Early Diagnosis of Sepsis: Current Status and Challenges

A special issue of Diagnostics (ISSN 2075-4418). This special issue belongs to the section "Clinical Laboratory Medicine".

Deadline for manuscript submissions: 30 June 2026 | Viewed by 1219

Special Issue Editors


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Guest Editor
Emergency Department, Fondazione Policlinico Universitario A. Gemelli, IRCSS, Rome, Italy
Interests: sepsis; biomarker discovery and validation; signaling pathways
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Guest Editor Assistant
Emergency Medicine, Università Cattolica del Sacro Cuore, Milan, Rome
Interests: emergency medicine

Special Issue Information

Dear Colleagues,

Sepsis is a widespread systemic disease and is a common reason for people to be admitted to the Emergency Department (ED). It is also one of the main causes of death among patients who access the ED.

According to the 2016 third international consensus on sepsis, sepsis is defined as a syndrome characterized by an uncontrolled response of the organism to an infectious stimulus, and it is considered a life-threatening condition. The incidence of sepsis has been steadily increasing since the first consensus definition (Sepsis-1) in 1991, with approximately 49 million cases of sepsis and 11 million sepsis-related deaths all over the world in 2017.

Based on existing literature, it is hypothesized that measuring presepsin levels in the ED could enhance the speed and specificity of diagnosis, compared to the current diagnostic approach, potentially improving outcomes for patients presenting with sepsis-like symptoms. The objective of our study is to evaluate the role of serum presepsin levels in the early diagnosis of sepsis in patients with suggestive clinical signs, comparing its performance with traditional biomarkers such as CRP, PCT, and blood cultures.

Septic shock is the most severe manifestation and should be defined as a subset of sepsis that presents particularly significant cellular, metabolic, and circulatory abnormalities. It is characterized by a drop in blood pressure, leading to reduced tissue perfusion pressure and causing characteristic shock-induced hypoxia. This condition results in an increase in mortality compared to sepsis alone.

Moreover, sepsis often presents a wide variety of symptoms that can resemble different medical conditions, highlighting the urgent need for more effective early diagnosis methods.

Over the years, scores (such as SOFA, qSOFA, SIRS, NEWS and MEWS), have been developed combining clinical and laboratory factors: for instance,sepsis is clinically identified as a response to infection that causes organ damage such as to increase the patient’s SOFA score by at least 2 points, compared to his baseline condition.

New tools need to improve early diagnosis of sepsis for example biomarkers can offer a rapid and straightforward approach to aid in the early detection of sepsis in emergency departments.

Dr. Andrea Piccioni
Guest Editor

Dr. Gloria Rozzi
Guest Editor Assistant

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Keywords

  • sepsis
  • early diagnosis of sepsis
  • biomarkers
  • sepsis mortality
  • serum presepsin
  • SOFA score

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Published Papers (1 paper)

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Review

21 pages, 337 KB  
Review
The Interleukin Network in Sepsis: From Cytokine Storm to Clinical Applications
by Marcello Candelli, Marta Sacco Fernandez, Gloria Rozzi, Giorgio Sodero, Andrea Piccioni, Giulia Pignataro, Donato Rigante and Francesco Franceschi
Diagnostics 2025, 15(22), 2927; https://doi.org/10.3390/diagnostics15222927 - 19 Nov 2025
Viewed by 887
Abstract
Background and Objectives: Despite major advances in medical science and critical care, sepsis remains a leading cause of morbidity and mortality worldwide: it arises from dysregulated host response to infections and may culminate in organ dysfunction. A hallmark of its pathogenesis is [...] Read more.
Background and Objectives: Despite major advances in medical science and critical care, sepsis remains a leading cause of morbidity and mortality worldwide: it arises from dysregulated host response to infections and may culminate in organ dysfunction. A hallmark of its pathogenesis is the cytokine storm, in which interleukins (ILs) serve as central mediators of both protective and deleterious immune responses. This review summarizes the current knowledge on the role of ILs in sepsis, emphasizing their potential as biomarkers and therapeutic targets. Material and Methods: We analyzed recent clinical and experimental studies focusing on the most studied ILs—including IL-1, IL-6, IL-10, IL-8, IL-12, IL-18, and IL-17—in the pathophysiology of sepsis. Attention was given to mechanistic insights, prognostic significance, and therapeutic strategies targeting IL pathways. Results: IL-1 and IL-6 emerged as key pro-inflammatory mediators, amplifying vascular permeability, coagulation activation, and shock, with IL-6 validated as a robust prognostic biomarker. IL-10 was identified as a pivotal anti-inflammatory cytokine, limiting tissue injury but fostering immunosuppression and secondary infections. Other ILs, such as IL-8, IL-12, IL-18, and IL-17, contributed to neutrophil recruitment, Th1/Th17 activation, organ-specific injury, and sepsis susceptibility. Therapeutic interventions targeting ILs, including the IL-1 receptor antagonist anakinra and IL-6 receptor blockade with tocilizumab, have shown promise in selected patient subgroups. Conclusions: ILs are central to the immunopathology of sepsis, acting both as drivers of hyperinflammation and mediators of immunosuppression. Their dual role underscores the relevance of ILs as diagnostic and prognostic biomarkers, as well as context-dependent therapeutic targets. Future approaches should prioritize precision immunomodulation aligned with the principles of personalized medicine to improve clinical outcomes in sepsis. Full article
(This article belongs to the Special Issue Early Diagnosis of Sepsis: Current Status and Challenges)
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