tetano
Editor, Senior Moderator
Front Immunol
. 2025 Apr 30:16:1577803.
doi: 10.3389/fimmu.2025.1577803. eCollection 2025. The CD38[SUP]+[/SUP]HLA-DR[SUP]+[/SUP] T cells with activation and exhaustion characteristics as predictors of severity and mortality in COVID-19 patients
Qiuyue Long[SUP] #[/SUP][SUP] 1 2 [/SUP], Shixu Song[SUP] #[/SUP][SUP] 1 2 [/SUP], Jianbo Xue[SUP] #[/SUP][SUP] 3 [/SUP], Wenyi Yu[SUP] 3 [/SUP], Yaolin Zheng[SUP] 1 2 [/SUP], Jiwei Li[SUP] 4 [/SUP], Jing Wu[SUP] 1 2 [/SUP], Xiaoyi Hu[SUP] 2 3 [/SUP], Mingzheng Jiang[SUP] 1 2 [/SUP], Hongli Ye[SUP] 1 2 [/SUP], Binghan Zheng[SUP] 1 2 [/SUP], Minghui Wang[SUP] 1 2 [/SUP], Fangfang Wu[SUP] 1 2 [/SUP], Ke Li[SUP] 5 [/SUP], Zhancheng Gao[SUP] 1 2 3 [/SUP], Yali Zheng[SUP] 1 2 6 [/SUP]
Affiliations
Background: The COVID-19 pandemic remains a global health challenge. Severe cases often respond poorly to standard treatments, highlighting the necessity for novel therapeutic targets and early predictive biomarkers.
Methods: We utilized flow cytometry to analyze peripheral immune cells from healthy, bacterial pneumonia patients, and COVID-19 patients. The expansion of activated T cells (CD38[SUP]+[/SUP]HLA-DR[SUP]+[/SUP]), monocytes, and myeloid-derived suppressor cells (MDSCs) were detected and correlated with clinical outcomes to evaluate prognostic potential. The single-cell RNA sequencing (scRNA-seq) was applied to characterize the critical cell subset associated with prognosis and elucidate its phenotype in COVID-19.
Results: We revealed a significant increase in CD38[SUP]+[/SUP]HLA-DR[SUP]+[/SUP] T cells in non-survivor COVID-19 patients, establishing them as an independent risk factor for 28-day mortality. The scRNA-seq analysis identified the CD38[SUP]+[/SUP]HLA-DR[SUP]+[/SUP] T cell as a terminally differentiated, Treg-like subset exhibiting both activation and exhaustion characteristics. This subset presented the highest IL-6 and IL-10 mRNA levels among all T-cell subsets. Further functional analysis demonstrated its enhanced major histocompatibility complex class II (MHC-II) cross-signaling and correspondingly enriched cytoskeletal rearrangement processes. In addition, there was dysregulated NAD[SUP]+[/SUP] metabolism in CD38+HLA-DR+ T cells via scRNA-seq, accompanied by elevated adenosine and decreased NAD[SUP]+[/SUP] levels in serums from COVID-19 patients.
Conclusions: We identified the selective expansion of CD38[SUP]+[/SUP]HLA-DR[SUP]+[/SUP] T cells as a novel prognostic indicator for COVID-19 outcomes. These cells' unique activated-exhausted phenotype, along with their impact on NAD[SUP]+[/SUP] metabolism, provides new insights into COVID-19 immunopathogenesis.
Keywords: CD38+HLA-DR+ T cells; COVID-19; T cells; mortality risk factor; single-cell transcriptomics.
. 2025 Apr 30:16:1577803.
doi: 10.3389/fimmu.2025.1577803. eCollection 2025. The CD38[SUP]+[/SUP]HLA-DR[SUP]+[/SUP] T cells with activation and exhaustion characteristics as predictors of severity and mortality in COVID-19 patients
Qiuyue Long[SUP] #[/SUP][SUP] 1 2 [/SUP], Shixu Song[SUP] #[/SUP][SUP] 1 2 [/SUP], Jianbo Xue[SUP] #[/SUP][SUP] 3 [/SUP], Wenyi Yu[SUP] 3 [/SUP], Yaolin Zheng[SUP] 1 2 [/SUP], Jiwei Li[SUP] 4 [/SUP], Jing Wu[SUP] 1 2 [/SUP], Xiaoyi Hu[SUP] 2 3 [/SUP], Mingzheng Jiang[SUP] 1 2 [/SUP], Hongli Ye[SUP] 1 2 [/SUP], Binghan Zheng[SUP] 1 2 [/SUP], Minghui Wang[SUP] 1 2 [/SUP], Fangfang Wu[SUP] 1 2 [/SUP], Ke Li[SUP] 5 [/SUP], Zhancheng Gao[SUP] 1 2 3 [/SUP], Yali Zheng[SUP] 1 2 6 [/SUP]
Affiliations
- PMID: 40370439
- PMCID: PMC12074963
- DOI: 10.3389/fimmu.2025.1577803
Background: The COVID-19 pandemic remains a global health challenge. Severe cases often respond poorly to standard treatments, highlighting the necessity for novel therapeutic targets and early predictive biomarkers.
Methods: We utilized flow cytometry to analyze peripheral immune cells from healthy, bacterial pneumonia patients, and COVID-19 patients. The expansion of activated T cells (CD38[SUP]+[/SUP]HLA-DR[SUP]+[/SUP]), monocytes, and myeloid-derived suppressor cells (MDSCs) were detected and correlated with clinical outcomes to evaluate prognostic potential. The single-cell RNA sequencing (scRNA-seq) was applied to characterize the critical cell subset associated with prognosis and elucidate its phenotype in COVID-19.
Results: We revealed a significant increase in CD38[SUP]+[/SUP]HLA-DR[SUP]+[/SUP] T cells in non-survivor COVID-19 patients, establishing them as an independent risk factor for 28-day mortality. The scRNA-seq analysis identified the CD38[SUP]+[/SUP]HLA-DR[SUP]+[/SUP] T cell as a terminally differentiated, Treg-like subset exhibiting both activation and exhaustion characteristics. This subset presented the highest IL-6 and IL-10 mRNA levels among all T-cell subsets. Further functional analysis demonstrated its enhanced major histocompatibility complex class II (MHC-II) cross-signaling and correspondingly enriched cytoskeletal rearrangement processes. In addition, there was dysregulated NAD[SUP]+[/SUP] metabolism in CD38+HLA-DR+ T cells via scRNA-seq, accompanied by elevated adenosine and decreased NAD[SUP]+[/SUP] levels in serums from COVID-19 patients.
Conclusions: We identified the selective expansion of CD38[SUP]+[/SUP]HLA-DR[SUP]+[/SUP] T cells as a novel prognostic indicator for COVID-19 outcomes. These cells' unique activated-exhausted phenotype, along with their impact on NAD[SUP]+[/SUP] metabolism, provides new insights into COVID-19 immunopathogenesis.
Keywords: CD38+HLA-DR+ T cells; COVID-19; T cells; mortality risk factor; single-cell transcriptomics.