MicroRNAs in sepsis: Advances in diagnosis and prognostic monitoring

Abstract

Sepsis and septic shock remain major global health challenges, with persistently high mortality despite advances in critical care. Conventional diagnostic tools, including the Sequential Organ Failure Assessment score and biomarkers such as C-reactive protein and procalcitonin, lack sufficient sensitivity and specificity, particularly in early disease. Circulating microRNAs (miRNAs), small non-coding RNAs regulating gene expression, have emerged as promising biomarkers for early diagnosis, prognostic assessment, and therapeutic monitoring. This narrative review synthesizes clinical studies published after 2022, highlighting the evolving role of circulating and extracellular vesicle-derived miRNAs in sepsis. Diagnostic investigations confirmed the accuracy of miRNA-451a (miR-451a) and miR-9-5p, while expanding evidence supports miR-193b-5p and miR-135a as additional diagnostic candidates. Contrasting results on miR-181a-5p emphasize the need for further validation. Prognostic and therapeutic monitoring studies identified miR-155, miR-182, miR-146b-5p, miR-126-5p, miR-195, and miR-497 as dynamic markers reflecting immune modulation and disease trajectory. Collectively, these findings highlight circulating miRNAs as powerful, versatile biomarkers that advance precision medicine in sepsis, pending multicenter validation and methodological standardization for clinical translation.

Key Words: Sepsis; Septic shock; Circulating microRNAs; Biomarkers; Diagnosis; Prognosis; Extracellular vesicles; Precision medicine

Core Tip: Circulating microRNAs (miRNAs) are emerging as stable and specific biomarkers for sepsis and septic shock diagnosis, prognosis, and therapeutic monitoring. Recent studies validate miRNA-451a (miR-451a), miR-9-5p, miR-193b-5p, miR-135a, miR-155, and miR-182 as superior to conventional markers, reflecting disease severity and immune status. Future diagnostic strategies may benefit from combination miRNA panels, which could enhance accuracy and support precision medicine in sepsis care. Large multicenter studies and methodological standardization remain essential to ensure reproducibility and enable their integration into clinical practice.

INTRODUCTION

Sepsis is defined as a life-threatening organ dysfunction, while septic shock refers to a subset characterized by profound circulatory and metabolic abnormalities, associated with mortality rates exceeding 40% despite optimal care[1]. Globally, sepsis affects approximately 49 million individuals annually and accounts for 11 million deaths, representing nearly 20% of total mortality[2].

Prompt and accurate diagnosis of sepsis is advocated by international guidelines, including the Surviving Sepsis Campaign, which recommends initiating diagnostic and therapeutic measures within the first hour of recognition[3]. The current diagnostic framework is based on the sepsis-3 criteria, which utilize tools such as the Sequential Organ Failure Assessment (SOFA) score; however, this clinical score has limited sensitivity and specificity in the early phases of sepsis[1]. Diagnostic accuracy is further challenged by the heterogeneity of the condition, encompassing a wide range of pathogens, immune responses, and patient comorbidities[4].

Laboratory testing, including conventional biomarkers and emerging tools such as microRNAs (miRNAs), can contribute to shorten time to diagnosis and improve diagnostic accuracy in sepsis[5]. Conventional biomarkers employed for diagnosis and therapeutic monitoring in sepsis, including lactate clearance, C-reactive protein, (CRP) and procalcitonin (PCT) are reported having limited specificity in general, marking a need for new diagnostic strategies[6,7]. Recent advances in molecular profiling have identified novel regulatory pathways and potential biomarkers involved in the host response to sepsis. For example, a recent case-control investigation[8] reported that the chemokine CXC motif chemokine ligand 5 may serve as a promising candidate for improving both diagnostic accuracy and prognostic assessment in septic patients. In parallel, an integrated bioinformatic and experimental analysis[9] identified the long non-coding RNA LINC02363 as a potential biomarker for the early detection and prognostic stratification of sepsis, given its significant upregulation in affected individuals compared with healthy controls. however, more in-depth functional studies are needed to validate their application in the clinical setting. The miRNAs are small non-coding RNAs (18-25 nucleotides), detectable in blood stream, that regulate gene expression post-transcriptionally and exhibit greater stability than most protein-based or mRNA biomarkers, as they are protected within exosomes or bound to protein complexes[10]. Recent reviews have highlighted how some miRNAs fragments, such as miRNA-146a (miR-146a), miR-223, and miR-155-5p, have diagnostic and prognostic utility in sepsis, offering enhanced specificity and sensitivity over traditional biomarkers[11,12]. These molecules may enable biomarker-guided therapeutic strategies and improve the precision of intensive care interventions.

Thereafter, several clinical studies have expanded evidence related to the role of miRNA fragments detectable in blood stream as biomarkers of sepsis diagnosis and now provide insights related to prognostication and efficacy of therapeutic management.

Aim of this review is to report the latest clinical evidence, after 2022, related to the role of miRNAs in diagnosis, prognostication and therapeutic monitoring of sepsis and septic shock.

THE MIRNA FRAGMENTS IN THE DIAGNOSIS OF SEPSIS AND SEPTIC SHOCK

Evidence extracted from clinical studies published after 2022 report insights that confirm (miR-451a, miR-9-5p), expand (miR-193b-5p, miR-135a) and challenge (miR-181a-5p) the earlier findings about miRNA in the diagnosis of sepsis and septic shock (Table 1)[13-17].

Table 1 Summary of studies on the diagnostic role of microRNAs in sepsis and septic shock.

Ref.	Year	Study type	Up/downregulated	Area under the curve	MicroRNAs	Diagnostic purpose	Sample size
García-Concejo et al[14]	2025	Prospective multicenter observational study	Down	0.960 (validation)	MiR-451a, miR-100-5p, miR-148a-3p	Differentiating septic shock from non-septic shock	161 (109 discovery, 52 validation)
Ye et al[15]	2025	Prospective observational cohort study	Up	0.825 (sepsis), 0.821 (septic shock)	MiR-9-5p	Predicting sepsis and septic shock	134 (69 sepsis, 30 non-sepsis, 35 healthy)
Li et al[13]	2025	Prospective observational study	Down	13.17	MiR-193b-5p	Distinguishing sepsis from healthy conditions	105 (15 exploratory, 90 validation)
Behroozizad et al[16]	2024	Case-control study	Up	1.25	MiR-135a	Independent predictor of sepsis	200 (100 sepsis, 100 healthy)
Li et al[17]	2025	Case-control study	Up	14.39	MiR-181a-5p	Biomarker for sepsis	244 (119 sepsis, 125 healthy)

MiR: MiRNA.

Two studies confirmed the relevant role of miR-451a and of miR-9-5p, both of which were already studied in literature[11-13,18], in differentiating septic shock from non-septic shock in postsurgical patients[14,15]. Regarding miR-451a, a prospective multicentre observational study, that enrolled a discovery cohort with 109 patients and a validation cohort with 52 patients, has identified a combination of miR-451a, miR-100-5p and miR-148a-3p with strong diagnostic capabilities[14]. These three miRNAs were significantly downregulated in septic shock patients compared to those with non-septic shock. The combined diagnostic accuracy of this three-miRNA panel was remarkably high, achieving an area under the curve (AUC) of 0.894 in the discovery cohort and validating at 0.960 with qPCR in a separate cohort. When combined with PCT, the AUC further improved to 0.976. This miRNA-based model also outperformed CRP and PCT alone in diagnostic accuracy. The value of miR-9-5p, a miRNA already listed in the top 10 upregulated differentially expressed miRNAs in patients with sepsis and septic shock[13], has been confirmed in a single-center, prospective, observational cohort study involving 69 sepsis patients, 30 non-sepsis patients, and 35 healthy controls[15]. These findings revealed a significant upregulation of miR-9-5p in sepsis patients compared to both non-sepsis infected patients and healthy controls. For diagnosis, miR-9-5p demonstrated an AUC of 0.825 for predicting sepsis and 0.821 for septic shock. Similarly to the signature of miR-100-5p, miR-148a-3p and miR-451a, miR-9-5p alone surpassed the diagnostic accuracy of CRP and PCT for sepsis.

Two studies expanded the understanding of the diagnostic and prognostic role of miR-193b-5p and miR-135a, already investigated in pre-clinical studies[19,20], in the context of sepsis and septic shock[13,16]. A prospective observational study first conducted exosomal miRNA sequencing on serum samples from a small exploratory cohort (6 sepsis patients, 6 septic shock patients, and 3 healthy controls), identifying miR-193b-5p and miR-511-5p as immune-related candidates[13]. This was followed by a larger validation cohort involving 90 participants (30 sepsis patients, 30 septic shock patients, and 30 general surgery controls), with miRNA levels quantified via quantitative real-time polymerase chain reaction. The results showed that miR-193b-5p was significantly downregulated in both sepsis and septic shock patients compared to healthy controls. In distinguishing sepsis from healthy conditions, miR-193b-5p achieved an AUC of 0.797, with an optimal cut-off value of 2.08, yielding a sensitivity of 85.0% and a specificity of 73.3%. A 2024 case-control study evaluated the diagnostic and prognostic value of circulating miR-135a and miR-193b in a larger population of 200 individuals, including 100 sepsis patients admitted to intensive care units and 100 healthy controls[16]. Plasma miRNA levels were measured using qPCR. The expression of miR-135a was found to be significantly elevated in septic patients (P < 0.0001). The receiver operating characteristic (ROC) curve analysis demonstrated good diagnostic power, with an AUC of 0.85, sensitivity of 74%, and specificity of 89%. Multivariate logistic regression analysis confirmed miR-135a as an independent predictor of sepsis (odds ratio = 0.16), supporting its clinical relevance as a diagnostic biomarker.

One study challenged the previously reported role of miR-181a-5p as a downregulated miRNA in sepsis[17]. While earlier review had described miR-181a-5p as being consistently downregulated in septic patients[21], a case-control study published in 2025 provided contrasting findings, revealing a significant upregulation of this miRNA in the serum of sepsis patients. This study included a total of 244 participants, with 119 sepsis patients and 125 healthy controls and serum miR-181a-5p levels were quantified using quantitative real-time polymerase chain reaction. In contrast to previous reports, miR-181a-5p expression was significantly elevated in sepsis patients compared to controls (P < 0.001). Diagnostic performance assessed through ROC curve analysis showed an AUC of 0.879, with a sensitivity of 73.1% and a specificity of 89.6%, suggesting that miR-181a-5p may serve as a valuable biomarker for sepsis despite earlier evidence to the contrary.

In summary, recent clinical studies confirmed the diagnostic role of miR-451a as part of a three-miRNA panel that outperformed CRP and PCT[14] and of miR-9-5p, which reliably distinguished sepsis and septic shock[15]. The miR-193b-5p was shown to be downregulated with good diagnostic accuracy[13], while miR-135a emerged as an independent predictor in ICU patients[16]. Conversely, miR-181a-5p was found upregulated[17], challenging prior evidence of downregulation[21] but still demonstrating diagnostic value. Together, these findings support the profiling of circulating miRNAs fragments as promising tools for improving diagnostic accuracy in sepsis and septic shock.

THE MIRNA FRAGMENTS IN PROGNOSIS AND THERAPEUTIC MONITORING OF SEPSIS AND SEPTIC SHOCK

Insights from clinical studies published after 2022 confirm (miR-155) and expand upon (miR-182, miR-195, miR-497, miR-126-5p), and challenge (miR-146b-5p) previous findings regarding the role of miRNAs in the prognosis, therapeutic guidance, and monitoring of treatment efficacy for sepsis and septic shock (Table 2)[22-27].

Table 2 Summary of studies on the prognostic and therapeutic monitoring role of microRNAs in sepsis and septic shock.

Ref.	Year	Study type	Up/downregulated	AUC/HR/OR	MicroRNAs	Prognostic/therapeutic purpose	Sample size
Wang et al[22]	2024	Retrospective clinical study	Down (post-treatment)	Not specified	MiR-155, miR-146a	Monitoring treatment efficacy (ulinastatin + HBPT)	150 (77 HBPT + ulinastatin, 73 HBPT)
Fan et al[23]	2024	Prospective cohort study	Up (in SAKI)	OR = 1.21	MiR-155	Prognosis of SAKI and 28-day mortality	150 (79 SAKI, 71 septic non-acute kidney injury)
Zhang et al[24]	2025	Prospective cohort study	Up (lower levels = better survival)	AUC = 0.735	MiR-182	Predicting 28-day mortality	178 (128 sepsis, 50 healthy)
Liu et al[25]	2024	Longitudinal study	Fluctuates	AUC = 0.72 (for miR-497)	MiR-195, MiR-497	Guiding timing of immunotherapy/predicting mortality	10 (120 collected samples)
Cheng et al[26]	2025	Prospective single-center cohort study	Down (reduced levels = poor prognosis)	HR = 3.063, AUC = 0.691	MiR-146b-5p	Independent predictor of 28-day mortality	191 septic patients
Mao et al[27]	2023	Observational clinical study	Down (in ALI)	AUC = 0.777	MiR-126-5p	Prognostic factor for sepsis-induced ALI	240 (120 sepsis, 120 healthy)

ALI: Acute lung injury; AUC: Area under the curve; HBPT: Hybrid blood purification treatment; HR: Hazard ratio; MiR: MiRNA; OR: Odds ratio; SAKI: Sepsis-associated acute kidney injury.

Two recent studies[22,28] highlight the critical role of miR-155 as a biomarker for assessing patient prognosis and disease severity in the context of sepsis and its complications. A retrospective study[22] confirmed the prognostic role of miR-155 in sepsis, as its down-regulation is significantly associated with patient survival[28]. This retrospective clinical study was conducted on a sample of 150 patients with severe sepsis to demonstrate the role of miR-155 as a biomarker to verify treatment efficacy. The main objective of the study was to investigate the effect of combining ulinastatin with hybrid blood purification treatment (HBPT) on the APACHE II score, levels of miR-146a and miR-155, and other clinical outcomes in patients with severe sepsis. Post-treatment levels of both miR-146a and miR-155 were significantly lower in the combination therapy group compared to the HBPT-only group (miR-146a: 3.22 vs 5.18, P < 0.001; miR-155: 1.09 vs 1.36, P < 0.001). The HBPT + ulinastatin group showed significantly lower levels of CRP, tumor necrosis factor-alpha, and PCT compared to the HBPT group (all P < 0.001). The combination therapy group demonstrated significantly shorter recovery times and length of hospital stay (all P < 0.001). Another recent study[23] confirmed the role of miR-155 in sepsis-associated acute kidney injury (SAKI). This prospective cohort study was conducted on 150 patients with sepsis, divided into a SAKI group (n = 79) and a septic non-acute kidney injury group (n = 71). The main objective was to evaluate the clinical role of serum miR-155 for the early diagnosis and prognosis of SAKI. The clinical results showed that the expression of miR-155 was significantly higher in the SAKI group compared to the non- acute kidney injury group (P < 0.001) and increased as kidney damage worsened (P = 0.001). For prognostic purposes, a multivariate analysis identified miR-155 (OR = 1.21, P = 0.001), the severity of kidney injury (P < 0.001), and the APACHE II score (P < 0.001) as independent risk factors for 28-day mortality.

A pre-clinical study[24] significantly expanded the understanding of miR-182's role in sepsis, building upon its initial identification in a pre-clinical rat model[29] which implicated miR-182 in the septic response, observing that its expression was altered in the liver of septic rats and restored by treatment with activated protein C. The more recent investigation consists in a prospective study on a cohort of 178 individuals, comprising 128 sepsis patients (46 with sepsis and 82 with septic shock) and 50 healthy controls, with the primary objective of evaluating the prognostic value of circulating miR-182. The main clinical findings showed that plasma miR-182 levels were markedly elevated in sepsis patients compared to controls, with a further significant increase in patients with septic shock. Additionally, miR-182 concentrations positively correlated with established severity scores, including the APACHE II score (r = 0.206, P = 0.019) and the SOFA score (r = 0.1747, P = 0.0485). Crucially, miR-182 demonstrated strong prognostic power for predicting 28-day mortality, with an AUC of 0.735, a sensitivity of 81.5%, and a specificity of 71.3%. Kaplan-Meier analysis confirmed that patients with lower miR-182 levels had significantly improved survival.

A longitudinal study[25] expands the evidence of the role of miR-195 already investigated in a preclinical study[30] and of miR-497 in induced-sepsis myocardial injury in children[31]. The longitudinal study was conducted on a sample of 10 sepsis patients with the primary objective of investigating the dynamic expression of small extracellular vesicle miRNAs to potentially guide the timing of immunotherapy. The main clinical findings revealed that levels of MIR497HG, miR-195, and miR-497 fluctuate in a periodic 4-5 days cycle, corresponding with the patients' shifting immune status. The levels of small extracellular vesicle MIR497HG and miR-195 were also shown to correlate with the SOFA score. For predicting 28-day mortality, miR-497 demonstrated the highest accuracy with an AUC of 0.72. Monitoring these cyclical changes could help determine a patient's real-time immune state (immunoactivation or immunosuppression) to optimize the timing of personalized therapy.

A prospective study[26] challenged the findings on miR-146b-5p of a previous pre-clinical study[32]. While the pre-clinical study in a rat model of sepsis identified the upregulation of miR-146b-5p as a pathogenic driver of intestinal injury, this prospective, single-center cohort study in 191 human septic patients (117 nonsurvivors and 74 survivors) demonstrated the exact opposite: Reduced circulating levels of miR-146b-5p are independently associated with a poor prognosis. This clinical investigation assessed the dynamic variation of miR-146b-5p in septic and non-septic patients compared with healthy controls. Levels were significantly reduced in septic patients during the first 12 days (all P < 0.0001) but showed a gradual recovery over time. By the third week, values were no longer significantly different from those of controls (P = 0.2763). This recovery was observed only in survivors: Non-survivors maintained persistently lower levels than survivors at all time points. Patients with miR-146b-5p ≤ 0.272 had a nearly threefold higher risk of death (hazard ratio = 3.063), and Kaplan–Meier curves showed significantly reduced survival in this group (log-rank χ² = 39.46, P < 0.001). Multivariate Cox regression validated miR-146b-5p as an independent predictor of 28-day mortality (hazard ratio = 0.145, 95%CI: 0.044-0.476, P = 0.001), while logistic regression confirmed its prognostic role (P = 0.02). The levels of miR-146b-5p showed an inverse correlation with APACHE II scores, and ROC analysis confirmed their complementarity, with the miRNA alone yielding an AUC of 0.691 and the combination with APACHE II achieving the highest predictive accuracy (AUC = 0.785).

A recent clinical study[27] expands on previous preclinical findings[33], suggesting that miR-126-5p may serve as a prognostic factor for disease progression in sepsis-induced acute lung injury (ALI), showing its expression is linked to inflammation and immune status. This observational clinical study was conducted on a sample of 120 patients with sepsis (60 with ALI and 60 without ALI) and 120 healthy controls. The main objective of the study was to investigate the expression of miR-126-5p in the plasma of patients with sepsis-induced ALI and its correlation with inflammation and immune function indicators. The results showed that plasma miR-126-5p expression was significantly lower in patients with sepsis-induced ALI compared to patients with sepsis but no ALI (P < 0.05). In patients with sepsis-induced ALI, miR-126-5p expression was significantly and negatively correlated with CRP (P = 0.003), PCT (P = 0.003), and interleukin-6 (P < 0.001). Furthermore, the significant ability of miR-126-5p to distinguish between patients with and without ALI (AUC = 0.777, P < 0.001) supports its potential role in assessing disease severity.

In summary, recent studies confirmed the prognostic and treatment-monitoring value of miR-155[22,23], highlight the prognostic significance of miR-182[24] and miR-146b-5p[26], and miR-126-5p[27] suggest a role for miR-195 and miR-497 in guiding the timing of immunotherapy[25]. Together, these recent findings support circulating miRNAs as promising tools for prognostic stratification and treatment monitoring in sepsis and septic shock.

DISCUSSION

This review reports meaningful clinical evidence published after 2022 related to the role of circulating miRNAs in sepsis and septic shock, with emphasis on their diagnostic, prognostic, and therapeutic monitoring applications. Presented evidence confirmed the diagnostic value of previously reported biomarkers such as miR-451a and miR-9-5p, both of which demonstrated higher accuracy than conventional inflammatory markers including CRP and PCT. Additional studies identified new miRNAs with diagnostic and prognostic value, such as miR-193b-5p, miR-135a, and miR-182. Findings regarding miR-181a-5p were inconsistent, with recent case-control data showing upregulation in septic patients in contrast to earlier reports of downregulation. Beyond diagnostic applications, longitudinal assessments demonstrated that circulating miRNAs including miR-195, miR-497, and miR-182 vary dynamically with disease course and correlate with severity indices and outcomes. Translational evidence also indicated that targeting miR-93-5p may influence survival in experimental models, suggesting therapeutic potential.

The presented findings should be interpreted in the context of prior large-scale analyses.

A 2020 meta-analysis of 22 studies involving more than 3700 subjects reported that miR-223-3p provided moderate diagnostic accuracy for sepsis, with pooled sensitivity of 0.80 and specificity of 0.85[34]. This analysis established that circulating miRNAs could outperform established biomarkers such as PCT and CRP. A more recent 2023 meta-analysis including 50 studies and more than 9000 patients, confirmed the diagnostic relevance of several miRNAs and identified miR-155-5p as the marker with the highest accuracy, with pooled specificity of 0.82 and an AUC of 0.85[11]. Both of these studies positioned miR-223-3p and miR-155-5p as central diagnostic candidates. The present review extends these observations by incorporating newer studies that validate existing markers, identify additional candidates, and provide evidence for their use in prognostication and therapeutic monitoring.

Papers selected for the present review were extracted from a comprehensive literature search accomplished on PubMed directed to extract studies published between April 2022 and July 2025 using combined keywords for sepsis, septic shock, and miRNAs. Only clinical studies in adult populations and published in English were included. This strategy ensured that the review was restricted to recent and clinically relevant evidence.

A key finding of this review is that both miR-451a and miR-9-5p demonstrated higher diagnostic accuracy than conventional inflammatory markers. García-Concejo et al[14] showed that panels including miR-451a reached AUC values up to 0.96 and further improved when combined with PCT. Similarly, Ye et al[15] reported that miR-9-5p achieved AUC values above 0.82 for both sepsis and septic shock. In both studies, these miRNAs outperformed CRP and PCT, supporting the view that selected miRNAs can provide more specific and reliable diagnostic information than currently available biomarkers.

The use of miRNA in the diagnosis and therapeutic monitoring of sepsis and septic shock has significant clinical implications, primarily as a novel class of biomarkers with potential to improve early detection, risk stratification, and prognostication. Circulating miRNAs have demonstrated moderate to high diagnostic accuracy for distinguishing sepsis and septic shock from non-septic conditions, with AUC values ranging from 0.77 to 0.96 in various studies[13,35]. Panels or combinations of miRNAs (e.g., miR-100-5p, miR-148a-3p, miR-451a) further enhance diagnostic performance, especially in differentiating septic shock from other shock etiologies in postoperative patients[14]. These miRNAs often outperform or complement traditional biomarkers such as PCT and CRP, and their stability in blood samples makes them attractive for clinical use. Several miRNAs correlate with disease severity (e.g., SOFA, APACHE II scores), inflammatory markers, and short-term mortality, supporting their use in monitoring therapeutic response and predicting outcomes. For example, elevated miR-181a-5p and miR-519c-5p levels are associated with worse prognosis, while miR-193b-5p is inversely related to inflammatory burden and lymphocyte count[13,17,36]. Despite promise, clinical translation is limited by lack of standardization in sample processing, variability across patient populations, and the need for further validation in large, prospective cohorts. Current evidence supports miRNAs as adjuncts rather than replacements for established clinical and laboratory criteria[37]. The high cost of miRNA sampling limits its use in low- and middle-income countries, hindering the adoption of miRNA-based diagnostics and monitoring in sepsis. Standard quantification methods such as quantitative PCR and next-generation sequencing require specialized equipment, reagents, and expertise, resulting in substantial per-sample expenses far exceeding those of conventional biomarkers like CRP or PCT[37,38]. Reducing these costs is essential for the widespread clinical implementation of miRNA-based tools for sepsis management.

Given the rapidly expanding body of evidence on molecular biomarkers, including miRNAs, lncRNAs, and chemokines, future updates of the Surviving Sepsis Campaign guidelines could consider their integration into diagnostic and prognostic frameworks, once sufficient validation and cost standardization are achieved.

There are several possible limitations in this review: The majority of available studies were single-center and observational, often with limited sample sizes. Considerable heterogeneity exists in study populations, definitions of sepsis, and laboratory procedures for miRNA extraction and quantification. Standardized pre-analytical and analytical protocols are not yet established, and multicenter prospective validation studies are lacking. These limitations restrict direct comparability and the immediate clinical applicability of the findings. At the same time, the review also has strengths. It provides an updated synthesis restricted to recent clinical evidence, identifies new diagnostic and prognostic candidates, and highlights the role of serial monitoring. By integrating diagnostic, prognostic, and therapeutic perspectives, it illustrates the broader applicability of miRNAs beyond single-time diagnostic use.

CONCLUSION

Circulating miRNAs represent promising biomarkers for sepsis and septic shock, offering novel opportunities for early diagnosis, risk stratification, and therapeutic monitoring. Established candidates such as miR-451a and miR-9-5p have been validated in recent clinical studies, while newly identified miRNAs including miR-193b-5p, miR-135a, and miR-182 further expand diagnostic and prognostic capabilities. Conflicting evidence on miR-181a-5p underscores the need for continued validation in larger cohorts. Dynamic variations in miR-195 and miR-497 suggest that serial profiling may capture disease trajectory and support individualized treatment timing. Translation into clinical practice, however, requires multicenter validation, methodological standardization, and integration of miRNA panels into predictive algorithms. Overall, circulating miRNAs represent a significant step forward toward precision medicine in sepsis, bridging molecular diagnostics with personalized therapeutic strategies.