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

• Main Authors: Zekai Nian (Author), Yicheng Mao (Author), Zexia Xu (Author), Ming Deng (Author), Yixi Xu (Author), Hanlu Xu (Author), Ruoyao Chen (Author), Yiliu Xu (Author), Nan Huang (Author), Feiyang Mao (Author), Chenyu Xu (Author), Yulin Wang (Author), Mengyuan Niu (Author), Aqiong Chen (Author), Xiangyang Xue (Author), Huidi Zhang (Author), Gangqiang Guo (Author)
• Format: Book
• Published: BMC, 2024-06-01T00:00:00Z.
• Subjects: article
• Online Access: Connect to this object online.

Summary

Abstract Background 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. Methods 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. Results 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. Conclusions 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.

Item Description

10.1186/s10020-024-00851-6
1528-3658