Human leukocyte antigen (HLA) genes with extreme diversity can make a contribution for individual variations to the immune response against SARS-COV-2 infection. This study aimed to explore the distributions of HLA class II alleles frequencies and their relations with disease severity in a group of Iranian COVID-19 patients. This prospective and case-control study was conducted on 144 COVID-19 patients including 46 cases with moderate form, 54 cases with severe and 44 cases with critical disease. HLA-DRB1 and -DQB1 allele families were determined by PCR-SSP method and compared between three groups of the patients and in comparison to 153 ethnic-matched healthy controls. The patients group showed lower frequencies of HLA-DRB1*15 (OR = 0.57, P = 0.06), DRB1*15 ~ DQB1*05 haplotype (P = 0.04) and DRB1*15/DRB1*04 genotype (P = 0.04) in compare with healthy controls. Moderate COVID-19 patients had higher frequencies of HLA-DRB1*04 (P = 0.03), HLA-DRB1*10 (P = 0.05) and DRB1*04/DRB1*11 genotype (P = 0.01). Also, a higher significantly frequency of HLA-DRB1*03 allele group was observed in the critical patients versus controls (P = 0.01). Multiple logistic regression analysis revealed that the presence of DRB1*04 allele group was negatively associated with development of severe and critical disease (OR: 0.289, P = 0.005). Our results indicate a possible contribution of some HLA class II alleles in disease severity and clinical features of COVID-19 disease.

具有极端多样性的人类白细胞抗原（HLA）基因可以为针对 SARS-COV-2 感染的免疫反应的个体差异做出贡献。本研究旨在探讨一组伊朗 COVID-19 患者的 HLA II 类等位基因频率分布及其与疾病严重程度的关系。这项前瞻性病例对照研究对 144 名 COVID-19 患者进行，其中中度病例 46 例，重症病例 54 例，危重病例 44 例。通过 PCR-SSP 方法确定HLA-DRB1和-DQB1等位基因家族，并在三组患者之间进行比较，并与 153 名种族匹配的健康对照进行比较。患者组中HLA-DRB1*15 (OR = 0.57, P = 0.06)、 DRB1*15 ~ DQB1*05单倍型 (P = 0.04) 和DRB1*15/DRB1*04基因型 (P = 0.04) 的频率较低。与健康对照进行比较。中度COVID-19患者的HLA-DRB1*04 （P=0.03）、 HLA-DRB1*10 （P=0.05）和DRB1*04/DRB1*11基因型频率较高（P=0.01）。此外，与对照组相比，危重患者中HLA-DRB1*03等位基因组的频率显着更高（P = 0.01）。多元Logistic回归分析显示， DRB1*04等位基因组的存在与重症、危重症的发生呈负相关（OR：0.289，P=0.005） 。我们的结果表明一些 HLA II 类等位基因可能对 COVID-19 疾病的疾病严重程度和临床特征做出贡献。