HLA-DQB1*05:03 is associated with an increased risk of COVID-19 progression in the Bulgarian population.

The SARS-CoV-2 outbreak represents a global health problem. The different infection rates are heavily influenced by host genetic factors, such as variability in the HLA region. The aim of our study was to investigate whether certain HLA alleles in the Bulgarian population contribute to COVID-19 progression and their role in anti-SARS-CoV-2 immunity. We evaluated 76 patients diagnosed with COVID-19 and classified them according to severity as mild, moderate, and severe. Data from a population cohort (n = 539), representative of the Bulgarian population, was used for comparisons. We found that the HLA-DQB1*05:03 (OR = 3.13, pc = 0.0008) allele was significantly associated with COVID-19 severity. Several other class I and class II alleles showed a promising association with a predisposition to disease severity or a protective role in its progression. This is the first study to assess the association between HLA and COVID-19 progression in the Bulgarian population. Despite some limitations, our results suggest that certain HLA alleles play a role in the severity of SARS-CoV-2 infection and it would be interesting to further trace their effect in the context of long COVID.