Exploring the link between genetically predicted plasma cathepsins and COVID-19: A mendelian randomization study of...

Cathepsin play a crucial role in the progression of various diseases, including cancer, neurodegenerative disorders, and processes involving inflammation and immune modulation. The global pandemic of COVID-19 has heightened the need for further exploration into the interactions between cathepsin and the virus, and their impact on disease progression.

This study employed Mendelian randomization to analyze the causal relationships between specific genetically predicted plasma cathepsin and COVID-19 outcomes, both severe and non-severe. Using data from genome-wide association studies, we evaluated the associations of genetically predicted plasma levels of cathepsin B, D, F, and S with susceptibility to and severity of COVID-19.

An increase in genetically predicted circulating cathepsin S levels might be associated with a reduced susceptibility risk to COVID-19 (P < 0.05). Furthermore, while there appears to be a correlation where increased susceptibility to COVID-19 leads to elevated levels of genetically predicted circulating cathepsin F and a reduction in genetically predicted cathepsin S levels (P < 0.05), these associations should be interpreted with caution. There is also suggestive evidence of a causal association between the progression of COVID-19 severity and increased levels of genetically predicted circulating cathepsin F (P < 0.05). However, due to the inherent limitations of the Mendelian randomization approach, further studies are warranted to substantiate these initial findings.

This study highlights the potential role of cathepsin in the pathophysiology of COVID-19 and suggests that modulating the expression or activity of these enzymes could influence susceptibility and disease severity. These findings provide a new perspective on the interaction between genetically predicted plasma cathepsin and COVID-19, suggesting further research is needed to explore the mechanisms behind these findings and the potential efficacy of interventions targeting specific cathepsin in the prevention or treatment of COVID-19.