tetano
Editor, Senior Moderator
J Transl Med
. 2025 Mar 10;23(1):303.
doi: 10.1186/s12967-025-06285-w. A rapid ecologic analysis, confirmed by a case-control study, identifies class I HLA alleles correlated to the risk of COVID-19
Pierpaolo Correale[SUP] 1 [/SUP], Giovanni Baglio[SUP] 2 [/SUP], Roberto Parrella[SUP] 3 4 [/SUP], Rita Emilena Saladino[SUP] 5 [/SUP], Nunzia Cuomo[SUP] 6 [/SUP], Francesco Scarano[SUP] 3 [/SUP], Marina Francone[SUP] 5 [/SUP], Maria Cuzzola[SUP] 5 [/SUP], Giuseppe Foti[SUP] 7 [/SUP], Luciano Mutti[SUP] 8 9 [/SUP], Francesca Pentimalli[SUP] 10 [/SUP], Antonio Giordano[SUP] 11 12 [/SUP]
Affiliations
Background: 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-C*01 and -B*44 alleles in specific inter and intraregional populations along the first spreading wave.
Methods: 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.
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[SUB]adj[/SUB] = 3.193; p = 0.015); -B*14:01 (OR[SUB]adj[/SUB] = 3.596; p = 0.018); -B*15:01 (OR[SUB]adj[/SUB] = 5.124; p = 0.001); -B*35 (OR[SUB]adj[/SUB] = 2.972; p = 0.002).
Conclusions: 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.
Keywords: COVID-19; HLA; Italian bone marrow donor registry; SARS-CoV-2.
. 2025 Mar 10;23(1):303.
doi: 10.1186/s12967-025-06285-w. A rapid ecologic analysis, confirmed by a case-control study, identifies class I HLA alleles correlated to the risk of COVID-19
Pierpaolo Correale[SUP] 1 [/SUP], Giovanni Baglio[SUP] 2 [/SUP], Roberto Parrella[SUP] 3 4 [/SUP], Rita Emilena Saladino[SUP] 5 [/SUP], Nunzia Cuomo[SUP] 6 [/SUP], Francesco Scarano[SUP] 3 [/SUP], Marina Francone[SUP] 5 [/SUP], Maria Cuzzola[SUP] 5 [/SUP], Giuseppe Foti[SUP] 7 [/SUP], Luciano Mutti[SUP] 8 9 [/SUP], Francesca Pentimalli[SUP] 10 [/SUP], Antonio Giordano[SUP] 11 12 [/SUP]
Affiliations
- PMID: 40065352
- PMCID: PMC11892203
- DOI: 10.1186/s12967-025-06285-w
Background: 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-C*01 and -B*44 alleles in specific inter and intraregional populations along the first spreading wave.
Methods: 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.
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[SUB]adj[/SUB] = 3.193; p = 0.015); -B*14:01 (OR[SUB]adj[/SUB] = 3.596; p = 0.018); -B*15:01 (OR[SUB]adj[/SUB] = 5.124; p = 0.001); -B*35 (OR[SUB]adj[/SUB] = 2.972; p = 0.002).
Conclusions: 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.
Keywords: COVID-19; HLA; Italian bone marrow donor registry; SARS-CoV-2.