Researchers have successfully identified 68 protein-coding genes associated with risk of severe COVID-19.
This was successfully confirmed with the aid of a unique artificial intelligence (AI) platform which was used to analyze the genomes of 929 patients from the UK Biobank who expressed severe response to SARS-CoV-2.
Knowledge of these genes will significantly support healthcare experts in the identity of patients who are at greatest risk of expressing severe forms of COVID-19. More so, they can inform the development of biomarker driven tests, targeted shielding and new therapeutic strategies, with the sole purpose of identifying high-risk individuals, reduction of disease burden and improving survival rates.
The heterogenous characteristic of COVID-19 limits establishment of Genome Wide Association Studies (GWAS), this limitation makes it difficult to clearly explain the wide range of symptoms and impacts of predisposing comorbidities associated with the disease. All of this limitations were surmounted by analyzing combinations of genetic features, which is not possible with existing GWAS approaches.
The analysis was successfully conducted with the aid of a combinatorial (high-order epistasis) analysis approach, the findings was that 68 protein-coding genes were identified to be associated with severe COVID-19, nine of which have been linked to differential response to SARS-CoV-2. These 68 genes include a number of druggable protein targets and pathways, of these, 9 are targeted by drugs that have reached at least Phase I clinical trials.
Expanding research analysis to successfully confirm the differences between severe and mild COVID-19 cases is key to providing an additional layer of validation to the results from this study.
Systematic remodeling, leaky vasculature and micro-clotting can cause severe issues in COVID-19 patients in lungs as well as other organs. A number of the genes identifies relate to lipid programming, beta-catenin and protein kinase C signaling whose processes converge in a central pathway involved in plasma membrane repair, clotting and wound healing and this are positive indicators of progress. Calcium ion activation a known serum biomarker associated with severe COVID-19 and acute respiratory distress syndrome (ARDS) is a major driver of this pathway. Further analysis are on the way to validate 12 genes associated with dysfunctional immune response that are the first hint at a potential genetic signature for enhanced risk of flipping into a sever disease state.