Bioinformatics and system biology approach to identify the influences of COVID-19 on primary sjogren's syndrome patients

ABSTRACT

Background: Primary Sjogren's syndrome (pSS) is a chronic, systemic, inflammatory autoimmune disease in which existing studies have found the presence of pSS-specific antibodies anti-SSA/ Ro in acute infection with COVID-19.1 The emergence of this phenomenon makes us aware that in the context of the long-term epidemic of COVID-19, it is necessary to further study the molecular mechanisms of the high susceptibility of pSS patients to COVID-19. Method(s) The gene expression profiles of 8 COVID-19 datasets and 5 pSS datasets were downloaded from the Gene Expression Omnibus (GEO) database. The differentially expressed genes (DEGs) between COVID-19 and PSS were identified using the limma software package and Weighted Gene Co-expression Network Analysis (WGCNA). A Venn diagram was used to discover common upregulated DEGs. To explore the possible pathogenesis of both diseases, common signaling pathways were explored by enriching DEGs using Gene Ontology (GO) and the Kyoto Gene and Genome Encyclopedia (KEGG) pathway. Protein-protein interactions (PPIs) were established to identify hub genes and key modules. The analysis of key gene expression characteristics by The Connectivity Map was used to predict potentially effective drugs. Finally, the CIBERSORT method was used to comprehensively evaluate the immune infiltrates of patients with COVID-19 and PSS to study the mechanisms that may have a common immune response or immune cell infiltration. Result(s) A total of 82 upregulated DEGs were identified in both COVID-19 and PSS (Figure 1 A-E). Functional enrichment analysis illustrated the important role of enhanced signaling pathways in response to virus defense and interferon-alpha in both diseases (Figure 1F).Three key modules including 25 hub genes were identified (Figure 1G). The correlation analysis of immune cell infiltration showed the expression of B cells memory resting decreased and NK cells resting increased significantly in the two diseases (Figure 1H, I). Finally, estradiol in drug prediction outcomes has been shown to reduce susceptibility to COVID-19 and its severity through its involvement in regulating immune cells, while the most common manifestation of dry eye in pSS patients is strongly associated with low estrogen. Conclusion(s) High defense response to virus and response to interferon-alpha in pSS patients might be a crucial susceptible factor for COVID-19 and predictive drugs such as estradiol, suggested by susceptibility genes common to COVID-19 and pSS, may help in the clinical treatment of both diseases.