Publication date: Jul 24, 2025
The severity of COVID-19 disease can vary greatly, influenced by genetic factors and comorbid conditions that may increase mortality. This study has examined potential genetic influences on the disease for a young adult aged 36 years with T2DM-CAD multi-morbidity with severe COVID-19 disease and in-hospital mortality using whole-exome sequencing. The patient exhibited a constellation of severe symptoms and abnormality in several biochemical markers associated with COVID-19 disease and comorbid conditions. A total of 756 variants were discovered in the patient, including several rare and novel variants associated with immune pathways. A set of 10 unique candidate variants in 10 distinct genes were identified with nine variants located within genes associated with the COVID-19 panel (HLA-DRB1, IL23R, PRKDC, RNF31, SLC37A4, TAP2, TCIRG1, TCN2, and TPP2), while one variant was found in a gene (PAX6) from Diabetes panel. Enrichment analysis showed that the top three enriched GO biological processes were a response to stimulus (n = 23, p = 6. 8E-3), immune system process (n = 22, p = 3. 6E-12), and regulation of immune system process (n = 19, p = 1. 57E-11). The Maximal Clique Centrality algorithm identified HLA-DRB1 as a prominent hub gene and potential loss-of-function mutation in HLA-DRB1, suggests a compromised antigen presentation mechanism within this patient.
| Concepts | Keywords |
|---|---|
| Diabetes | case report |
| Hospital | Covid-19 |
| Maximal | gene variants |
| Pathogenic | genetic biomarkers |
| Rnf31 | immunity |
| whole exome sequencing |
Semantics
| Type | Source | Name |
|---|---|---|
| disease | MESH | COVID-19 |
| disease | MESH | morbidity |
| disease | IDO | algorithm |
| drug | DRUGBANK | Huperzine B |
| disease | MESH | Long Covid |