Complex Structure of Medical Genetics, R. Binaghi Hospital, Area Socio-Sanitaria Locale (ASSL) Cagliari, Azienda per la Tutela della Salute (ATS) Sardegna, Italy.
Associazione per l'Avanzamento della Ricerca per i Trapianti O.d.V., non profit organisation, Cagliari, Italy.
Front Immunol. 2020 Dec 4;11:605688. doi: 10.3389/fimmu.2020.605688. eCollection 2020.
SARS-CoV-2 infection is a world-wide public health problem. Several aspects of its pathogenesis and the related clinical consequences still need elucidation. In Italy, Sardinia has had very low numbers of infections. Taking advantage of the low genetic polymorphism in the Sardinian population, we analyzed clinical, genetic and immunogenetic factors, with particular attention to HLA class I and II molecules, to evaluate their influence on susceptibility to SARS-CoV-2 infection and the clinical outcome.
We recruited 619 healthy Sardinian controls and 182 SARS-CoV-2 patients. Thirty-nine patients required hospital care and 143 were without symptoms, pauci-symptomatic or with mild disease. For all participants, we collected demographic and clinical data and analyzed the HLA allele and haplotype frequencies.
Male sex and older age were more frequent in hospitalized patients, none of whom had been vaccinated during the previous seasonal flu vaccination campaignes. Compared to the group of asymptomatic or pauci-symptomatic patients, hospitalized patients also had a higher frequency of autoimmune diseases and glucose-6-phosphate-dehydrogenase (G6PDH) deficiency. None of these patients carried the beta-thalassemia trait, a relatively common finding in the Sardinian population. The extended haplotype HLA-A02:05, B58:01, C07:01, DRB103:01 [OR 0.1 (95% CI 0-0.6), Pc = 0.015] was absent in all 182 patients, while the HLA-C04:01 allele and the three-loci haplotype HLA-A30:02, B14:02, C08:02 [OR 3.8 (95% CI 1.8-8.1), Pc = 0.025] were more frequently represented in patients than controls. In a comparison between in-patients and home care patients, the HLA-DRB1*08:01 allele was exclusively present in the hospitalized patients [OR > 2.5 (95% CI 2.7-220.6), Pc = 0.024].
The data emerging from our study suggest that the extended haplotype HLA-A02:05, B58:01, C07:01, DRB103:01 has a protective effect against SARS-CoV-2 infection in the Sardinian population. Genetic factors that resulted to have a negative influence on the disease course were presence of the HLA-DRB1*08:01 allele and G6PDH deficiency, but not the beta-thalassemic trait. Absence of influenza vaccination could be a predisposing factor for more severe disease.
SARS-CoV-2 感染是一个全球性的公共卫生问题。其发病机制的几个方面及其相关的临床后果仍需要阐明。在意大利，撒丁岛的感染人数非常少。利用撒丁岛人群中较低的遗传多态性，我们分析了临床、遗传和免疫遗传学因素，特别关注 HLA Ⅰ类和Ⅱ类分子，以评估它们对 SARS-CoV-2 感染易感性和临床结果的影响。
我们招募了 619 名健康的撒丁岛对照者和 182 名 SARS-CoV-2 患者。39 名患者需要住院治疗，143 名患者无症状、症状轻微或轻度。对所有参与者，我们收集了人口统计学和临床数据，并分析了 HLA 等位基因和单倍型频率。
住院患者中男性和年龄较大的比例较高，他们在之前的季节性流感疫苗接种活动中均未接种疫苗。与无症状或症状轻微的患者相比，住院患者还具有更高的自身免疫性疾病和葡萄糖-6-磷酸脱氢酶（G6PDH）缺乏症的发生率。这些患者中没有β地中海贫血的特征，β地中海贫血在撒丁岛人群中较为常见。在所有 182 名患者中均未发现 HLA-A02:05、B58:01、C07:01、DRB103:01 的扩展单倍型[OR 0.1（95%CI 0-0.6），Pc = 0.015]，而 HLA-C04:01 等位基因和 HLA-A30:02、B14:02、C08:02 的三个位点单倍型[OR 3.8（95%CI 1.8-8.1），Pc = 0.025]在患者中比对照组更频繁出现。在住院患者与家庭护理患者之间的比较中，HLA-DRB1*08:01 等位基因仅存在于住院患者中[OR > 2.5（95%CI 2.7-220.6），Pc = 0.024]。
我们的研究结果表明，在撒丁岛人群中，扩展的 HLA-A02:05、B58:01、C07:01、DRB103:01 单倍型对 SARS-CoV-2 感染具有保护作用。对疾病进程有负面影响的遗传因素是 HLA-DRB1*08:01 等位基因和 G6PDH 缺乏，但不是β地中海贫血特征。未接种流感疫苗可能是疾病更严重的一个诱发因素。
