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

IF 2.9 4区医学 Q3 IMMUNOLOGY

Microbes and Infection Pub Date : 2025-11-01 Epub Date: 2025-12-03 DOI:10.1016/j.micinf.2025.105590

Zhenyu Yang, Da Liu, Huiqing Qiu, Yajuan Yin, Xiangbin Meng, Jiadong Xue, Li Zhang, Chao Chang, Jing Li, Chunli Shao, Shuanli Xin, Mengdan Miao

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引用次数: 0

Abstract

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.

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探索基因预测血浆组织蛋白酶与COVID-19之间的联系：易感性和严重程度的孟德尔随机研究

背景：组织蛋白酶在各种疾病的进展中起着至关重要的作用，包括癌症、神经退行性疾病以及涉及炎症和免疫调节的过程。2019冠状病毒病全球大流行凸显了进一步探索组织蛋白酶与病毒之间的相互作用及其对疾病进展的影响的必要性。方法：本研究采用孟德尔随机化方法分析特异性基因预测血浆组织蛋白酶与COVID-19结局（严重和非严重）之间的因果关系。利用全基因组关联研究的数据，我们评估了基因预测的血浆组织蛋白酶B、D、F和S水平与COVID-19易感性和严重程度的关系。结果：基因预测的循环组织蛋白酶S水平升高可能与COVID-19易感性风险降低相关（P < 0.05）。此外，尽管对COVID-19的易感性增加导致基因预测的循环组织蛋白酶F水平升高和基因预测的组织蛋白酶S水平降低似乎存在相关性（P < 0.05），但应谨慎解释这些关联。也有证据表明，COVID-19严重程度的进展与基因预测的循环组织蛋白酶F水平升高之间存在因果关系（P < 0.05）。然而，由于孟德尔随机化方法的固有局限性，需要进一步的研究来证实这些初步发现。结论：本研究强调了组织蛋白酶在COVID-19病理生理中的潜在作用，并提示调节这些酶的表达或活性可能影响易感性和疾病严重程度。这些发现为基因预测血浆组织蛋白酶与COVID-19之间的相互作用提供了新的视角，表明需要进一步研究这些发现背后的机制以及针对特定组织蛋白酶的干预措施在预防或治疗COVID-19中的潜在功效。

本文章由计算机程序翻译，如有差异，请以英文原文为准。

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来源期刊

Microbes and Infection 医学-病毒学

CiteScore

12.60

自引率

1.70%

发文量

审稿时长

40 days

期刊介绍： Microbes and Infection publishes 10 peer-reviewed issues per year in all fields of infection and immunity, covering the different levels of host-microbe interactions, and in particular: the molecular biology and cell biology of the crosstalk between hosts (human and model organisms) and microbes (viruses, bacteria, parasites and fungi), including molecular virulence and evasion mechanisms. the immune response to infection, including pathogenesis and host susceptibility. emerging human infectious diseases. systems immunology. molecular epidemiology/genetics of host pathogen interactions. microbiota and host "interactions". vaccine development, including novel strategies and adjuvants. Clinical studies, accounts of clinical trials and biomarker studies in infectious diseases are within the scope of the journal. Microbes and Infection publishes articles on human pathogens or pathogens of model systems. However, articles on other microbes can be published if they contribute to our understanding of basic mechanisms of host-pathogen interactions. Purely descriptive and preliminary studies are discouraged.