New Blood Test Marks Progress in Battle Against Sepsis

The immune response releases inflammatory proteins into the bloodstream, causing blood clots to form and vessels to leak. This impedes blood flow and leads to organ damage. The progress of sepsis is often unpredictable and rapid. It is a significant cause of hospital deaths and readmission.

A team of scientists led by the Cincinnati Children’s Hospital Medical Center (Cincinnati, OH, USA) developed the Pediatric Sepsis Biomarker Risk Model (PERSEVERE) to estimate mortality risk and proposed its use as a prognostic enrichment tool in sepsis clinical trials; prognostic enrichment selects patients based on mortality risk independent of treatment. It assesses five markers in the blood to predict who is at low, medium, and high risk of death. With this knowledge, doctors could start treating the serious condition much earlier and with more precision.

In a prospective cohort of 461 children with widely differing risk levels who were receiving intensive care for sepsis, the blood panel reliably predicted who would develop severe sepsis and accurately distinguished between pediatric survivors and non-survivors of sepsis at 28 days. The cohort was enrolled from a number of pediatric care centers across the country. The overall mortality rate was 12.6%. PERSEVERE includes C-C chemokine ligand 3 (CCL3), interleukin 8 (IL8), heat shock protein 70 kDa 1B (HSPA1B), granzyme B (GZMB), and matrix metallopeptidase 8 (MMP8). Biomarker concentrations were measured in a Luminex 100/200 System (Luminex Corporation, Austin, TX, USA).

The investigators also found that blood bacterial loads were higher in children who were at greater risk of dying. That finding echoes the group's previous results in mice, which showed that a higher-dose antibiotic rather than a high-dose anti-inflammatory was able to control the infections. Together, the observations indicate that a greater bacterial burden rather than excessive inflammation is the main pathologic impetus of sepsis.

Hector R. Wong, MD, a director of critical care medicine and senior investigator of the study, said, “This approach is not about diagnosis, who does or doesn't have sepsis. It's about asking among those with sepsis who's at risk for poor outcome, and we were impressed how well the model performed.” The study was published on November 13, 2019 in the journal Science Translational Medicine.

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Cincinnati Children’s Hospital Medical Center
Luminex Corporation