VCL/ICAM-1 pathway is associated with lung inflammatory damage in SARS-CoV-2 Omicron infection

SARS-CoV-2 variants present diverse clinical manifestations, necessitating deeper insights into their pathogenic effects. This study employs multi-omics approaches to investigate the molecular mechanisms underlying SARS-CoV-2 infection, focusing on vascular damage. Plasma proteomic analysis of unvaccinated participants infected with Omicron BA.2.76 or ancestral variants identifies key signaling pathways associated with endothelial dysfunction, with the vinculin (VCL) pathway emerging as a hallmark of Omicron infections, contributing to lung exudation. Metabolomic analysis of plasma samples from the same cohort reveals disruptions in immune function, cell membrane integrity, and metabolic processes, including altered tricarboxylic acid cycle and glycolysis pathways. An integrated analysis of proteomic and metabolomic data underscores the role of VCL in inflammation and extravasation, highlighting its interactions with adhesion molecules and inflammatory metabolites. A validation cohort of plasma samples from Omicron-infected participants confirms this association by replicating proteomic analysis, showing elevated VCL levels correlated with inflammatory markers. Functional studies in a male rat model of lung injury demonstrate that anti-VCL intervention reduces plasma VCL levels, mitigates alveolar edema, and restores alveolar-capillary barrier integrity, as assessed by histological staining and electron microscopy, thereby illustrating VCL modulation's impact on vascular leakage and extravasation. These findings establish VCL as a potential therapeutic target for mitigating vascular complications in SARS-CoV-2 infections.

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Publication Details

Journal
Nature Communications
Published
2025-04-23
DOI
https://doi.org/10.1038/s41467-025-59145-y
Citations
2
Primary Topic
COVID-19 Clinical Research Studies
Type
article
Field-Weighted Citation Impact
2.79
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article

VCL/ICAM-1 pathway is associated with lung inflammatory damage in SARS-CoV-2 Omicron infection

Qian Guo, Peiyan Zheng, Baoqing Sun, Mingshan Xue et al.
2 citations
Nature Communications
COVID-19 Clinical Research Studies
2.79
article

VCL/ICAM-1 pathway is associated with lung inflammatory damage in SARS-CoV-2 Omicron infection

Qian Guo, Peiyan Zheng, Baoqing Sun, Mingshan Xue, Zhiping Deng, Hongman Wang, Huimin Huang, Youxia Li, Susu Fan, Meixia Zhang, Fengyu Hu, Zhiwei Lin, Qiurong Hu, Lu Li, Hui‐Qi Qu, Quan Yuan, Håkon Håkonarson, Xiaowen Wang, Qianyue Yang, Xiaoping Tang, Yue Wen, Peixin Liu, Xin Zhao, Jia-Hong Chen, Qiyuan Wu, Lijun Su, C.-Y. Jiang, Ning Li
article en
2 citations

Abstract

SARS-CoV-2 variants present diverse clinical manifestations, necessitating deeper insights into their pathogenic effects. This study employs multi-omics approaches to investigate the molecular mechanisms underlying SARS-CoV-2 infection, focusing on vascular damage. Plasma proteomic analysis of unvaccinated participants infected with Omicron BA.2.76 or ancestral variants identifies key signaling pathways associated with endothelial dysfunction, with the vinculin (VCL) pathway emerging as a hallmark of Omicron infections, contributing to lung exudation. Metabolomic analysis of plasma samples from the same cohort reveals disruptions in immune function, cell membrane integrity, and metabolic processes, including altered tricarboxylic acid cycle and glycolysis pathways. An integrated analysis of proteomic and metabolomic data underscores the role of VCL in inflammation and extravasation, highlighting its interactions with adhesion molecules and inflammatory metabolites. A validation cohort of plasma samples from Omicron-infected participants confirms this association by replicating proteomic analysis, showing elevated VCL levels correlated with inflammatory markers. Functional studies in a male rat model of lung injury demonstrate that anti-VCL intervention reduces plasma VCL levels, mitigates alveolar edema, and restores alveolar-capillary barrier integrity, as assessed by histological staining and electron microscopy, thereby illustrating VCL modulation's impact on vascular leakage and extravasation. These findings establish VCL as a potential therapeutic target for mitigating vascular complications in SARS-CoV-2 infections.

Nature CommunicationsVol. 16(1)
Children's Hospital of Philadelphia (US), University of Iceland (IS), Zunyi Medical University (CN), Guangzhou Experimental Station (CN), First Affiliated Hospital of Guangzhou Medical University (CN), Zhuhai People's Hospital (CN), Zigong First People's Hospital (CN), State Key Laboratory of Respiratory Disease (CN), Guangzhou Eighth People's Hospital (CN), University of Pennsylvania (US), Guangzhou Medical University (CN)
Good health and well-being
Openalex Percentile: Top 11%
COVID-19 Clinical Research Studies
2.79
DOIOpen Access PDFOpenAlex
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