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Pathway-Based Mendelian Randomization for Pre-Infection IL-6 Levels Highlights Its Role in Coronavirus Disease.
- Source :
- Genes; Jul2024, Vol. 15 Issue 7, p889, 10p
- Publication Year :
- 2024
-
Abstract
- Objectives: Interleukin 6 (IL-6) levels at hospital admission have been suggested for disease prognosis, and IL-6 antagonists have been suggested for the treatment of patients with severe COVID-19. However, less is known about the relationship between pre-COVID-19 IL-6 levels and the risk of severe COVID-19. To fill in this gap, here we extensively investigated the association of genetically instrumented IL-6 pathway components with the risk of severe COVID-19. Methods: We used a two-sample Mendelian randomization study design and retrieved genetic instruments for blood biomarkers of IL-6 activation, including IL-6, soluble IL-6 receptor, IL-6 signal transducer, and CRP, from respective large available GWASs. To establish associations of these instruments with COVID-19 outcomes, we used data from the Host Genetics Initiative and GenOMICC studies. Results: Our analyses revealed inverse associations of genetically instrumented levels of IL-6 and its soluble receptor with the risk of developing severe disease (OR = 0.60 and 0.94, respectively). They also demonstrated a positive association of severe disease with the soluble signal transducer level (OR = 1.13). Only IL-6 associations with severe COVID-19 outcomes reached the significance threshold corrected for multiple testing (p < 0.003; with COVID-19 hospitalization and critical illness). Conclusions: These potential causal relationships for pre-COVID-19 IL-6 levels with the risk of developing severe symptoms provide opportunities for further evaluation of these factors as prognostic/preventive markers of severe COVID-19. Further studies will need to clarify whether the higher risk for a severe disease course with lower baseline IL-6 levels may also extend to other infectious diseases. [ABSTRACT FROM AUTHOR]
- Subjects :
- COVID-19
PROGNOSIS
INTERLEUKIN-6
COMMUNICABLE diseases
CRITICALLY ill
Subjects
Details
- Language :
- English
- ISSN :
- 20734425
- Volume :
- 15
- Issue :
- 7
- Database :
- Complementary Index
- Journal :
- Genes
- Publication Type :
- Academic Journal
- Accession number :
- 178689367
- Full Text :
- https://doi.org/10.3390/genes15070889