ArticlePloS one2025
Blood RNA biomarkers and a point-of-care elastase assay for detecting host immune activation in suspected sepsis: Trajectory matters.
Article in PloS one, 2025. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 2 papers.
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Who cites it
2 citing papers in PubMed.
- Acculturation, Social Support, and Healthcare Utilisation Among Indonesian Migrant Workers in Malaysia: A Cross-Sectional Study.Journal of racial and ethnic health disparities · 2026Article
- Genetic basis of natural variation for photosynthetic pigments in Brassica juncea leaves and silique walls under differing photoperiod conditions.TAG. Theoretical and applied genetics. Theoretische und angewandte Genetik · 2026Article
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Authors and funding
23 authors.
Funding
No grant is acknowledged in the PubMed record.
Abstract
introduction/hypothesisThe chances of survival from sepsis are improved by early diagnosis and treatment. In the prospective SENSOR study, RNA biomarkers of innate immune neutrophil activation were examined in emergency department (ED) patients triggering an automated sepsis alert. We hypothesized that higher levels of blood RNA biomarkers related to neutrophil activation would be associated with progression to more severe forms of sepsis.
methodsAdult patients in the ED triggering a sepsis alert were consented, enrolled, and study samples were obtained during the ED visit. Additionally, study samples were collected from a convenience sample of 16 adult non-ED controls and 8 other adults with self-described infectious illnesses. Blood samples were drawn in RNA preservative (Tempus) and whole blood RNA was analyzed by droplet digital PCR (ddPCR) for RNA transcripts related to neutrophil response to infection by bacterial (DEFA1; ALPL, IL8RB/CXCR2), and viral (IFI27, RSAD2) pathogens. Bacterial burden in blood was quantitated by ddPCR of 16S ribosomal DNA. Separately, neutrophil elastase was measured in immunomagnetically captured CD66b+ neutrophils by a novel point-of-care device.
resultsPatients were grouped using both 'Sepsis-2' SIRS criteria, adjudicated by independent physicians, and 'Sepsis-3' criteria which uses a qSOFA score for categorizing the severity of illness. Across 72 enrolled sepsis alert patients, 62.5% showed positive RNA biomarkers for bacterial infection, and 8.3% were positive for viral markers, with only 2 cases that showed only a viral signal. Septic patients showed a 4-fold increase in RNA markers vs. those without infection (p < 0.05). However, no significant differences were observed in RNA levels between those with sepsis vs those with more severe forms of sepsis. Likewise, RNA biomarker levels did not discriminate patients with qSOFA≥2 from qSOFA = 1. In a subset of patients with zero and three hour blood samples (n = 27) it was found that changes in RNA levels (up or down), or neutrophil elastase activity, was strongly associated with progression to more severe forms of sepsis or a qSOFA score of ≥2.
conclusionsPatients progressing to more severe forms of sepsis did not have higher absolute levels of neutrophil activation RNA biomarkers (or higher bacterial burden in blood) compared to patients with sepsis. However, a change in RNA biomarkers or elastase between zero and three hours was strongly indicative of progression to more severe forms of sepsis.
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