Polymorphisms in HLA genes among Brazilian patients hospitalized with COVID-19: Insights from a multicentric study

Immunogenetic factors such as human leukocyte antigen (HLA) alleles, have yielded contrasting associations with protection or increased chances of hospitalization due to COVID-19 worldwide. This case-control study included 834 patients with confirmed COVID-19 diagnosis from five Brazilian states: Ceará (n = 110), Mato Grosso (n = 192), Pará (n = 209), Rio de Janeiro (n = 211) and Rio Grande do Sul (n = 112). Genotyping was performed using the Axiom™ Human Genotyping SARS-CoV-2 array, targeting single nucleotide polymorphisms in HLA class I and II genes; HLA alleles were imputed for eight loci. Among the 15 preselected candidate alleles, only DQA1∗05:01 (p = 0.015) in the state of Ceará remained significantly associated with hospitalization. The meta-analysis of the most frequent alleles in all states revealed that HLA-DPA1∗01:03 (p = 0.0229, OR = 0.76, 95 % CI = 0.60-0.96) and HLA-DPB1∗04:01 (p = 0.0474, OR = 0.78, 95 % CI = 0.611.00) were associated with protection against hospitalization, whereas HLA-DPA1∗02:01 (p = 0.0259, OR = 1.37, 95 % CI = 1.04-1.80), HLA-DQA1∗05:01 (p = 0.0133, OR = 1.40, 95 % CI = 1.07-1.82), and HLA-DRB1∗03:01 (p = 0.0276, OR: 1.59, 95 % CI: 1.05-2.40) associated with increased risk of hospitalization. HLA evolutionary divergence (HED) scores were significantly higher among the non-hospitalized group for the HLA-A locus, which has been shown to be a protective factor for the most severe forms and consequently hospitalization due to COVID-19.