Correale Pierpaolo, Baglio Giovanni, Parrella Roberto, Saladino Rita Emilena, Cuomo Nunzia, Scarano Francesco, Francone Marina, Cuzzola Maria, Foti Giuseppe, Mutti Luciano, Pentimalli Francesca, Giordano Antonio
Unit of Medical Oncology, Grand Metropolitan Hospital 'Bianchi Melacrino Morelli', I-89124, Reggio Calabria, Italy.
Research Unit of AGENAS, Italian National Agency for Regional Healthcare Services, Rome, Italy.
J Transl Med. 2025 Mar 10;23(1):303. doi: 10.1186/s12967-025-06285-w.
Several studies suggest that the heterogeneous spread of SARS-CoV-2 pandemics started on December 2019 could be partially upheld by the prevalence of permissive class I HLA alleles in specific populations. Such HLA alleles are in fact unable to shape an efficient anti-viral immune-response in the hosts or sustain an exaggerated inflammatory T cell mediated response responsible for the COVID-19 disease. We previously reported an ecologic correlation between the risk of COVID-19 spreading across Italy and the germinal expression of permissive HLA-C01 and -B44 alleles in specific inter and intraregional populations along the first spreading wave.
Considering that SARS-CoV-2 has undergone multiple adaptative mutations since the beginning of pandemics related to a natural immunization and to the worldwide campaign of anti-SARS-CoV-2 vaccination, we have carried out further analyses to evaluate whether the predictive value of class I HLA-allele gene prevalence and COVID-19 incidence has changed with time along the first four pandemics spreading waves in Italy. To this purpose we carried out an ecologic study followed by a case-control study.
| Our data revealed that the direct correlation of HLA-C01, and HLA-B44 gene expression and COVID-19 risk was completely lost just after the first pandemics wave in Italy. On the contrary, the expression of HLA-B49 allele in specific populations emerged as inversely correlated to the risk of COVID-19 and could be considered as a protective factor. The statistical significance of this correlation was progressively enforced in each subsequent spreading wave until February 2022. The following case-control study in the two Regions of Campania and Calabria in Italy confirmed the protective value of HLA-B49 allele gene expression (OR = 0.289; p = 0.041), although statistical significance is lost after adjustment by logistic regression model. The analysis also detected multiple class I HLA-alleles whose expression was strongly correlated with COVID-19 risk: HLA-B08 (OR = 3.193; p = 0.015); -B14:01 (OR = 3.596; p = 0.018); -B15:01 (OR = 5.124; p = 0.001); -B35 (OR = 2.972; p = 0.002).
Our study not only identifies specific HLA alleles related to COVID-19 risk but also exemplifies a rapid and inexpensive approach that can be used to identify individuals needing prioritization during vaccination campaigns.
多项研究表明，2019年12月开始的新冠病毒大流行的异质性传播，可能部分归因于特定人群中允许性I类HLA等位基因的流行。事实上，此类HLA等位基因无法在宿主中形成有效的抗病毒免疫反应，也无法维持导致新冠疾病的过度炎症性T细胞介导的反应。我们之前报告过，在意大利第一波疫情传播期间，新冠病毒在意大利传播的风险与特定区域间和区域内人群中允许性HLA-C01和 -B44等位基因的胚系表达之间存在生态学关联。
鉴于自新冠大流行开始以来，新冠病毒因自然免疫和全球范围内的抗新冠病毒疫苗接种运动而发生了多次适应性突变，我们进一步开展了分析，以评估在意大利的前四波疫情传播中，I类HLA等位基因基因流行率与新冠发病率之间的预测价值是否随时间发生了变化。为此，我们先进行了一项生态学研究，随后开展了一项病例对照研究。
我们的数据显示，在意大利第一波疫情之后，HLA-C01和HLA-B44基因表达与新冠风险之间的直接关联完全消失。相反，特定人群中HLA-B49等位基因的表达与新冠风险呈负相关，可被视为一个保护因素。在2022年2月之前的每一波后续传播中，这种关联的统计学显著性逐渐增强。在意大利坎帕尼亚和卡拉布里亚两个地区进行的后续病例对照研究证实了HLA-B49等位基因表达的保护价值（OR = 0.289；p = 0.041），尽管在通过逻辑回归模型进行调整后，统计学显著性消失。该分析还检测到多个I类HLA等位基因，其表达与新冠风险密切相关：HLA-B08（OR = 3.193；p = 0.015）；-B14:01（OR = 3.596；p = 0.018）；-B15:01（OR = 5.124；p = 0.001）；-B35（OR = 2.972；p = 0.002）。
我们的研究不仅确定了与新冠风险相关联的确切HLA等位基因类型，还例证了一种快速且经济的方法，可用于在疫苗接种运动中识别需要优先接种的个体。
