Multi-omics analysis uncovered systemic lupus erythematosus and COVID-19 crosstalk

• Published in: Molecular medicine (Cambridge, Mass.) Mass.), 2024-06, Vol.30 (1), p.81-23
• Main Authors: Nian, Zekai, Mao, Yicheng, Xu, Zexia, Deng, Ming, Xu, Yixi, Xu, Hanlu, Chen, Ruoyao, Xu, Yiliu, Huang, Nan, Mao, Feiyang, Xu, Chenyu, Wang, Yulin, Niu, Mengyuan, Chen, Aqiong, Xue, Xiangyang, Zhang, Huidi, Guo, Gangqiang
• Format: Article
• Language: English
• Subjects: COVID-19; COVID-19 - genetics; Cytokine release syndrome; Female; Gene Expression Profiling; Genome-Wide Association Study; Humans; Interferon; JAK-STAT; Janus Kinases - metabolism; Lupus Erythematosus, Systemic - genetics; Male; Monokine; Multiomics; SARS-CoV-2 - physiology; Signal Transduction; STAT Transcription Factors - genetics; STAT Transcription Factors - metabolism; Systemic lupus erythematosus; Transcriptome
• ISSN: 1528-3658; 1076-1551; 1528-3658
• DOI: 10.1186/s10020-024-00851-6

Studies have highlighted a possible crosstalk between the pathogeneses of COVID-19 and systemic lupus erythematosus (SLE); however, the interactive mechanisms remain unclear. We aimed to elucidate the impact of COVID-19 on SLE using clinical information and the underlying mechanisms of both diseases. RNA-seq datasets were used to identify shared hub gene signatures between COVID-19 and SLE, while genome-wide association study datasets were used to delineate the interaction mechanisms of the key signaling pathways. Finally, single-cell RNA-seq datasets were used to determine the primary target cells expressing the shared hub genes and key signaling pathways. COVID-19 may affect patients with SLE through hematologic involvement and exacerbated inflammatory responses. We identified 14 shared hub genes between COVID-19 and SLE that were significantly associated with interferon (IFN)-I/II. We also screened and obtained four core transcription factors related to these hub genes, confirming the regulatory role of the IFN-I/II-mediated Janus kinase/signal transducers and activators of transcription (JAK-STAT) signaling pathway on these hub genes. Further, SLE and COVID-19 can interact via IFN-I/II and IFN-I/II receptors, promoting the levels of monokines, including interleukin (IL)-6/10, tumor necrosis factor-α, and IFN-γ, and elevating the incidence rate and risk of cytokine release syndrome. Therefore, in SLE and COVID-19, both hub genes and core TFs are enriched within monocytes/macrophages. The interaction between SLE and COVID-19 promotes the activation of the IFN-I/II-triggered JAK-STAT signaling pathway in monocytes/macrophages. These findings provide a new direction and rationale for diagnosing and treating patients with SLE-COVID-19 comorbidity.