Severe COVID-19 disease is associated with genetic factors affecting plasma ACE2 receptor and CRP concentrations
Abstract A hyperinflammatory state with highly elevated concentrations of inflammatory biomarkers such as C-reactive protein (CRP) is a characteristic feature of severe coronavirus disease 2019 (COVID-19). To examine a potential role of common genetic factors that may influence COVID-19 outcomes, we...
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Nature Portfolio
2025-02-01
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| Series: | Scientific Reports |
| Online Access: | https://doi.org/10.1038/s41598-025-89306-4 |
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| author | Verena Vogi David Haschka Lukas Forer Simon Schwendinger Verena Petzer Stefan Coassin Ivan Tancevski Thomas Sonnweber Judith Löffler-Ragg Elisabeth Puchhammer-Stöckl Marianne Graninger Dominik Wolf Florian Kronenberg Johannes Zschocke Emina Jukic Günter Weiss |
| author_facet | Verena Vogi David Haschka Lukas Forer Simon Schwendinger Verena Petzer Stefan Coassin Ivan Tancevski Thomas Sonnweber Judith Löffler-Ragg Elisabeth Puchhammer-Stöckl Marianne Graninger Dominik Wolf Florian Kronenberg Johannes Zschocke Emina Jukic Günter Weiss |
| author_sort | Verena Vogi |
| collection | DOAJ |
| description | Abstract A hyperinflammatory state with highly elevated concentrations of inflammatory biomarkers such as C-reactive protein (CRP) is a characteristic feature of severe coronavirus disease 2019 (COVID-19). To examine a potential role of common genetic factors that may influence COVID-19 outcomes, we investigated whether individuals with a polygenic predisposition for a pro-inflammatory response (in the form of Polygenic Scores) are more likely to develop severe COVID-19. The innovative approach of polygenic scores to investigate genetic factors in COVID-19 severity should provide a comprehensive approach beyond single-gene studies. In our cohort of 156 patients of European ancestry, two overlapping Polygenic Scores (PGS) predicting a genetic predisposition to basal CRP concentrations were significantly different between non-severe and severe COVID-19 cases and were associated with less severe COVID-19 outcomes. Furthermore, specific single nucleotide polymorphisms (SNPs) that contribute to either of the two Polygenic Scores predicting basal CRP levels are associated with different traits that represent risk factors for COVID-19 disease initiation (ACE2 receptor, viral replication) and progression (CRP). We suggest that genetically determined enforced CRP formation may contribute to strengthening of innate immune responses and better initial pathogen control thereby reducing the risk of subsequent hyperinflammation and adverse course of COVID-19. |
| format | Article |
| id | doaj-art-a3a04f181db648f48db186615d81db01 |
| institution | Kabale University |
| issn | 2045-2322 |
| language | English |
| publishDate | 2025-02-01 |
| publisher | Nature Portfolio |
| record_format | Article |
| series | Scientific Reports |
| spelling | doaj-art-a3a04f181db648f48db186615d81db012025-02-09T12:29:57ZengNature PortfolioScientific Reports2045-23222025-02-0115111210.1038/s41598-025-89306-4Severe COVID-19 disease is associated with genetic factors affecting plasma ACE2 receptor and CRP concentrationsVerena Vogi0David Haschka1Lukas Forer2Simon Schwendinger3Verena Petzer4Stefan Coassin5Ivan Tancevski6Thomas Sonnweber7Judith Löffler-Ragg8Elisabeth Puchhammer-Stöckl9Marianne Graninger10Dominik Wolf11Florian Kronenberg12Johannes Zschocke13Emina Jukic14Günter Weiss15Institute of Human Genetics, Medical University InnsbruckDepartment of Internal Medicine II (Infectious Diseases, Immunology, Pneumology and Rheumatology), Medical University InnsbruckInstitute of Genetic Epidemiology, Medical University InnsbruckInstitute of Human Genetics, Medical University InnsbruckDepartment of Internal Medicine V (Hematology and Internistic Oncology), Medical University InnsbruckInstitute of Genetic Epidemiology, Medical University InnsbruckDepartment of Internal Medicine II (Infectious Diseases, Immunology, Pneumology and Rheumatology), Medical University InnsbruckDepartment of Internal Medicine II (Infectious Diseases, Immunology, Pneumology and Rheumatology), Medical University InnsbruckDepartment of Internal Medicine II (Infectious Diseases, Immunology, Pneumology and Rheumatology), Medical University InnsbruckDepartment of Virology, Medical University ViennaDepartment of Virology, Medical University ViennaDepartment of Internal Medicine V (Hematology and Internistic Oncology), Medical University InnsbruckInstitute of Genetic Epidemiology, Medical University InnsbruckInstitute of Human Genetics, Medical University InnsbruckInstitute of Human Genetics, Medical University InnsbruckDepartment of Internal Medicine II (Infectious Diseases, Immunology, Pneumology and Rheumatology), Medical University InnsbruckAbstract A hyperinflammatory state with highly elevated concentrations of inflammatory biomarkers such as C-reactive protein (CRP) is a characteristic feature of severe coronavirus disease 2019 (COVID-19). To examine a potential role of common genetic factors that may influence COVID-19 outcomes, we investigated whether individuals with a polygenic predisposition for a pro-inflammatory response (in the form of Polygenic Scores) are more likely to develop severe COVID-19. The innovative approach of polygenic scores to investigate genetic factors in COVID-19 severity should provide a comprehensive approach beyond single-gene studies. In our cohort of 156 patients of European ancestry, two overlapping Polygenic Scores (PGS) predicting a genetic predisposition to basal CRP concentrations were significantly different between non-severe and severe COVID-19 cases and were associated with less severe COVID-19 outcomes. Furthermore, specific single nucleotide polymorphisms (SNPs) that contribute to either of the two Polygenic Scores predicting basal CRP levels are associated with different traits that represent risk factors for COVID-19 disease initiation (ACE2 receptor, viral replication) and progression (CRP). We suggest that genetically determined enforced CRP formation may contribute to strengthening of innate immune responses and better initial pathogen control thereby reducing the risk of subsequent hyperinflammation and adverse course of COVID-19.https://doi.org/10.1038/s41598-025-89306-4 |
| spellingShingle | Verena Vogi David Haschka Lukas Forer Simon Schwendinger Verena Petzer Stefan Coassin Ivan Tancevski Thomas Sonnweber Judith Löffler-Ragg Elisabeth Puchhammer-Stöckl Marianne Graninger Dominik Wolf Florian Kronenberg Johannes Zschocke Emina Jukic Günter Weiss Severe COVID-19 disease is associated with genetic factors affecting plasma ACE2 receptor and CRP concentrations Scientific Reports |
| title | Severe COVID-19 disease is associated with genetic factors affecting plasma ACE2 receptor and CRP concentrations |
| title_full | Severe COVID-19 disease is associated with genetic factors affecting plasma ACE2 receptor and CRP concentrations |
| title_fullStr | Severe COVID-19 disease is associated with genetic factors affecting plasma ACE2 receptor and CRP concentrations |
| title_full_unstemmed | Severe COVID-19 disease is associated with genetic factors affecting plasma ACE2 receptor and CRP concentrations |
| title_short | Severe COVID-19 disease is associated with genetic factors affecting plasma ACE2 receptor and CRP concentrations |
| title_sort | severe covid 19 disease is associated with genetic factors affecting plasma ace2 receptor and crp concentrations |
| url | https://doi.org/10.1038/s41598-025-89306-4 |
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