A Machine Learning Approach to Understanding the Genetic Role in COVID-19 Prognosis: The Influence of Gene Polymorphisms Related to Inflammation, Vitamin D, and ACE2

DOI record: { "DOI": "10.3390/ijms26167975", "ISSN": [ "1422-0067" ], "URL": "http://dx.doi.org/10.3390/ijms26167975", "abstract": "<jats:p>The genetic background influences the outcomes of COVID-19. This study aimed to evaluate the incidence of polymorphisms in genes linked to the RAAS system, cytokine production, and vitamin D on COVID-19 severity, with the goal of gaining a deeper understanding of the genetic etiology related to COVID-19. This study involved 338 COVID-19 patients and employed machine learning methods to identify the genetic variants that most significantly affect COVID-19 severity. The results revealed that polymorphisms in the IL6, IL6R, IL1α, IL1R, IFNγ, TNFα, CRP, VDR, VDBP, and ACE2 genes are the most significant genetic factors influencing COVID-19 prognosis, particularly in terms of the risks of COVID-19 pneumonia, mortality, rehospitalization, and associated mortality. The machine learning methods achieved an AUC of 0.86 for predicting COVID-19 pneumonia, mortality, and mortality related to rehospitalization, as well as an AUC of 0.85 for rehospitalization within the first year. These results confirm the crucial role of genetic background in COVID-19 prognosis, facilitating the identification of patients at increased risk. In summary, this research demonstrates that genetics-driven machine learning models can pinpoint patients at heightened risk by primarily focusing on genetic variants associated with ACE2, inflammation, and vitamin D.</jats:p>", "alternative-id": [ "ijms26167975" ], "author": [ { "affiliation": [ { "name": "Department of Pneumonology, University Clinical Hospital of Valladolid, 47003 Valladolid, Spain" } ], "family": "Jaurrieta-Largo", "given": "Sofía", "sequence": "first" }, { "ORCID": "https://orcid.org/0000-0002-2247-9679", "affiliation": [ { "name": "Department of Internal Medicine, Río Hortega University Hospital, 47012 Valladolid, Spain" }, { "name": "Department of Medicine, Faculty of Medicine, University of Valladolid, 47003 Valladolid, Spain" } ], "authenticated-orcid": false, "family": "Miramontes-González", "given": "José Pablo", "sequence": "additional" }, { "affiliation": [ { "name": "Department of Internal Medicine, Río Hortega University Hospital, 47012 Valladolid, Spain" }, { "name": "Department of Medicine, Faculty of Medicine, University of Valladolid, 47003 Valladolid, Spain" } ], "family": "Corral-Gudino", "given": "Luis", "sequence": "additional" }, { "affiliation": [ { "name": "Department of Internal Medicine, Río Hortega University Hospital, 47012 Valladolid, Spain" } ], "family": "Gabella-Martín", "given": "Miriam", "sequence": "additional" }, { "affiliation": [ { "name": "Department of Internal Medicine, Río Hortega University Hospital, 47012 Valladolid, Spain" } ], "family": "Pérez-Arroyo", "given": "Sofía", "sequence": "additional" }, { "ORCID": "https://orcid.org/0000-0003-4603-9034", "affiliation": [ { "name": "Medical Analysis Expert Group, Castilla-La Mancha Institute of Health Research (IDISCAM), 45071 Toledo, Spain" }, { "name": "Medical Analysis Expert Group, Institute of Technology, University of Castilla-La Mancha, 16071 Cuenca, Spain" } ], "authenticated-orcid": false, "family": "Torres", "given": "Ana M.", "sequence": "additional" }, { "affiliation": [ { "name": "Medical Analysis Expert Group, Castilla-La Mancha Institute of Health Research (IDISCAM), 45071 Toledo, Spain" }, { "name": "Medical Analysis Expert Group, Institute of Technology, University of Castilla-La Mancha, 16071 Cuenca, Spain" } ], "family": "Mateo", "given": "Jorge", "sequence": "additional" }, { "ORCID": "https://orcid.org/0000-0002-1723-217X", "affiliation": [ { "name": "Department of Internal Medicine, Río Hortega University Hospital, 47012 Valladolid, Spain" }, { "name": "Department of Medicine, Faculty of Medicine, University of Valladolid, 47003 Valladolid, Spain" } ], "authenticated-orcid": false, "family": "Pérez-Castrillón", "given": "José Luis", "sequence": "additional" }, { "ORCID": "https://orcid.org/0000-0001-7699-4388", "affiliation": [ { "name": "Department of Cell Biology, Faculty of Medicine, University of Valladolid, 47005 Valladolid, Spain" }, { "name": "Unit of Excellence IOBA, University of Valladolid, 47005 Valladolid, Spain" } ], "authenticated-orcid": false, "family": "Usategui-Martín", "given": "Ricardo", "sequence": "additional" } ], "container-title": "International Journal of Molecular Sciences", "container-title-short": "IJMS", "content-domain": { "crossmark-restriction": false, "domain": [] }, "created": { "date-parts": [ [ 2025, 8, 18 ] ], "date-time": "2025-08-18T16:22:33Z", "timestamp": 1755534153000 }, "deposited": { "date-parts": [ [ 2025, 8, 19 ] ], "date-time": "2025-08-19T07:57:35Z", "timestamp": 1755590255000 }, "funder": [ { "award": [ "GRS 2255/A/20", "GRS COVID91/A/20" ], "name": "Gerencia Regional de Salud, Castilla y León, Spain" }, { "name": "Institute of Technology" }, { "name": "Chair of Artificial Intelligence" }, { "name": "Castilla-La Mancha Institute of Health Research" } ], "indexed": { "date-parts": [ [ 2025, 8, 19 ] ], "date-time": "2025-08-19T08:10:09Z", "timestamp": 1755591009166, "version": "3.43.0" }, "is-referenced-by-count": 0, "issue": "16", "issued": { "date-parts": [ [ 2025, 8, 18 ] ] }, "journal-issue": { "issue": "16", "published-online": { "date-parts": [ [ 2025, 8 ] ] } }, "language": "en", "license": [ { "URL": "https://creativecommons.org/licenses/by/4.0/", "content-version": "vor", "delay-in-days": 0, "start": { "date-parts": [ [ 2025, 8, 18 ] ], "date-time": "2025-08-18T00:00:00Z", "timestamp": 1755475200000 } } ], "link": [ { "URL": "https://www.mdpi.com/1422-0067/26/16/7975/pdf", "content-type": "unspecified", "content-version": "vor", "intended-application": "similarity-checking" } ], "member": "1968", "original-title": [], "page": "7975", "prefix": "10.3390", "published": { "date-parts": [ [ 2025, 8, 18 ] ] }, "published-online": { "date-parts": [ [ 2025, 8, 18 ] ] }, "publisher": "MDPI AG", "reference": [ { "DOI": "10.1056/NEJMoa2002032", "article-title": "Clinical Characteristics of Coronavirus Disease 2019 in China", "author": "Guan", "doi-asserted-by": "crossref", "first-page": "1708", "journal-title": "N. 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