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

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 <i>IL6</i>, <i>IL6R</i>, <i>IL1α</i>, <i>IL1R</i>, <i>IFNγ</i>, <i>TNFα</i>, <i>CRP</i>, <i>VDR</i>, <i>VDBP</i>, and <i>ACE2</i> 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.