HLA-A, -B, -DRB1 genes polymorphism of in COVID-19 patients

• Ekaterina M. Rodnikova
• Kristina R. Dudina
• Tatyana E. Yankevich
• Vladislava V. Kadochnikova
• Margarita N. Boldyreva
• Dmitry Yu. Trofimov

Abstract

Introduction. The COVID-19 pandemic, which began at the end of 2019 in Wuhan, China, has unfolded differently in different countries. These differences cannot always be explained by different healthcare organizations. Clinical variations, severity of infection, favorable or fatal outcome of COVID-19 may also be associated with immunogenetic differences in hosts. Classical HLA proteins, the main function of which is to present peptides of infectious pathogens on the surface of Ag-presenting cells to T cells, which initiates an adaptive immune response. Different HLA alleles present different peptide repertoires, which can potentially influence the immune response. It has been shown that different alleles of HLA genes have been involved in host susceptibility or resistance to diseases such as tuberculosis, malaria, hepatitis B, dengue, influenza, and MERS.

Aim – to search for markers of sensitivity and severity of COVID-19 disease among alleles of the HLA-A, HLA-B, HLA-DRB1 genes in different age groups of patients.

Material and methods. All subjects included in the study are residents of Moscow. Population control – 98 people. Patients with COVID-19 were in the Infectious Clinical Hospital No. 1 of the Moscow in 2020–2021. The presence of the SARS-CoV-2 was confirmed by PCR. Patients with mild/moderate infection and a favorable outcome 65 years and younger (n = 316): m/f = 160/156, age Me = 48 years (18–65 years), over 65 years (n = 102): m/f = 43/59, age Me = 72 years (66–96 years), patients with severe disease and a favorable outcome, 65 years and younger (n = 75): m/f = 43/32, age Me = 52 years (32–60 years), over 65 years (n = 139): m/f = 49/90, age Me = 72 years (66–90 years); patients with severe infection and death 65 years and younger (n = 23): m/f = 12/113, age Me = 54 years (29–60 years), over 65 years (n = 88): m/f = 23/65, age Me = 74 years (66–94 years). Alleles of genes HLA-A, HLA-B, HLA-DRB1 were determined by NGS.

Results. After the number of studied alleles correction, the studied age groups of patients (over 65 years old and younger than 65 years) did not differ from the population control in the frequency profile of HLA genes. Markers of severe disease, but with a favorable outcome in the age group 65 years and younger were B*08:01 and DRB1*11:03. A marker of a milder course of the disease in the over 65 years old group was HLA B*5701. The marker of lethal outcome of severe COVID-19 infection in the over 65 years old group was HLA B*15:01.

Conclusion. The studied HLA genes are more likely associated with the severity and outcome of infection than with the fact of infection itself.

Keywords:COVID-19 patients; age; alleles HLA-A, HLA-B, HLA-DRB1; NGS method

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