Biomarkers for Sepsis: An Overview

Sepsis is a state of serious infection caused by an unusual response of the body’s immune system to an otherwise ordinary infection¹. In general, when the human body is invaded by an infectious agent, the body’s immune system has an inflammatory response. However, in patients with sepsis, the body’s immune system has a hyper-inflammatory response to an infectious agent. Following this abnormal inflammatory response, the body’s immune system goes into an immunosuppressive phase (weak immune system) where multiple organ dysfunction is present. Sepsis is a morbid state where the patient is prone to other types of infectious agents due to a weakened immune system¹.
Severe sepsis and associated septic shock are a leading cause of mortality in critically ill patients. Sepsis accounts for an estimated 30-50% of hospital-reported mortality². Despite various medical interventions, such as antibiotic therapy, extracorporeal membrane oxygenation, activated protein C therapy, human recombinant lactoferrin and TLR 4-blocker therapy, sepsis is associated with a poor prognosis and a high mortality rate².
The life-threatening nature of sepsis emphasizes the urgent need for early and accurate detection of sepsis. Standard microbial cultures used for the diagnosis of sepsis can be time-consuming and do not provide definite microbiological diagnosis in about one-third of septic patients². For this reason, reliable biomarkers can assist in the timely diagnosis of sepsis which can enable prompt treatment in patients.

suPAR as a Biomarker for Sepsis

suPAR is a biologic marker of immunologic activation. In septic patients, the biomarker suPAR can be easily measured in the blood or in other body fluids such as cerebrospinal fluid, bronchial washing fluid, saliva, and urine. Scientific research shows that suPAR levels are significantly higher in patients with sepsis than those without². Several studies have reported suPAR to be an informative biomarker for the severity of sepsis. suPAR is also believed to have a strong prognostic value in assessing the outcome of septic patients² . A summary of the most important studies supporting suPAR as a biomarker for sepsis are as follows:

• In 2012, a systematic review published in Intensive Care Medicine demonstrated that suPAR is superior to other biomarkers, including PCT, CRP, and sTREM-1, for predicting the prognosis of sepsis⁴.
• Another study published in 2012 in the BMC Medicine found that suPAR has a high predictive value and can be useful for triaging patients for Intensive Care Unit (ICU) admission. The study reported that high suPAR levels may indicate the need for more intense patient monitoring and treatment⁵.
• A systematic review and meta-analysis published in 2019 in the journal Shock reported that suPAR is a feasible biomarker for the timely diagnosis and prognosis of sepsis. The study also found that suPAR exhibits similar sensitivity and higher specificity for sepsis diagnosis that procalcitonin (PCT). As per the study, suPAR can also be used for differentiating sepsis from systemic inflammatory response syndrome (SIRS)⁶.
• In 2019, a systematic review and meta-analysis studied the effectiveness of six biomarkers in predicting mortality in adult patients with sepsis. The study, published in the Annals of Intensive Care, found that suPAR can provide beneficial prognostic information in adult patients with sepsis⁷.
• A 2016 systematic review and meta-analysis published in Nature found that serum suPAR could be a biomarker for the diagnosis and prognosis of bacterial infection. The study also reported that elevated suPAR levels are significantly associated with a high risk of death⁸.
• Another study published in 2016 in The American Journal of Emergency Medicine reported that suPAR levels are substantially increased in septic patients and the use of plasma suPAR levels can enhance the efficiency of sepsis diagnosis⁹.
• In 2019, a study published in the International Journal of Clinical and Laboratory Medicine reported that suPAR is actively involved in the pathophysiology of sepsis and can be easily and rapidly measured in an Emergency Department (ED)¹⁰.