NINJ1 Defines a Hyperinflammatory Monocyte State Associated with Severe COVID-19.
4 affiliations
- 1Department of Rheumatology and Immunology, Xiangya Hospital, Department of Pathophysiology, Xiangya School of Basic Medicine Science, Central South University, Changsha 410000, China.
- 2Sepsis Translational Medicine Key Lab of Hunan Province, Changsha 410000, China.
- 3Postdoctoral Research Station of Biology, Xiangya School of Basic Medicine Science, Central South University, Changsha 410000, China.
- 4National Clinical Research Center for Geriatric Disorders, Xiangya Hospital, Central South University, Changsha 410000, China.
Abstract
Background/Objectives: Severe coronavirus disease 2019 (COVID-19) is characterized by dysregulated immune activation and excessive inflammation; however, the specific immune cell states that drive disease progression remain incompletely understood. Methods: Here, we integrated single-cell RNA sequencing analysis of peripheral blood mononuclear cells with clinical validation to investigate the role of Ninjurin-1 (NINJ1) in COVID-19-associated immune dysregulation. Results: Single-cell profiling revealed that NINJ1 expression was largely confined to monocytes and defined as a distinct NINJ1⁺ inflammatory monocyte state in patients with COVID-19. Compared with NINJ1⁻ monocytes, NINJ1⁺ monocytes exhibited enhanced inflammatory transcriptional programs, altered regulon activity, and increased cell-cell communication capacity, suggesting their potential role as a highly activated immune state involved in inflammatory amplification. Further ligand-receptor interaction analysis demonstrated that NINJ1⁺ monocytes functioned as key communication hubs within the COVID-19 immune landscape, coordinating extensive interactions with other immune populations. In an independent cohort of 99 COVID-19 patients and 51 healthy controls, serum NINJ1 levels were significantly elevated in infected individuals and were further increased in non-survivors. Circulating NINJ1 levels correlated with inflammatory and immune dysregulation indicators, including C-reactive protein, procalcitonin, prothrombin time, neutrophil-to-lymphocyte ratio, and lymphocyte depletion. Receiver operating characteristic analysis demonstrated that serum NINJ1 exhibited significant predictive value for in-hospital mortality. Conclusions: Collectively, our findings identify NINJ1⁺ inflammatory monocytes as an activated immune state associated with the transition from protective innate defense to pathological inflammation, providing new insights into COVID-19 immunopathogenesis and highlighting NINJ1 as a promising biomarker candidate for risk stratification and therapeutic exploration.
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BibTeX
@article{yu2026ninj1,
title = {{NINJ1 Defines a Hyperinflammatory Monocyte State Associated with Severe COVID-19.}},
author = {Fang Yu and Hao Ma and Muyuan Li and Huali Zhang and Yiying Yang},
journal = {Biomedicines},
year = {2026},
month = sep,
doi = {10.3390/biomedicines14102203},
url = {https://europepmc.org/article/MED/42940009},
note = {CC BY},
}
RIS
TY - JOUR
TI - NINJ1 Defines a Hyperinflammatory Monocyte State Associated with Severe COVID-19.
AU - Fang Yu
AU - Hao Ma
AU - Muyuan Li
AU - Huali Zhang
AU - Yiying Yang
PY - 2026
DA - 2026/09/29
JO - Biomedicines
DO - 10.3390/biomedicines14102203
UR - https://europepmc.org/article/MED/42940009
AB - Background/Objectives: Severe coronavirus disease 2019 (COVID-19) is characterized by dysregulated immune activation and excessive inflammation; however, the specific immune cell states that drive disease progression remain incompletely understood. Methods: Here, we integrated single-cell RNA sequencing analysis of peripheral blood mononuclear cells with clinical validation to investigate the role of Ninjurin-1 (NINJ1) in COVID-19-associated immune dysregulation. Results: Single-cell profiling revealed that NINJ1 expression was largely confined to monocytes and defined as a distinct NINJ1⁺ inflammatory monocyte state in patients with COVID-19. Compared with NINJ1⁻ monocytes, NINJ1⁺ monocytes exhibited enhanced inflammatory transcriptional programs, altered regulon activity, and increased cell-cell communication capacity, suggesting their potential role as a highly activated immune state involved in inflammatory amplification. Further ligand-receptor interaction analysis demonstrated that NINJ1⁺ monocytes functioned as key communication hubs within the COVID-19 immune landscape, coordinating extensive interactions with other immune populations. In an independent cohort of 99 COVID-19 patients and 51 healthy controls, serum NINJ1 levels were significantly elevated in infected individuals and were further increased in non-survivors. Circulating NINJ1 levels correlated with inflammatory and immune dysregulation indicators, including C-reactive protein, procalcitonin, prothrombin time, neutrophil-to-lymphocyte ratio, and lymphocyte depletion. Receiver operating characteristic analysis demonstrated that serum NINJ1 exhibited significant predictive value for in-hospital mortality. Conclusions: Collectively, our findings identify NINJ1⁺ inflammatory monocytes as an activated immune state associated with the transition from protective innate defense to pathological inflammation, providing new insights into COVID-19 immunopathogenesis and highlighting NINJ1 as a promising biomarker candidate for risk stratification and therapeutic exploration.
SN - 2227-9059
ER -