HSE University became the first in the world to discover a genetic predisposition for serious COVID-19. The results of the study were published in the journal Limits in immunology.
T-cell immunity is one of the key mechanisms that the human body uses to fight viral infections. The basis for the development of cellular immunity is the presentation of viral peptides on the surface of infected cells. This is followed by activation of T lymphocytes, which begin to kill infected cells. The ability to successfully present viral peptides is largely determined by genetics.
In human cells, class I human leukocyte antigen (HLA-I) molecules are responsible for this presentation. The set of six such molecules is unique in each human and is inherited from the parents of the individual. Simply put, if a set of alleles detects the virus well, the immune cells will quickly detect and destroy the infected cells; if a person has a set that is bad at such detection, a more severe case of the disease is more likely to be noticed.
Researchers from the Faculty of Biology and Biotechnology of HSE – Maxim Shkurnikov, Stepan Nersisyan, Alexei Galatenko and Alexander Tonevitsky – together with colleagues from the Russian National Medical University Pirogov and Filatov City Clinical Hospital (Tatjana Jankevic, Ivan Gordeev, Valery Vechorko) studied the interrelationship HLA-I and COVID-19 weights.
Using machine learning, they built a model that provides a comprehensive assessment of the possible strength of the T-cell immune response to COVID-19: if a set of HLA-I alleles allows efficient presentation of SARS-CoV-2 virus peptides, those individuals received a low-risk score while individuals with lower presentation ability received higher risk scores (ranging from 0 to 100). To confirm the model, the genotypes of over 100 patients suffering from COVID-19 and over 400 healthy people were analyzed (control group). The modeled risk assessment turned out to be very effective in predicting the severity of COVID-19.
In addition to analyzing the Moscow population, the researchers used their model on a sample of patients from Madrid, Spain. High prediction accuracy was also confirmed in this independent sample: the risk score in patients suffering from severe COVID-19 was significantly higher than in patients with moderate and mild cases.
In addition to the revealed correlation between genotype and severity of COVID-19, the proposed approach also helps to assess how a particular mutation in COVID-19 may affect the development of T-cell immunity to the virus. For example, we will be able to identify groups of patients in whom infection with new strains of SARS-CoV-2 can lead to more severe forms of the disease. “
Alexander Tonevitsky, HSE Faculty of Biology and Biotechnology
National Research University Higher School of Economics