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Microbes Infect
. 2025 Dec 3:105590.
doi: 10.1016/j.micinf.2025.105590. Online ahead of print. Exploring the Link Between Genetically Predicted Plasma Cathepsins and COVID-19: A Mendelian Randomization Study of Susceptibility and Severity
Mengdan Miao 1 , Da Liu 2 , Huiqing Qiu 2 , Yajuan Yin 2 , Xiangbin Meng 2 , Jiadong Xue 3 , Li Zhang 4 , Chao Chang 1 , Jing Li 5 , Chunli Shao 6 , Shuanli Xin 7
Affiliations
Background: 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.
Methods: 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.
Results: 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.
Conclusion: 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.
Keywords: COVID-19; GWAS; Mendelian randomization; cathepsin; the Severe Acute Respiratory Syndrome Coronavirus 2.
. 2025 Dec 3:105590.
doi: 10.1016/j.micinf.2025.105590. Online ahead of print. Exploring the Link Between Genetically Predicted Plasma Cathepsins and COVID-19: A Mendelian Randomization Study of Susceptibility and Severity
Mengdan Miao 1 , Da Liu 2 , Huiqing Qiu 2 , Yajuan Yin 2 , Xiangbin Meng 2 , Jiadong Xue 3 , Li Zhang 4 , Chao Chang 1 , Jing Li 5 , Chunli Shao 6 , Shuanli Xin 7
Affiliations
- PMID: 41349954
- DOI: 10.1016/j.micinf.2025.105590
Background: 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.
Methods: 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.
Results: 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.
Conclusion: 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.
Keywords: COVID-19; GWAS; Mendelian randomization; cathepsin; the Severe Acute Respiratory Syndrome Coronavirus 2.