Vogi Verena, Haschka David, Forer Lukas, Schwendinger Simon, Petzer Verena, Coassin Stefan, Tancevski Ivan, Sonnweber Thomas, Löffler-Ragg Judith, Puchhammer-Stöckl Elisabeth, Graninger Marianne, Wolf Dominik, Kronenberg Florian, Zschocke Johannes, Jukic Emina, Weiss Günter
Institute of Human Genetics, Medical University Innsbruck, Innsbruck, 6020, Austria.
Department of Internal Medicine II (Infectious Diseases, Immunology, Pneumology and Rheumatology), Medical University Innsbruck, Innsbruck, 6020, Austria.
Sci Rep. 2025 Feb 8;15(1):4708. doi: 10.1038/s41598-025-89306-4.
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.
炎症生物标志物（如C反应蛋白，CRP）浓度高度升高的高炎症状态是重症2019冠状病毒病（COVID-19）的一个特征。为了研究可能影响COVID-19预后的常见遗传因素的潜在作用，我们调查了具有促炎反应多基因易感性（以多基因分数形式）的个体是否更易发生重症COVID-19。采用多基因分数这一创新方法来研究COVID-19严重程度中的遗传因素，应能提供一种超越单基因研究的全面方法。在我们的156名欧洲血统患者队列中，预测基础CRP浓度遗传易感性的两个重叠多基因分数（PGS）在非重症和重症COVID-19病例之间存在显著差异，且与较轻的COVID-19预后相关。此外，对预测基础CRP水平的两个多基因分数之一有贡献的特定单核苷酸多态性（SNP），与代表COVID-19发病（ACE2受体、病毒复制）和进展（CRP）危险因素的不同特征相关。我们认为，基因决定的CRP生成增强可能有助于加强先天免疫反应和更好地进行初始病原体控制，从而降低后续发生高炎症和COVID-19不良病程的风险。
