TYK2 as a therapeutic target for COVID-19: Mendelian randomization study.

In this study, the potential effects of Tyrosine kinase 2 (TYK2) inhibition on COVID-19 outcomes was explored by assessing the causal association of the expression of TYK2 and COVID-19 outcomes with a two-sample Mendelian randomization (MR) design using summary statistics from genome-wide association studies (GWAS) and colocalization analysis. The MR analysis showed that the increase in gene expression of TYK2 was associated with a higher risk of critical illness COVID-19, hospitalized COVID-19, and SARS-CoV-2 infection with inverse-variance weighted method. The mediation analysis showed that the increased risk of COVID-19 by TYK2 expression is partly mediated by the increased C-C motif ligand 2 (CCL2) and intercellular adhesion molecule-1 (ICAM1) levels. The study provided suggestive evidence that TYK2 inhibition reduces the risk of COVID-19, and proposed TYK2 as a drug target for COVID-19 treatment.