The experience of individuals with Coronavirus Disease 2019 (COVID-19) ranges from asymptomatic to life threatening multi-organ dysfunction. Specific HLA alleles may affect the predisposition to severe COVID-19 because of their role in presenting viral peptides to launch the adaptive immune response to severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). In this population-based case–control study in the midwestern United States, we performed high-resolution HLA typing of 234 cases hospitalized for COVID-19 in the St. Louis metropolitan area and compared their HLA allele frequencies with those of 22,000 matched controls from the National Marrow Donor Program (NMDP). We identified two predisposing alleles, HLA-DRB1*08:02 in the Hispanic group (OR = 9.0, 95% confidence interval: 2.2–37.9; adjusted p = 0.03) and HLA-A*30:02 in younger African Americans with ages below the median (OR = 2.2, 1.4–3.6; adjusted p = 0.01), and several candidate alleles with potential associations with COVID-19 in African American, White, and Hispanic groups. We also detected risk-associated amino acid residues in the peptide binding grooves of some of these alleles, suggesting the presence of functional associations. These findings support the notion that specific HLA alleles may be protective or predisposing factors to COVID-19. Future consortium analysis of pooled cases and controls is warranted to validate and extend these findings, and correlation with viral peptide binding studies will provide additional evidence for the functional association between HLA alleles and COVID-19.

中文翻译：

---

美国中西部 2019 年冠状病毒病患者的 HLA 基因多态性

2019 年冠状病毒病 (COVID-19) 患者的经历从无症状到危及生命的多器官功能障碍不等。特定的 HLA 等位基因可能会影响对严重 COVID-19 的易感性，因为它们在呈递病毒肽以启动对严重急性呼吸综合征冠状病毒 2 (SARS-CoV-2) 的适应性免疫反应中的作用。在美国中西部的这项基于人群的病例对照研究中，我们对圣路易斯大都会地区因 COVID-19 住院的 234 例病例进行了高分辨率 HLA 分型，并将其 HLA 等位基因频率与来自美国的 22,000 名匹配对照进行了比较国家骨髓捐赠计划 (NMDP)。我们在西班牙裔人群中鉴定了两个易感等位基因HLA-DRB1*08:02（OR = 9.0，95% 置信区间：2.2-37.9；调整后p = 0.03）和HLA-A*30:02在年龄低于中位数的年轻非裔美国人中（OR = 2.2, 1.4-3.6；调整后的p = 0.01），以及在非裔美国人中可能与 COVID-19 相关的几个候选等位基因、白人和西班牙裔群体。我们还在其中一些等位基因的肽结合槽中检测到与风险相关的氨基酸残基，表明存在功能关联。这些发现支持特定 HLA 等位基因可能是 COVID-19 的保护或易感因素的观点。有必要对合并的病例和对照进行未来的联合分析，以验证和扩展这些发现，并且与病毒肽结合研究的相关性将为 HLA 等位基因和 COVID-19 之间的功能关联提供额外的证据。