HLA Polymorphisms and COVID-19 Susceptibility and Severity: Insights From an Iranian Patients Cohort 2025 Teimoori-Toolabi et al

ABSTRACT

The HLA system is a crucial immune response component against infectious agents, including SARS-CoV-2. Certain polymorphisms may impart varying levels of protection or vulnerability to COVID-19. This research aims to understand the possible relationship between HLA polymorphisms and the susceptibility to COVID-19 and its severity.

We recruited 290 hospitalised Iranian COVID-19 patients (130 severe and 160 moderate). Using PCR-SSP methods, we conducted a detailed analysis of polymorphisms in HLA class I (HLA-A, HLA-B, and HLA-C) and II (HLA-DRB1 and HLA-DQB1) molecules at low resolution.

The study found that certain HLA alleles, including HLA-B*49, HLA-B*52, HLA-C*12, HLA-DRB1*04, and HLA-DQB1*05, were associated with disease susceptibility. Additionally, HLA-A*23, DRB1*10, and DRB1*13 were indicators of disease severity.

The study also noted that individuals carrying the HLA-A*23 allele showed a significant decrease in lymphocyte levels and an elevated likelihood of developing thrombosis.

We hypothesise that a maladaptive immune response may occur based on these findings. This might be due to the strong affinity of the HLA-A*23 allele group for presenting a wide range of SARS-CoV-2 peptides. Such a presentation possibly leads to a cytokine storm, followed by lymphocyte apoptosis and an increase in platelet count.

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