Blood Host-Response mRNA Assays in Adult Acute Care: Diagnostic Performance, Translational Evidence, and the Clinical Implementation Gap.

Blood host-response messenger RNA (mRNA) assays provide a complementary approach to evaluating suspected acute infection by measuring the patient's transcriptional response. Fixed multigene assays can distinguish infection from noninfectious inflammation and estimate bacterial or viral likelihood, and several rapid platforms have demonstrated clinically relevant diagnostic performance in emergency and critical-care populations. This critical narrative review synthesizes representative evidence from fixed blood host-response mRNA assays in adult acute care. Structured searches of PubMed/MEDLINE, Embase, and Web of Science Core Collection were completed through August 12, 2026, and were supplemented by citation tracking and assay-specific update searches through September 2, 2026. We examine evidence by assay generation, patient-source independence, prespecified operating points, and workflow characteristics, with particular attention to the distinction between diagnostic performance and clinical utility. Current evidence is strongest for clinical validity and implementation feasibility, whereas evidence that test-guided use safely improves antimicrobial management or patient outcomes remains limited. We therefore propose a staged conceptual framework linking fixed-assay validation and prespecified operating points to representative recruitment, end-to-end workflow, clinician-visible reporting, test-guided clinical evaluation, and prospectively measured safety, patient, and resource outcomes. This framework is intended to organize translational evidence and identify the steps still required before routine clinical utility can be established.