AUTHOR=Su Jie-Hua , Lin Dan-Yu , Liu Xiao-Huan , Zhang Jie-Li , Li Zhong-Gui , Tao En-Xiang , Huang Kai-Xun 

TITLE=Identifying potential co-expressed genes and molecular mechanisms linking post-COVID-19 and Guillain-Barre syndrome through neutrophil extracellular trap-related genes

JOURNAL=Frontiers in Neurology

VOLUME=Volume 16 - 2025

YEAR=2025

URL=https://www.frontiersin.org/journals/neurology/articles/10.3389/fneur.2025.1447725

DOI=10.3389/fneur.2025.1447725

ISSN=1664-2295

ABSTRACT=IntroductionNeutrophil extracellular traps (NETs) play a pivotal role in immunity and autoinflammatory disease, leading us to hypothesize that NETs are crucial in Guillain-Barre Syndrome (GBS) after SARS-CoV-2 infection.MethodsBy collecting six Gene Expression Omnibus (GEO) datasets from the GEO database and dividing them into discovery and validation sets, we screened differentially expressed genes (DEGs) within the discovery set, with further analyses using functional enrichment analysis. Using single-sample gene set enrichment analysis (ssGSEA), we assessed immune cell infiltration in both coronavirus disease 2019 (COVID-19) and GBS datasets. NETs-related genes (NETRGs) were identified through a protein–protein interaction (PPI) network and NETs gene datasets. Finally, candidate drugs were screened using Connectivity Map.ResultsIn this study, a total of 3254 DEGs were identified from the COVID-19 dataset, and 692 DEGs were obtained from the GBS dataset. Among these, 145 co-expressed DEGs were obtained. Bioinformatics functional analysis indicated that co-expressed DEGs were predominantly gathered in immune-related and inflammatory response pathways. Employing various algorithms, we identified MMP9, CAMP, and CASP1 as NETRGs, demonstrating good discriminatory capacity in COVID-19 and GBS. Notably, neutrophils and macrophages were identified as co-upregulated differential immune infiltrating cells significantly associated with both COVID-19 and GBS. Moreover, we identified 10 candidate drugs for patients with post-COVID-19 GBS.ConclusionIn conclusion, MMP9, CASP1, and CAMP were identified as promising biomarkers and potential targets for therapy of post-COVID-19 GBS.