Clinical evaluation of droplet digital PCR in the early identification of suspected sepsis patients in the emergency department: A prospective observational study Provisionally Accepted

Sen Jiang¹ Dongyang Zhao¹ Chunxue Wang¹ Xiandong Liu¹ Qian Yang¹ Xiaowei Bao¹ Tiancao Dong¹ Li Gen² Yi Gu¹ Yangqin Ye² Bingke Sun¹ Shumin Xu¹ Xiaohui Zhou¹ Lieying Fan^2* Lunxian Tang^1*

• ¹Shanghai East Hospital, School of Medicine, Tongji University, China
• ²School of Medicine, Tongji University, China

Background Rapid and accurate diagnosis of the causative agents is essential for clinical management of bloodstream infections (BSIs) that might induce sepsis/septic shock. A considerable number of suspected sepsis patients initially enter the health-care system through an emergency department (ED), hence it is vital to establish an early strategy to recognize sepsis and initiate prompt care in ED. This study aimed to evaluate the diagnostic performance and clinical value of droplet digital PCR (ddPCR) assay in suspected sepsis patients in the ED.Methods This was a prospective single-centered observational study including patients admitted to the ED from 25 October 2022 to 3 June 2023 with suspected BSIs screened by Modified Shapiro Score (MSS) score. The comparison between ddPCR and blood culture (BC) was performed to evaluate the diagnostic performance of ddPCR for BSIs.Meanwhile, correlative analysis between ddPCR and the inflammatory and prognosticrelated biomarkers were conducted to explore the relevance. Further, the health economic evaluation of the ddPCR was analyzed.Results 258 samples from 228 patients, with BC and ddPCR performed simultaneously, were included in this study. We found that ddPCR results were positive in 48.13% (103 of 214) of episodes, with identification of 132 pathogens. In contrast, BC only detected 18 positives, 88.89% of which were identified by ddPCR. When considering cultureproven BSIs, ddPCR shows an overall sensitivity of 88.89% and specificity of 55.61%, the optimal diagnostic power for quantifying BSI through ddPCR is achieved with a copy cutoff of 155.5. We further found that ddPCR exhibited a high accuracy especially in liver abscess patients. Among all the identified virus by ddPCR, EBV has a substantially higher positive rate with a link to immunosuppression. Moreover, the copies of pathogens in ddPCR were positively correlated with various markers of inflammation, coagulation, immunity as well as prognosis. With high sensitivity and specificity, ddPCR facilitates precision antimicrobial stewardship and reduces health care costs.The multiplexed ddPCR delivers precise and quantitative load data on the causal pathogen, offers the ability to monitor the patient's condition and may serve as early warning of sepsis in time-urgent clinical situations as ED.