Identification of shared genes and possible therapeutic target between systemic lupus erythematosus and COVID-19

ABSTRACT

Background/purpose: Coronavirus disease 2019 (COVID-19) has led to a rapid increase in mortality worldwide. Systemic lupus erythematosus (SLE) was a high-risk factor for severe acute respiratory syndrome coronavirus 2 (SARS-CoV- 2) infection, Whereas the molecular mechanisms underlying SLE and CVOID-19 are not well understood. This study aims to discover the common molecular mechanisms and genetic biomarkers of SLE and COVID-19, providing new ideas for the treatment of COVID-19. Method(s) RNA sequencing data of peripheral blood mononuclear cells (PBMC) from 6 SLE datasets and 8 COVID-19 datasets were obtained from the GEO database. Highly related modular genes associated with COVID-19 and SLE were identified by weighted gene co-expression network analysis (WGCNA). The differentially expressed genes (DEGs) between patients and healthy controls (HCs) were identified by the limma package. Common shared DEGs from COVID-19 and SLE were identified. Cytoscape and MCODE plugin were utilized for exploring the protein-protein interaction network (PPI) and identifying shared hub genes. Potential biological functions and pathways were also explored from the common DEGs. For better analysis of detailed biological mechanisms, both xCell algorithm and the cMap in CLUE (https//clue.io/) were utilized for discovering immune cell infiltration and predicting potential drugs that negatively regulate the highly expressed genes. Result(s) With identified 498 up-regulated common DEGs in SLE and COVID-19 related genes, total 11 and 13 gene modules of SLE and COVID-19 were identified espectively After overlapping differential genes, the final intersection gene set contains 218 genes. The PPI, especially the functional subnet module consists of upregulated genes by MCODE showed a great deal IFN related genes involved in the regulation of immunity. GO biological processes also showed possible functions were defense response to virus and mitotic cell cycle. Moreover, changes of most immune cells were strongly consistent between SLE and COVID-19. CDK inhibitors identified may be more likely to inhibit two diseases. Conclusion(s) Our study examined in detail the common molecular mechanisms of SLE and COVID-19, in which cellular response to cytokine stimulus, like regulating IFN, which might be the key target of both diseases. CDK is associated with the progression of SLE and COVID-19, which may be the potential therapeutic drug for SLE patients with COVID-19 infection.