Identification of common functional pathways in patients with lupus and COVID-19 by time-series analysis

ABSTRACT

Background: Systemic lupus erythematosus (SLE) is a chronic autoimmune disorder characterized by abnormal activity of the immune system, producing the autoantibodies directed against nuclear and cytoplasmic antigens1. Infection is known as one of the common trigger factors for SLE. Coronavirus disease in 2019 (COVID-19), a severe acute respiratory syndrome, is now spreading rapidly throughout the world2.Though previous studies have addressed the susceptibility of lupus patients to the virus but how patients with SLE deal with COVID-19 is unclear up until now Objectives: To clarify the common pathogenesis of SLE and COVID-19, and find the appropriate treatment for Lupus and prevent COVID-19. Methods: The transcription profile of SLE (GSE38351) and COVID-19 (GSE161778) were obtained from the Gene Expression Omnibus database (GEO). R package was used to find differentially expressed genes (DEGs) between lupus patients and HCs. After background adjustment and other pre-procession, DEGs were extracted from the peripheral blood of patients with COVID-19 at three different disease progression(moderate, severe and remission status). The Short Time-series Expression Miner (STEM) was used to cluster and compare average DEGs with coherent changes. The different expression patterns of time-series genes (TSGs) were also compared among these patients. GO and KEGG pathway enrichment analysis of TSGs and DEGs were performed by Metascape. Results: Compared with HC, patients with SLE expressed 977 DEGs, which were mainly associated with defense response to virus, Epstein-Barr virus infection and response to interferon-γ(INF-γ) (Figure 1a). As for COVID-19 patients, there were 1584 DEGs obtained when compared with those of HCs (P < 0.05) (Figure 1b). Gene landscapes suggested the signatures of COVID-19 patients gradually changed during the disease progression, and gradually converge to HCs signatures. Time-series genes in the three stage of disease had different expression patterns and functions. A total of 959 TSGs in profile 3 showed a stable-stable-decreasing expression trend and significantly associated with INF signaling pathway (Figure 1c,1d). Interestingly, patients with SLE and COVID-19 shared common pathways such as INF-γ related functional pathway. Conclusion: INF-γ is an important common node of SLE and COVID-19. Controlling the production of INF-γ not only has therapeutic effect on SLE patients, but also may prevent COVID-19.