Human Leukocyte Antigen Complex and Other Immunogenetic and Clinical Factors Influence Susceptibility or Protection to SARS-CoV-2 Infection and Severity of the Disease Course. The Sardinian Experience
AimSARS-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...
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Frontiers Media S.A.
2020-12-01
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| Series: | Frontiers in Immunology |
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| Online Access: | https://www.frontiersin.org/articles/10.3389/fimmu.2020.605688/full |
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| author | Roberto Littera Roberto Littera Marcello Campagna Silvia Deidda Goffredo Angioni Selene Cipri Selene Cipri Maurizio Melis Davide Firinu Simonetta Santus Alberto Lai Rita Porcella Sara Lai Stefania Rassu Rosetta Scioscia Federico Meloni Daniele Schirru William Cordeddu Marta Anna Kowalik Maria Serra Paola Ragatzu Mauro Giovanni Carta Stefano Del Giacco Angelo Restivo Simona Deidda Sandro Orrù Antonella Palimodde Roberto Perra Germano Orrù Maria Conti Cinzia Balestrieri Giancarlo Serra Simona Onali Francesco Marongiu Andrea Perra Andrea Perra Luchino Chessa Luchino Chessa Luchino Chessa |
| author_facet | Roberto Littera Roberto Littera Marcello Campagna Silvia Deidda Goffredo Angioni Selene Cipri Selene Cipri Maurizio Melis Davide Firinu Simonetta Santus Alberto Lai Rita Porcella Sara Lai Stefania Rassu Rosetta Scioscia Federico Meloni Daniele Schirru William Cordeddu Marta Anna Kowalik Maria Serra Paola Ragatzu Mauro Giovanni Carta Stefano Del Giacco Angelo Restivo Simona Deidda Sandro Orrù Antonella Palimodde Roberto Perra Germano Orrù Maria Conti Cinzia Balestrieri Giancarlo Serra Simona Onali Francesco Marongiu Andrea Perra Andrea Perra Luchino Chessa Luchino Chessa Luchino Chessa |
| author_sort | Roberto Littera |
| collection | DOAJ |
| description | AimSARS-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.Method and MaterialsWe 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.ResultsMale 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-A*02:05, B*58:01, C*07:01, DRB1*03:01 [OR 0.1 (95% CI 0–0.6), Pc = 0.015] was absent in all 182 patients, while the HLA-C*04:01 allele and the three-loci haplotype HLA-A*30:02, B*14:02, C*08:02 [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].ConclusionThe data emerging from our study suggest that the extended haplotype HLA-A*02:05, B*58:01, C*07:01, DRB1*03:01 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. |
| first_indexed | 2024-12-24T09:59:17Z |
| format | Article |
| id | doaj.art-e25d3765122e4c519d53c63ec69cf502 |
| institution | Directory Open Access Journal |
| issn | 1664-3224 |
| language | English |
| last_indexed | 2024-12-24T09:59:17Z |
| publishDate | 2020-12-01 |
| publisher | Frontiers Media S.A. |
| record_format | Article |
| series | Frontiers in Immunology |
| spelling | doaj.art-e25d3765122e4c519d53c63ec69cf5022022-12-21T17:01:11ZengFrontiers Media S.A.Frontiers in Immunology1664-32242020-12-011110.3389/fimmu.2020.605688605688Human Leukocyte Antigen Complex and Other Immunogenetic and Clinical Factors Influence Susceptibility or Protection to SARS-CoV-2 Infection and Severity of the Disease Course. The Sardinian ExperienceRoberto Littera0Roberto Littera1Marcello Campagna2Silvia Deidda3Goffredo Angioni4Selene Cipri5Selene Cipri6Maurizio Melis7Davide Firinu8Simonetta Santus9Alberto Lai10Rita Porcella11Sara Lai12Stefania Rassu13Rosetta Scioscia14Federico Meloni15Daniele Schirru16William Cordeddu17Marta Anna Kowalik18Maria Serra19Paola Ragatzu20Mauro Giovanni Carta21Stefano Del Giacco22Angelo Restivo23Simona Deidda24Sandro Orrù25Antonella Palimodde26Roberto Perra27Germano Orrù28Maria Conti29Cinzia Balestrieri30Giancarlo Serra31Simona Onali32Francesco Marongiu33Andrea Perra34Andrea Perra35Luchino Chessa36Luchino Chessa37Luchino Chessa38Complex Structure of Medical Genetics, R. Binaghi Hospital, Area Socio-Sanitaria Locale (ASSL) Cagliari, Azienda per la Tutela della Salute (ATS) Sardegna, ItalyAssociazione per l’Avanzamento della Ricerca per i Trapianti O.d.V., non profit organisation, Cagliari, ItalyDepartment of Medical Sciences and Public Health, University of Cagliari, Cagliari, ItalyComplex Structure of Pneumology, PO SS Trinità, ASSL Cagliari, ATS Sardegna, Cagliari, ItalyComplex Structure of Infectious Diseases, PO SS Trinità, ASSL Cagliari ATS Sardegna, Cagliari, ItalyComplex Structure of Medical Genetics, R. Binaghi Hospital, Area Socio-Sanitaria Locale (ASSL) Cagliari, Azienda per la Tutela della Salute (ATS) Sardegna, ItalyDepartment of Medical Biotechnology and Translational Medicine, University of Milan, Milan, ItalyDepartment of Medical Sciences and Public Health, University of Cagliari, Cagliari, ItalyDepartment of Medical Sciences and Public Health, University of Cagliari, Cagliari, ItalyUnitá di Crisi Locale (UCL) ATS Sardegna, Cagliari, ItalyUnitá di Crisi Locale (UCL) ATS Sardegna, Cagliari, ItalyComplex Structure of Medical Genetics, R. Binaghi Hospital, Area Socio-Sanitaria Locale (ASSL) Cagliari, Azienda per la Tutela della Salute (ATS) Sardegna, ItalyComplex Structure of Medical Genetics, R. Binaghi Hospital, Area Socio-Sanitaria Locale (ASSL) Cagliari, Azienda per la Tutela della Salute (ATS) Sardegna, ItalyComplex Structure of Medical Genetics, R. Binaghi Hospital, Area Socio-Sanitaria Locale (ASSL) Cagliari, Azienda per la Tutela della Salute (ATS) Sardegna, ItalyDepartment of Medical Sciences and Public Health, University of Cagliari, Cagliari, ItalyDepartment of Medical Sciences and Public Health, University of Cagliari, Cagliari, ItalyDepartment of Medical Sciences and Public Health, University of Cagliari, Cagliari, ItalyComplex Structure of Infectious Diseases, PO SS Trinità, ASSL Cagliari ATS Sardegna, Cagliari, ItalyUnit of Oncology and Molecular Pathology, Department of Biomedical Sciences, University of Cagliari, Cagliari, ItalyMedical Genetics, Department of Medical Sciences and Public Health, University of Cagliari, Cagliari, ItalyMedical Genetics, Department of Medical Sciences and Public Health, University of Cagliari, Cagliari, ItalyDepartment of Medical Sciences and Public Health, University of Cagliari, Cagliari, ItalyDepartment of Medical Sciences and Public Health, University of Cagliari, Cagliari, Italy0Colorectal Surgery Unit, Department of Surgical Science, University of Cagliari, Cagliari, Italy0Colorectal Surgery Unit, Department of Surgical Science, University of Cagliari, Cagliari, ItalyMedical Genetics, Department of Medical Sciences and Public Health, University of Cagliari, Cagliari, ItalyComplex Structure of Pneumology, PO SS Trinità, ASSL Cagliari, ATS Sardegna, Cagliari, ItalyComplex Structure of Pneumology, PO SS Trinità, ASSL Cagliari, ATS Sardegna, Cagliari, Italy1Molecular Biology Service Laboratory, Department of Surgical Science, University of Cagliari, Cagliari, Italy2Liver Unit, Department of Internal Medicine, University Hospital of Cagliari, Cagliari, Italy2Liver Unit, Department of Internal Medicine, University Hospital of Cagliari, Cagliari, Italy2Liver Unit, Department of Internal Medicine, University Hospital of Cagliari, Cagliari, ItalyUnit of Oncology and Molecular Pathology, Department of Biomedical Sciences, University of Cagliari, Cagliari, ItalyDepartment of Medical Sciences and Public Health, University of Cagliari, Cagliari, ItalyAssociazione per l’Avanzamento della Ricerca per i Trapianti O.d.V., non profit organisation, Cagliari, ItalyUnit of Oncology and Molecular Pathology, Department of Biomedical Sciences, University of Cagliari, Cagliari, ItalyAssociazione per l’Avanzamento della Ricerca per i Trapianti O.d.V., non profit organisation, Cagliari, ItalyDepartment of Medical Sciences and Public Health, University of Cagliari, Cagliari, Italy2Liver Unit, Department of Internal Medicine, University Hospital of Cagliari, Cagliari, ItalyAimSARS-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.Method and MaterialsWe 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.ResultsMale 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-A*02:05, B*58:01, C*07:01, DRB1*03:01 [OR 0.1 (95% CI 0–0.6), Pc = 0.015] was absent in all 182 patients, while the HLA-C*04:01 allele and the three-loci haplotype HLA-A*30:02, B*14:02, C*08:02 [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].ConclusionThe data emerging from our study suggest that the extended haplotype HLA-A*02:05, B*58:01, C*07:01, DRB1*03:01 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.https://www.frontiersin.org/articles/10.3389/fimmu.2020.605688/fullhuman leukocyte antigenSARS-CoV-2 infectionimmunogenetic backgroundCOVID-19 severitySardinian populationalleles |
| spellingShingle | Roberto Littera Roberto Littera Marcello Campagna Silvia Deidda Goffredo Angioni Selene Cipri Selene Cipri Maurizio Melis Davide Firinu Simonetta Santus Alberto Lai Rita Porcella Sara Lai Stefania Rassu Rosetta Scioscia Federico Meloni Daniele Schirru William Cordeddu Marta Anna Kowalik Maria Serra Paola Ragatzu Mauro Giovanni Carta Stefano Del Giacco Angelo Restivo Simona Deidda Sandro Orrù Antonella Palimodde Roberto Perra Germano Orrù Maria Conti Cinzia Balestrieri Giancarlo Serra Simona Onali Francesco Marongiu Andrea Perra Andrea Perra Luchino Chessa Luchino Chessa Luchino Chessa Human Leukocyte Antigen Complex and Other Immunogenetic and Clinical Factors Influence Susceptibility or Protection to SARS-CoV-2 Infection and Severity of the Disease Course. The Sardinian Experience Frontiers in Immunology human leukocyte antigen SARS-CoV-2 infection immunogenetic background COVID-19 severity Sardinian population alleles |
| title | Human Leukocyte Antigen Complex and Other Immunogenetic and Clinical Factors Influence Susceptibility or Protection to SARS-CoV-2 Infection and Severity of the Disease Course. The Sardinian Experience |
| title_full | Human Leukocyte Antigen Complex and Other Immunogenetic and Clinical Factors Influence Susceptibility or Protection to SARS-CoV-2 Infection and Severity of the Disease Course. The Sardinian Experience |
| title_fullStr | Human Leukocyte Antigen Complex and Other Immunogenetic and Clinical Factors Influence Susceptibility or Protection to SARS-CoV-2 Infection and Severity of the Disease Course. The Sardinian Experience |
| title_full_unstemmed | Human Leukocyte Antigen Complex and Other Immunogenetic and Clinical Factors Influence Susceptibility or Protection to SARS-CoV-2 Infection and Severity of the Disease Course. The Sardinian Experience |
| title_short | Human Leukocyte Antigen Complex and Other Immunogenetic and Clinical Factors Influence Susceptibility or Protection to SARS-CoV-2 Infection and Severity of the Disease Course. The Sardinian Experience |
| title_sort | human leukocyte antigen complex and other immunogenetic and clinical factors influence susceptibility or protection to sars cov 2 infection and severity of the disease course the sardinian experience |
| topic | human leukocyte antigen SARS-CoV-2 infection immunogenetic background COVID-19 severity Sardinian population alleles |
| url | https://www.frontiersin.org/articles/10.3389/fimmu.2020.605688/full |
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