T cell-driven sustained inflammation and immune dysregulation mimicking immunosenescence for up to three years post-COVID-19
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Abstract
Long COVID has emerged as a major global health concern, yet the long-term trajectory of immune recovery and its contribution to persistent symptoms remain to be elucidated. Here, we conducted a three-year longitudinal follow-up of the 47 COVID-19 patients and applied single-cell RNA sequencing (scRNA-seq) and multiplex cytokine profiling to comprehensively characterize the peripheral immune landscape during convalescence.
We observed persistent immune dysregulation up to three years post-infection, characterized by chronic inflammation and impaired restoration of naïve CD4⁺ T cells, naïve CD8⁺ T cells, and SLC4A10⁺ MAIT cells—features reminiscent of immunosenescence.
Notably, Th17 cells, rather than monocytes, emerged as key drivers of chronic inflammation beyond one year. We identified two distinct Th17 subsets: RORC⁺ Th17 cells and LTB⁺ Th17 cells. While RORC⁺ Th17 cells were negatively correlated with inflammatory cytokine levels, LTB⁺ Th17 cells showed proinflammatory features and were positively associated with long COVID symptoms.
Sustained elevation of S100A8 and IL-16 in follow-up patients may contribute to the persistent presence of LTB⁺ Th17 cells.
Together, our study provides an in-depth longitudinal map of immune remodeling in COVID-19 convalescents, revealing key cellular and molecular drivers of sustained inflammation up to three years post-infection.
Web | DOI | PMC | PDF | Immunity & Inflammation | Open Access
Zheng, Tian; Gao, Ru; Liu, Yiwei; Wang, Yeming; Wu, Chao; Guo, Li; Chen, Lan; Wang, Xinming; Xiao, Yan; Zhong, Jingchuan; Zhang, Rongling; Wang, Ying; Ren, Xianwen; Cao, Bin; Ren, Lili; Wang, Jianwei
[Line breaks added]
Abstract
Long COVID has emerged as a major global health concern, yet the long-term trajectory of immune recovery and its contribution to persistent symptoms remain to be elucidated. Here, we conducted a three-year longitudinal follow-up of the 47 COVID-19 patients and applied single-cell RNA sequencing (scRNA-seq) and multiplex cytokine profiling to comprehensively characterize the peripheral immune landscape during convalescence.
We observed persistent immune dysregulation up to three years post-infection, characterized by chronic inflammation and impaired restoration of naïve CD4⁺ T cells, naïve CD8⁺ T cells, and SLC4A10⁺ MAIT cells—features reminiscent of immunosenescence.
Notably, Th17 cells, rather than monocytes, emerged as key drivers of chronic inflammation beyond one year. We identified two distinct Th17 subsets: RORC⁺ Th17 cells and LTB⁺ Th17 cells. While RORC⁺ Th17 cells were negatively correlated with inflammatory cytokine levels, LTB⁺ Th17 cells showed proinflammatory features and were positively associated with long COVID symptoms.
Sustained elevation of S100A8 and IL-16 in follow-up patients may contribute to the persistent presence of LTB⁺ Th17 cells.
Together, our study provides an in-depth longitudinal map of immune remodeling in COVID-19 convalescents, revealing key cellular and molecular drivers of sustained inflammation up to three years post-infection.
Web | DOI | PMC | PDF | Immunity & Inflammation | Open Access
