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Peer-reviewedCC BY 4.0Frontiers in Immunology

Early warning indicators for severe hemorrhagic fever with renal syndrome

  • Xiaojiao Li1,2,3
  • Lin Su2,3
  • Yinli He2,3
  • Linpei Zhang2,3
  • Tianyan Chen1
  • Minhong Fei4
  • Yawen Wang2,3,5
5 affiliations
  1. 1Infectious Diseases Department, The First Affiliated Hospital of Xi’an Jiaotong University
  2. 2BioBank, The First Affiliated Hospital of Xi’an Jiaotong University
  3. 3Shaanxi Engineering Research Center for Biobank and Advanced Medical Research, The First Affiliated Hospital of Xi’an Jiaotong University
  4. 4Jiangyan Hospital of Traditional Chinese Medicine
  5. 5Department of Laboratory Medicine, First Affiliated Hospital, School of Medicine, Xi’an Jiaotong University
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Abstract

Hemorrhagic fever with renal syndrome (HFRS) remains a significant public health concern, and early identification of severe cases is critical for improving outcomes. This review synthesizes recent advances in early warning indicators for severe HFRS. Clinically accessible indicators form the basis of early risk stratification. Key bedside signs such as high fever, severe gastrointestinal symptoms, altered mental status, and overt bleeding tendency, together with routine laboratory parameters including thrombocytopenia, leukocytosis, and elevated procalcitonin, have consistently shown robust predictive value for disease severity and mortality. Immunological markers provide mechanistic insight that also supports early identification of severe HFRS, as reflected by a core cytokine imbalance, impaired antigen-specific T- and B-cell responses, and aberrant activation of monocytes, neutrophils, and the complement system. Emerging biomarkers of endothelial barrier disruption, early renal tubular injury, oxidative stress, and metabolic dysregulation may further enhance predictive capacity. Despite these advances, challenges remain regarding external validation and clinical translation. Future research should focus on establishing standardized, multicenter-validated early warning systems to enable precise management of severe HFRS.

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Cite

BibTeXRIS
BibTeX
@article{li2026early,
  title = {{Early warning indicators for severe hemorrhagic fever with renal syndrome}},
  author = {Xiaojiao Li and Lin Su and Yinli He and Linpei Zhang and Tianyan Chen and Minhong Fei and Yawen Wang},
  journal = {Frontiers in Immunology},
  year = {2026},
  month = oct,
  doi = {10.3389/fimmu.2026.1986264},
  url = {https://www.frontiersin.org/articles/10.3389/fimmu.2026.1986264/full},
  note = {CC BY 4.0},
}
RIS
TY  - JOUR
TI  - Early warning indicators for severe hemorrhagic fever with renal syndrome
AU  - Xiaojiao Li
AU  - Lin Su
AU  - Yinli He
AU  - Linpei Zhang
AU  - Tianyan Chen
AU  - Minhong Fei
AU  - Yawen Wang
PY  - 2026
DA  - 2026/10/26
JO  - Frontiers in Immunology
DO  - 10.3389/fimmu.2026.1986264
UR  - https://www.frontiersin.org/articles/10.3389/fimmu.2026.1986264/full
AB  - Hemorrhagic fever with renal syndrome (HFRS) remains a significant public health concern, and early identification of severe cases is critical for improving outcomes. This review synthesizes recent advances in early warning indicators for severe HFRS. Clinically accessible indicators form the basis of early risk stratification. Key bedside signs such as high fever, severe gastrointestinal symptoms, altered mental status, and overt bleeding tendency, together with routine laboratory parameters including thrombocytopenia, leukocytosis, and elevated procalcitonin, have consistently shown robust predictive value for disease severity and mortality. Immunological markers provide mechanistic insight that also supports early identification of severe HFRS, as reflected by a core cytokine imbalance, impaired antigen-specific T- and B-cell responses, and aberrant activation of monocytes, neutrophils, and the complement system. Emerging biomarkers of endothelial barrier disruption, early renal tubular injury, oxidative stress, and metabolic dysregulation may further enhance predictive capacity. Despite these advances, challenges remain regarding external validation and clinical translation. Future research should focus on establishing standardized, multicenter-validated early warning systems to enable precise management of severe HFRS.
SN  - 1664-3224
ER  -