A Prospective Cohort Protocol for the Remnant Investigation in Sepsis Study

Abstract

BACKGROUND:. Sepsis is a common and deadly syndrome, accounting for more than 11 million deaths annually. To mature a deeper understanding of the host and pathogen mechanisms contributing to poor outcomes in sepsis, and thereby possibly inform new therapeutic targets, sophisticated, and expensive biorepositories are typically required. We propose that remnant biospecimens are an alternative for mechanistic sepsis research, although the viability and scientific value of such remnants are unknown. METHODS AND RESULTS:. The Remnant Biospecimen Investigation in Sepsis study is a prospective cohort study of 225 adults (age ≥ 18 yr) presenting to the emergency department with community sepsis, defined as sepsis-3 criteria within 6 hours of arrival. The primary objective was to determine the scientific value of a remnant biospecimen repository in sepsis linked to clinical phenotyping in the electronic health record. We will study candidate multiomic readouts of sepsis biology, governed by a conceptual model, and determine the precision, accuracy, integrity, and comparability of proteins, small molecules, lipids, and pathogen sequencing in remnant biospecimens compared with paired biospecimens obtained according to research protocols. Paired biospecimens will include plasma from sodium–heparin, EDTA, sodium fluoride, and citrate tubes. CONCLUSIONS:. The study has received approval from the University of Pittsburgh Human Research Protection Office (Study 21120013). Recruitment began on October 25, 2022, with planned release of primary results anticipated in 2024. Results will be made available to the public, the funders, critical care societies, laboratory medicine scientists, and other researchers.