Immune dysregulation in COVID-19 induced ARDS in kidney transplant recipients revealed by single-cell RNA sequencing.

Since the emergence of COVID-19 at the end of 2019, the disease has led to widespread acute respiratory distress syndrome (ARDS), particularly among kidney transplant recipients (KTRs), who are at increased risk due to long-term immunosuppressive therapy. This study aims to explore the differences in immune responses between kidney transplant recipients and non-kidney transplant recipients in COVID-19-induced ARDS to identify potential therapeutic targets for improving outcomes. Single-cell RNA sequencing was performed on 108,320 cells derived from peripheral blood samples to construct a global single-cell map of COVID-19 induced ARDS in kidney transplant recipients(ARDS), COVID-19 induced ARDS in non transplant recipients(ARDS), and healthy controls. Subsequently, using cellular clustering analysis, we obtained single-cell maps of different cell types. We employed enrichment analysis to determine the pathways involved in different subpopulations and focused on the role of key immune cells such as monocytes, megakaryocytes, B cells, and CD8 T cells in the pathogenesis of ARDS. Significant immune differences were observed between ARDS and ARDS. In ARDS, the S100A9 MK subpopulation, which activates the NF-κB signaling pathway, was elevated, promoting inflammation. In contrast, the S100A12 monocyte subpopulation that activates the chemokine signaling pathway was more abundant in ARDS, reflecting a stronger inflammatory response, while its abundance was reduced in ARDS due to immunosuppression. The CXCR4 B subpopulation, crucial for adaptive immunity, was significantly reduced in ARDS. Additionally, the XAF1 Teff subpopulation, associated with apoptosis, was more abundant in ARDS, potentially impairing immune recovery. This study highlights the immune differences between ARDS and ARDS, revealing the impact of immunosuppression on immune dysregulation. These findings suggest that targeting specific immune pathways can improve therapeutic strategies for ARDS.