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

## TL;DR

This study explores how genes related to neutrophil extracellular traps may link post-COVID-19 and Guillain-Barre syndrome, identifying potential biomarkers and drugs.

## Contribution

The study identifies co-expressed genes and molecular mechanisms linking post-COVID-19 and Guillain-Barre syndrome through NET-related genes.

## Key findings

- 3254 and 692 differentially expressed genes were identified in COVID-19 and GBS datasets, with 145 co-expressed genes.
- MMP9, CAMP, and CASP1 were identified as NET-related genes with good discriminatory capacity in both conditions.
- Neutrophils and macrophages were found to be co-upregulated immune cells in both diseases, and 10 candidate drugs were identified.

## Abstract

Neutrophil 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.

By 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.

In 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.

In conclusion, MMP9, CASP1, and CAMP were identified as promising biomarkers and potential targets for therapy of post-COVID-19 GBS.