Understanding the immunological basis for severe outcomes in COVID-19/Tuberculosis coinfection is critical. Our single-cell analysis identifies key drivers: profound lymphocyte loss through combined apoptosis and altered trafficking, excessive S100 protein-mediated inflammation contributing to cytokine storms, and systemic immune dysfunction characterized by exhausted T cells and suppressive myeloid populations. These findings pinpoint crucial nodes of immunopathology in severely coinfected individuals.
Abstract:
The immune characteristics and pathological mechanisms of COVID-19 and tuberculosis coinfection are not well understood. Single-cell RNA sequencing has emerged as a powerful tool for dissecting complex immune responses and cellular interactions in infectious diseases. Here, we employed scRNA-seq, combined with laboratory examinations and clinical observations, to elucidate potential mechanisms of immunopathology and protective immunity in coinfected patients. Substantial alterations in immune cell populations in patients with severe coinfection were observed, characterized by severe lymphopenia and massive expansion of myeloid cells. Lymphocytopenia may have resulted from lymphocyte apoptosis and migration. Systemic upregulation of S100 family proteins, mainly released by classical monocytes, might contribute to inflammatory cytokine storm via S100-TLR4–MyD88 signaling pathway in severely coinfected patients. Myeloid cells may contribute to immune paralysis in severe cases through expansion of myeloid-derived suppressor cells and dysregulated dendritic cell function. The immune landscape of T cells in severe patients were featured by dysregulated Th1 response, widespread exhaustion and increased cytotoxic, apoptosis, migration and inflammatory states. We observed increased plasma cells and overexpression of B-cell-activation-related pathways in severe patients. Together, we provide a comprehensive atlas illustrating the immune response to coinfected patients at the single-cell resolution and highlight mechanisms of pathogenesis in severe patients.
Author list:
Yi Wang*†, Maike Zheng†, Yun Zhang†, Yu Xue†, Sibo Long, Chaohong Wang, Qing Sun, Jun Yan, Yiheng Shi, Bin Yang, Shang Ma, Tiantian Zhang, Lei Cao, Yan Chen, Wenfu Ju, Jing Zhang, Yan Zhao, Mengqiu Gao, Laurence Don Wai Luu*, Xinting Yang*, Guirong Wang*
How to cite:
Y. Wang, M. Zheng, Y. Zhang, Y. Xue, S. Long, C. Wang, Q. Sun, J. Yan, Y. Shi, B. Yang, S. Ma, T. Zhang, L. Cao, Y. Chen, W. Ju, J. Zhang, Y. Zhao, M. Gao, L. D. W. Luu, X. Yang, G. Wang, Exploration 2025, 20240022.
https://doi.org/10.1002/EXP.20240022