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TYK2 as a therapeutic target for COVID-19: Mendelian randomization study
1Drug Clinical Trial Center, Gansu Wuwei Tumor Hospital, 16 Xuanwu Road, Wuwei, Gansu, China.
The New Microbiologica
|December 23, 2025
Summary
Tyrosine kinase 2 (TYK2) gene expression increases COVID-19 risk, including critical illness and hospitalization. Inhibiting TYK2 may reduce these risks, suggesting TYK2 as a potential therapeutic target for COVID-19 treatment.
Area of Science:
- Immunology
- Genetics
- Infectious Diseases
Background:
- Tyrosine kinase 2 (TYK2) plays a role in immune signaling pathways.
- Understanding genetic factors influencing COVID-19 severity is crucial for developing effective treatments.
Purpose of the Study:
- To investigate the causal relationship between Tyrosine kinase 2 (TYK2) gene expression and COVID-19 outcomes.
- To explore TYK2 as a potential drug target for mitigating COVID-19 severity.
Main Methods:
- Utilized a two-sample Mendelian randomization (MR) design.
- Employed summary statistics from genome-wide association studies (GWAS).
- Performed colocalization and mediation analyses.
Main Results:
- Increased TYK2 gene expression was causally associated with higher risks of critical illness COVID-19, hospitalized COVID-19, and SARS-CoV-2 infection.
- Mediation analysis indicated that C-C motif ligand 2 (CCL2) and intercellular adhesion molecule-1 (ICAM1) partially mediate the increased COVID-19 risk associated with TYK2 expression.
- Suggestive evidence supports TYK2 inhibition as a strategy to reduce COVID-19 risk.
Conclusions:
- TYK2 is implicated in increasing the risk and severity of COVID-19.
- TYK2 inhibition presents a promising therapeutic avenue for managing COVID-19.
- Targeting TYK2 could offer a novel approach to COVID-19 treatment and prevention.
