VIENNA – Irish researchers presented data Saturday at the European Society of Clinical Microbiology and Infectious Diseases global congress validating interleukin-6 as an early detection biomarker for sepsis in children, neonates, and pregnant women.
On the sidelines of the congress, Seán Whelan — a clinical microbiology trainee at Rotunda Hospital and Children's Health Ireland at Temple Street — described his team's efforts to implement routine IL-6 testing for the three groups and validate the biomarker when compared to other common sepsis biomarkers like procalcitonin (PCT), neutrophil-lymphocyte ratios, and C-reactive protein (CRP).
The study, which Whelan and his colleagues hope to publish, looked at the first year of routine implementation of IL-6 testing at the two hospitals and analyzed blood samples from 245 patients, including 111 pediatric patients, 72 pregnant women, and 62 neonates, and used the Roche Elecsys IL-6 electrochemiluminescence immunoassay to measure the presence of IL-6 in the blood, Whelan said. Roche's IL-6 immunoassay has received IVDR certification for use in the diagnosis of neonatal sepsis.
IL-6 has been studied as a biomarker of severity for inflammatory conditions like SARS-CoV-2 and sepsis, and other tests for its use in sepsis are in development. Bluejay Diagnostics, for example, is working on its Symphony IL-6 test for triage and monitoring of sepsis patients.
Whelan and colleagues assessed the performance of IL-6 as a biomarker at both the initial time of diagnosis to determine sensitivity and specificity in comparison to the three more common biomarkers, as well as through serial sampling on days one and two to determine how the biomarkers changed over time.
The researchers also sorted patients into multiple categories based on whether they were normal or experiencing systemic inflammatory response syndrome, sepsis, or septic shock. They also sorted patients based on whether they had no infection, a bacterial infection, or a viral infection.
The team found that IL-6 "responds far more rapidly to sepsis than the other biomarkers," rising one hour after the start of an infection and reaching its peak around six hours later, while the other biomarkers reached their peaks much later, Whelan said, making IL-6 a promising biomarker for early detection. IL-6 also outperformed all other biomarkers in pediatric and maternal populations and outperformed the other biomarkers except procalcitonin in neonates.
The team investigated IL-6 as a biomarker in the three high-risk cohorts because current biomarkers don't work well, and there are specific challenges when diagnosing sepsis in these populations at his sites, he added. For example, many children are treated in settings without critical care departments, so IL-6 may be useful in identifying which patients are at risk of deterioration early so they can be transferred to another location with critical care.
For pregnant women, meantime, the clinical signs of sepsis are similar to symptoms of other conditions, such as hemorrhage and preeclampsia, leading to a "lack of early recognition" of sepsis in these patients and a lack of early initiation of antibiotics, Whelan said. IL-6 may be able to help assess pregnant patients with signs of sepsis and determine whether they need further treatment for sepsis or if another condition should be investigated.
In neonates, "there's a very low rate of culture-confirmed sepsis, so we often don't get a pathogen or a definitive answer about whether this patient has sepsis or not," he said. As a result, clinicians must rely on biomarkers, and current biomarkers "don't work terribly well for that purpose."
Whelan said that to his knowledge there have been no studies on the use of IL-6 for sepsis prediction in pregnant women before this one, noting that the "health of the pregnant woman and her assessment has really not been studied." In children, there are very few studies that have investigated IL-6 testing for sepsis in a general pediatric population, he added.
He added that he'd like to see more prospective studies that investigate patient outcomes beyond what his team's study analyzed, such as mortality rates, time to antibiotic initiation, and time to admittance to the intensive care unit. He'd also like to see IL-6 included in national and international strategies and guidance for diagnosing and treating sepsis.
Whelan noted that testing for IL-6 should be included as part of the patient's broader clinical assessment and not used alone to determine whether a patient has sepsis. However, IL-6 could eventually replace other less effective biomarkers, such as CRP, in clinical practice.
"The question that IL-6 answers is 'does this patient have sepsis' or 'are they at risk of sepsis at this time,'" he said. It doesn't determine whether a patient's sepsis is improving or what kind of infection they have, he added.
IL-6 testing has become a "routine part of care" at Whelan's hospital as an add-on test, and he noted that it is "not extremely difficult" to introduce IL-6 testing for patients suspected of sepsis, especially because there are affordable, commercially available tests like Roche's.
After the study, Whelan's hospital has expanded availability of IL-6 testing to out-of-hours laboratory testing because it has "seen the diagnostic promise" of using it for sepsis in correctly selected patients.