Effect of HLA Class II polymorphism on susceptibility to SARS-CoV-2 infection and severity of the infection process

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Abstract
Previous studies have revealed a potential role of gene variants in the main histocompatibility complex, which regulates the expression of human leukocyte antigen molecules ( HLA ) in the course of coronavirus infection (COVID-19). The aim of our study was to evaluate the relationships between HLA polymorphism and COVID-19, as well as the severity of the infection process in patients from the Western Siberia. 260 patients with COVID-19 were examined two months after their convalescence. The comparison group included 372 residents from the Novosibirsk Region. Genotyping of the alleles and allele groups was performed using PCR test-systems (DNA-Technology, Moscow, Russia). The IBM SPSS Statistics 23 and Harlequine 3.5.2 were used for statistical processing. An increase in DRB1*15; DQA1*01:02 alleles and decreased frequency of DRB1*03; DQA1*01:03; DQB1*05:03 were detected in COVID-19 patients versus control group. After Bonferroni correction, the mentioned differences retained only for DQA1*01:02 . Three haplotypes were identified, which differed between the groups without Bonferroni correction. DRB1*07,15; DQA1*01:02,0201 and DQB1*02,06:02-08 frequency prevailed in patients versus control group. DRB1*07,15-DQB1*02,06:02-08; DQA1*01:02,02:01-DQB1*02,06-02-08 , and DRB1*07,15DQA1*01:02,02:01-DQB1*02,06:02-08 combinations prevailed in COVID-19 patients against control group. The DRB1*07,11; DRB1*11,15 genotypes, and several allelic combinations ( DRB1*07,11-DQA1*02:01,05:01; DRB1*11,15-DQA1*01:02,05:01; DRB1*11,15-DQB1*03:01,06:02-08, DRB1*11,15-DQA1*01:02,05:01DQB1*03:01,06:02-08 ) were present only in patients with severe disease. Prevalence of DRB1*11, DRB1*07,11 and DRB1*07,11-DQA1*02:01,05:01 was higher in the combined group (severe plus moderate course) of the disease versus the group of patients with mild disease. The results obtained make a definite contribution to clarifying the role of HLA gene polymorphism in COVID-19 not only in Western Siberia, but also in the entire Russian Federation. Further research is required, with increasing the sample size, thus reaching statistical significance, when correcting for the multiplicity of alleles.

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