Acute Febrile Illness, Bacterial Infections, Sepsis, Viral Infections
Conditions
Brief summary
This study is a proteomics-based diagnostic biomarker study conducted on the same patient cohort as the transcriptomic biomarker study (NCT065529754). Although both studies share the same clinical cohort and overarching diagnostic aim, they are registered separately because they employ distinct omics technologies, investigate different biomarker modalities, and yield independent outcome measures.
Detailed description
This study aims to identify and validate proteomics-based diagnostic biomarkers for differentiating bacterial from viral acute febrile illnesses. It is conducted on the same patient cohort previously used in a registered transcriptomic biomarker study (ClinicalTrials.gov Identifier: NCT065529754). Although both studies share the overarching clinical objective of improving infection triage, they are scientifically independent in terms of methodology, biomarker modality, and analytical pipeline. Transcriptomic study (NCT065529754): Focused on host-response gene expression signatures derived from RNA sequencing data. Proteomic study (this registration): Focuses on host-response protein biomarkers identified through high-resolution mass spectrometry (DIA/PRM/SRM) and validated by immunoassays (ELISA). The proteomics study is designed to discover a minimal and biologically distinct set of protein markers that can be readily translated into clinical diagnostics. This study evaluates a minimal set of circulating proteins-ICAM1, CFHR5, and GRN-discovered through AI-assisted proteomics and validated by ELISA, as a rapid diagnostic tool for bacterial vs viral infection. Patients with acute fever are prospectively enrolled into three cohorts: discovery, internal validation, and external validation. This independent registration reflects the proteomics-specific objectives, methodology, and outcomes, while also acknowledging its linkage to the transcriptomics study.
Interventions
DIAGNOSTIC_TESTProteomic Biomarker Panel
A blood-based ELISA test measuring circulating ICAM1, CFHR5, and GRN. Index test performance will be evaluated against microbiological gold standards and adjudication.
Sponsors
Qilu Hospital of Shandong University
Study design
Observational model
COHORT
Time perspective
CROSS_SECTIONAL
Eligibility
Sex/Gender
ALL
Age
14 Years to No maximum
Healthy volunteers
No
Inclusion criteria
* Age ≥14 years； * Body temperature \> 38°C(within the past 72 hours)； * Disease duration ≤ 14 days； * Provision of informed consent by patient or legal guardian.
Exclusion criteria
* Underlying diseases affecting immune function (e.g., advanced malignancy, autoimmune disease, immunodeficiency, use of immunosuppressants); * Pregnancy; * Mixed infections (including viral-bacterial co-infections, bacterial or viral-fungal co-infections, or autoimmune disease concomitant with bacterial infection); * indeterminate or negative microbiological testing ; * inability to provide informed consent
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Diagnostic Accuracy (AUROC) for differentiating bacterial vs viral infection | At hospital admission (retrospective review of cases from September 1, 2021 to October 31, 2024) | The area under the receiver operating characteristic curve (AUROC) will be calculated for the selected host-response protein biomarker panel to assess its ability to discriminate bacterial from viral infections in patients presenting with acute febrile illness. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Incremental diagnostic value of biomarker panel combined with CRP | At hospital admission (retrospective review of cases from September 1, 2021 to October 31, 2024) | Evaluate the increase in area under the receiver operating characteristic curve (AUROC) when the host-response protein biomarker panel is combined with CRP for distinguishing bacterial from viral infections. |
| Prognostic value for sepsis severity (qSOFA ≥2) and adverse outcomes | At hospital admission (retrospective review of cases from September 1, 2021 to November 30, 2024) | Assess the ability of the biomarker panel to predict clinical disease severity in patients with acute febrile illness, as measured by the qSOFA score. |
| Sensitivity, specificity, PPV, NPV, LR+/LR- for differentiating bacterial vs viral infection | At hospital admission (retrospective review of cases from September 1, 2021 to October 31, 2024) | — |
Countries
China
Outcome results
None listed