ArticleJournal of translational medicine2025
A rapid ecologic analysis, confirmed by a case-control study, identifies class I HLA alleles correlated to the risk of COVID-19.
Article in Journal of translational medicine, 2025. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Not yet cited in PubMed.
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Abstract
backgroundSeveral 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-C*01 and -B*44 alleles in specific inter and intraregional populations along the first spreading wave.
methodsConsidering 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.
results| Our data revealed that the direct correlation of HLA-C*01, and HLA-B*44 gene expression and COVID-19 risk was completely lost just after the first pandemics wave in Italy. On the contrary, the expression of HLA-B*49 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-B*49 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-B*08 (OR
conclusionsOur 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.
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