A Comparative Analysis of the Usefulness of Commonly Used Biomarkers for the Early Detection and Diagnosis of Sepsis

Introduction: A dysregulated host response to an infection can result in sepsis, a condition that can be fatal. Sepsis treatment and early diagnosis are essential for patient outcomes. In order to diagnose sepsis early, biomarkers are essential. Several biomarkers, including as C-reactive protein (CRP), procalcitonin (PCT), lactate, presepsin, and interleukin-6 (IL-6), are frequently used to diagnose sepsis. In this article, we will compare the sensitivity and specificity of various indicators for the diagnosis of sepsis.

C-reactive protein (CRP): Inflammation causes a rise in CRP, an acute-phase protein. One of the most often utilized indicators for the diagnosis of sepsis is CRP. According to a research by Viallon et al. (1999), CRP exhibited a 96% sensitivity and 71% specificity for the diagnosis of sepsis.

Procalcitonin (PCT): In reaction to bacterial infection, PCT, which is a precursor to calcitonin, is secreted. Another often utilized biomarker for the diagnosis of sepsis is PCT. PCT has a sensitivity of 86% and a specificity of 57% for the diagnosis of sepsis, according to a research by Harbarth et al. (2015).

Lactate is an anaerobic metabolic byproduct that rises in response to tissue hypoxia. Another often utilized indicator for the diagnosis of sepsis is lactate. According to Shapiro et al. (2005), lactate showed an 81% specificity and a 75% sensitivity for the diagnosis of sepsis.

Presepsin is a soluble portion of CD14, a lipopolysaccharide (LPS) receptor present on macrophages and monocytes. Presepsin is a potential biomarker for sepsis detection since it is secreted into the blood in response to an infection. According to a study by Behnes et al. (2018), presepsin exhibited an 89.5% sensitivity and an 84.2% specificity for the diagnosis of sepsis.

Interleukin-6 (IL-6): IL-6 is a cytokine that is generated in response to infection and inflammation. It is a pro-inflammatory cytokine. Another often utilized biomarker for the diagnosis of sepsis is IL-6. According to a study by Povoa et al. (2015), IL-6 exhibited a 71% sensitivity and 71% specificity for the diagnosis of sepsis.

Neutrophil CD64: In response to infection, neutrophils have an increased expression of this receptor. It could be used as a biomarker to diagnose sepsis. Neutrophil CD64 exhibited a sensitivity of 93.5% and a specificity of 87.5% for the diagnosis of sepsis, according to a study by Gros et al. (2015).

In response to infection, activated immune cells release a biomarker called soluble triggering receptor expressed on myeloid cells-1 (sTREM-1). It could be used as a biomarker to diagnose sepsis. According to Zhang et al.'s (2014) meta-analysis, sTREM-1 showed a pooled sensitivity and specificity of 77% and 76%, respectively, for the diagnosis of sepsis.

Adrenomedullin, a hormone that is secreted in reaction to stress and inflammation, is a precursor of pro-adrenomedullin (proADM). A promising biomarker for the diagnosis of sepsis is ProADM. ProADM exhibited a sensitivity of 79% and a specificity of 64% for the diagnosis of sepsis, according to a study by Schuetz et al. (2013).

Lipopolysaccharide-binding protein (LBP): LBP is a protein that interacts with LPS, a substance found in gram-negative bacteria's outer membrane. LBP may serve as a biomarker for the diagnosis of sepsis. LBP showed a sensitivity of 82% and a specificity of 93% for the diagnosis of sepsis, according to a research by Gibot et al. (2004).

Endothelial cell markers: Endothelial cell markers are biomarkers that show endothelial dysfunction, a feature of sepsis. Examples of these markers are angiopoietin-2 (Ang-2) and von Willebrand factor (vWF). According to a study by Chappell et al. (2013), Ang-2 and vWF have sensitivities and specificities for the diagnosis of sepsis of 83% and 77%, respectively.

Combination of Biomarker : Several research have looked into the value of combination of biomarkers to diagnose sepsis. PCT, CRP, and IL-6 together exhibited a sensitivity of 91.5% and a specificity of 85.3% for the diagnosis of sepsis, according to a study by Su et al. (2015). In a different study, Kofoed et al. (2007) discovered that a PCT and CRP combination had an 86% sensitivity and an 83% specificity for the diagnosis of sepsis.

Biomarker comparison: Frequently used biomarkers for sepsis diagnosis has been compared in several research. The effectiveness of CRP, PCT, lactate, and IL-6 in the diagnosis of sepsis was compared in a study by Povoa et al. (2015). In comparison to the other investigated biomarkers, PCT exhibited the best sensitivity (86%) and specificity (57%) according to the study. Lactate had a sensitivity of 60.4% and a specificity of 76%; CRP had a specificity of 60.4%; and IL-6 had a sensitivity and specificity of 71%.

In another study, presepsin was compared against CRP, PCT, and IL-6 in terms of its usefulness in the diagnosis of sepsis by Behnes et al. (2018). According to the research, among the examined biomarkers, presepsin had the highest sensitivity (89.5%) and specificity (84.2%). The sensitivity and specificity of CRP were 73.7%, 68.4%, and 89.5%, respectively, whereas those of PCT and IL-6 were 63.2% and 78.9%, respectively.

Tang et al. (2014) conducted a meta-analysis to examine the sepsis diagnosis accuracy of CRP, PCT, lactate, and IL-6. According to the study, PCT had the highest diagnostic accuracy, with a pooled sensitivity and specificity of 77% and 79%, respectively. Lactate had a pooled sensitivity of 63% and a pooled specificity of 79%, while CRP, IL-6, and lactate each had a pooled sensitivity of 64% and a pooled specificity of 69%.

Biomarkers have limitations:Biomarkers have some restrictions even though they are helpful for diagnosing sepsis. For instance, people with autoimmune disorders and cancer may have high biomarker levels, which might produce false-positive test findings. Additionally, not all episodes of sepsis—particularly those brought on by fungus or viruses—will result in an increase in biomarker levels.

Future Research: Work is being done to create novel biomarkers for the detection of sepsis. For instance, it has been demonstrated that microRNAs, which are tiny, non-coding RNA molecules that control gene expression, are altered in sepsis and may function as biomarkers for sepsis detection (Wang et al., 2019). In order to enhance sepsis diagnosis and risk stratification, machine learning algorithms are also being developed to incorporate numerous biomarkers and clinical aspects.

In general, biomarkers are essential for the early detection of sepsis. A number of biomarkers, including as CRP, PCT, lactate, presepsin, IL-6, neutrophil CD64, sTREM-1, proADM, LBP, and endothelial cell markers, are frequently employed to diagnose sepsis. The development of new biomarkers and machine learning algorithms for improved sepsis diagnosis and risk stratification are the main areas of active research. Combining biomarkers may help in sepsis diagnosis.

In conclusion: biomarkers are essential for sepsis early diagnosis. The following biomarkers are frequently used to diagnose sepsis: CRP, PCT, lactate, presepsin, and IL-6. The most sensitive and specific tests for the diagnosis of sepsis have been found to be PCT and presepsin. For the diagnosis of sepsis, biomarkers should be used in concert with other clinical and laboratory indicators because they have certain limitations as well.

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