Evaluation of host-based molecular markers for the early detection of human sepsis

• Published in: Journal of biotechnology Vol. 310; pp. 80 - 88
• Main Authors: Ullrich, Elisabeth, Heidinger, Petra, Soh, Jung, Villanova, Laura, Grabuschnig, Stefan, Bachler, Thorsten, Hirschböck, Elisabeth, Sánchez-Heredero, Sara, Ford, Barry, Sensen, Maria, Rosales Rodriguez, Ingund, Schwendenwein, Daniel, Neumeister, Peter, Zurl, Christoph J., Krause, Robert, Lorenz Khol, Johannes, Sensen, Christoph W.
• Format: Journal Article
• Language: English
• Published: Netherlands Elsevier B.V 20.02.2020
• Subjects: Adolescent; Adult; Aged; Aged, 80 and over; Biomarkers - blood; Circulating nucleic acids; Cohort Studies; DNA, Bacterial - blood; DNA, Bacterial - genetics; DNA, Fungal - blood; DNA, Fungal - genetics; Female; Host-based markers; Human sepsis diagnostics; Humans; Male; Middle Aged; Real-Time Polymerase Chain Reaction; Sepsis - blood; Sepsis - genetics; Sepsis - microbiology; Circulating nucleic acids; Host-based markers; Human sepsis diagnostics
• ISSN: 0168-1656; 1873-4863
• DOI: 10.1016/j.jbiotec.2020.01.013

•Assay is based on host-response, NOT on pathogen detection•Assay detects sepsis 2–3 days before the first clinical signs•Assay is robust (DNA-based)•Assay uses serum or plasma without further isolation/purification steps We have identified 24 molecular markers, based on circulating nucleic acids (CNA) originating from the human genome, which in combination can be used in a quantitative real-time PCR (qPCR) assay to identify the presence of human sepsis, starting two to three days before the first clinical signs develop and including patients who meet the SEPSIS-3 criteria. The accuracy was more than 87 % inside of the same patient cohort for which the markers were developed and up to 81 % in blind studies of patient cohorts which were not included in the marker development. As our markers are host-based, they can be used to capture bacterial as well as fungal sepsis, unlike the current PCR-based tests, which require species-specific primer sets for each organism causing human sepsis. Our assay directly uses an aliquot of cell-free blood as the substrate for the PCR reaction, thus allowing to obtain the diagnostic results in three to four hours after the collection of the blood samples.