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J Biotechnol. 2020 Feb 1;310:80-88. doi: 10.1016/j.jbiotec.2020.01.013. [Epub ahead of print]

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

Author information

1
Institute of Hygiene, Microbiology and Environmental Medicine, Medical University of Graz, Neue Stiftingtalstraße 6, 8010, Graz, Austria.
2
acib GmbH, Petersgasse 14, 8010, Graz, Styria, Austria.
3
CNA Diagnostics Inc., Suite 300, 4838 Richard Road SW, Calgary, Alberta, T3E 6L1, Canada.
4
Institute of Computational Biotechnology, Graz University of Technology, Petersgasse 14/V, 8010, Graz, Styria, Austria.
5
CNA Diagnostics GmbH, Parkring 18, 8074, Grambach, Styria, Austria.
6
Defence Research and Development Canada, Suffield Research Centre, Suffield, P.O. box 4000 Stn Main, T1A 8K6, Medicine Hat, Alberta, Canada.
7
Hochstraße 12, 8076, Vasoldsberg, Styria, Austria.
8
Clinical Division for Hematology, Medical University of Graz, Auenbruggerplatz 38D, 8036 Graz, Styria, Austria.
9
Department of Pediatrics and Adolescent Medicine, Medical University of Graz, Auenbruggerplatz 34/II, 8036, Graz, Styria, Austria.
10
Section of Infectious Diseases and Tropical Medicine, Department of Internal Medicine, Medical University of Graz, Auenbruggerplatz 15, 8036, Graz, Styria, Austria; BioTechMed Graz, Mozartgasse 12/II, 8010, Graz, Styria, Austria.
11
Department for Farm Animals and Veterinary Public Health, University Clinic for Ruminants, University of Veterinary Medicine, Veterinärplatz 1, 1210, Vienna, Austria.
12
Institute of Computational Biotechnology, Graz University of Technology, Petersgasse 14/V, 8010, Graz, Styria, Austria; CNA Diagnostics GmbH, Parkring 18, 8074, Grambach, Styria, Austria; BioTechMed Graz, Mozartgasse 12/II, 8010, Graz, Styria, Austria. Electronic address: csensen@tugraz.at.

Abstract

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.

KEYWORDS:

Circulating nucleic acids; Host-based markers; Human sepsis diagnostics

Conflict of interest statement

Declaration of Competing Interest None.

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