• Roman A Lukaszewski, Helen E Jones, Vivian H Gersuk, Paul Russell, Andrew Simpson, David Brealey, Jonathan Walker, Matt Thomas, Tony Whitehouse, Marlies Ostermann, Alexander Koch, Kai Zacharowski, Mogens Kruhoffer, Damien Chaussabel, and Mervyn Singer.
• Defence Science and Technology Laboratory, Porton Down, Salisbury, Wiltshire, UK. RALUKASZEWSKI@mail.dstl.gov.uk.
• Intensive Care Med. 2022 Sep 1; 48 (9): 113311431133-1143.

PurposeEarly accurate diagnosis of infection ± organ dysfunction (sepsis) remains a major challenge in clinical practice. Utilizing effective biomarkers to identify infection and impending organ dysfunction before the onset of clinical signs and symptoms would enable earlier investigation and intervention. To our knowledge, no prior study has specifically examined the possibility of pre-symptomatic detection of sepsis.MethodsBlood samples and clinical/laboratory data were collected daily from 4385 patients undergoing elective surgery. An adjudication panel identified 154 patients with definite postoperative infection, of whom 98 developed sepsis. Transcriptomic profiling and subsequent RT-qPCR were undertaken on sequential blood samples taken postoperatively from these patients in the three days prior to the onset of symptoms. Comparison was made against postoperative day-, age-, sex- and procedure- matched patients who had an uncomplicated recovery (n =151) or postoperative inflammation without infection (n =148).ResultsSpecific gene signatures optimized to predict infection or sepsis in the three days prior to clinical presentation were identified in initial discovery cohorts. Subsequent classification using machine learning with cross-validation with separate patient cohorts and their matched controls gave high Area Under the Receiver Operator Curve (AUC) values. These allowed discrimination of infection from uncomplicated recovery (AUC 0.871), infectious from non-infectious systemic inflammation (0.897), sepsis from other postoperative presentations (0.843), and sepsis from uncomplicated infection (0.703).ConclusionHost biomarker signatures may be able to identify postoperative infection or sepsis up to three days in advance of clinical recognition. If validated in future studies, these signatures offer potential diagnostic utility for postoperative management of deteriorating or high-risk surgical patients and, potentially, other patient populations.© 2022. Springer-Verlag GmbH Germany, part of Springer Nature.

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