Publication date: May 27, 2026
The coronavirus disease 2019 (COVID-19) ranges from asymptomatic to very severe infection and death, largely depending on host factors, including genetics. We have investigated clinical and genetic data from 200 COVID-19 patients to search for factors predisposing to increased disease severity. Patients were divided into non-hospitalized mild/pauci-symptomatic and hospitalized severe. An interpretable Machine Learning approach was applied to blood biomarkers while genome-wide associations were performed for COVID-19 severity. Finally, a possible causal role of chronic low-grade inflammation on COVID-19 severity was searched by Mendelian Randomization. A high severity predictive role was observed in our sample by Machine Learning for the C-Reactive Protein measured in the course of SARS-CoV-2 infection (iCRP). This was also suggested by evidence of association with variants known to be involved in the CRP levels in the general population (pCRP). Finally, a possible causal role of chronic low-grade inflammation on COVID-19 severity could be shown by Mendelian Randomization using publicly available summary statistics of two COVID-19 Genome-Wide Association Studies. Consistent with previous results, a predictive role of CRP levels on COVID-19 severity was detected in our sample. Furthermore, Mendelian Randomization supported a causal role of genetically predicted chronic CRP levels.
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| Concepts | Keywords |
|---|---|
| Coronavirus | C-Reactive Protein |
| Covid | COVID-19 severity prediction |
| Death | CRP causal role |
| Genetics | Interpretable Machine Learning |
| Mild | Mendelian Randomization |
| TFEB |
Semantics
| Type | Source | Name |
|---|---|---|
| disease | MESH | COVID-19 |
| disease | MESH | death |
| disease | MESH | inflammation |
| pathway | REACTOME | SARS-CoV-2 Infection |
| disease | MESH | Long Covid |
| pathway | REACTOME | Reproduction |
| disease | MESH | included |
| disease | MESH | Infections |
| disease | MESH | Severe Acute Respiratory Syndrome |
| disease | MESH | asymptomatic infections |
| disease | MESH | interstitial pneumonia |
| disease | MESH | cytokine storm |
| disease | MESH | acute respiratory distress syndrome |
| disease | MESH | viral infections |
| disease | MESH | genetic predisposition |
| disease | MESH | rhinitis |
| disease | MESH | fever |