Clinical Application of High-throughput Sequencing Technology for the Diagnosis of Patients With Severe Infection

The purpose of this study is to evaluate the clinical value of high throughput sequencing of infectious pathogens for patients with severe infection, and to establish foundation for high throughput sequencing to be the clinical routine infection pathogen examination.

This study is a diagnostic study, and the sample size is 320 cases. 320 participants from the department of hematology and intensive care unit who meet the inclusion criteria are randomly divided into the control group and the experimental group with 160 cases in each group. Both the participants of the control group and the experimental group undergo routine clinical diagnosis methods and treatment. In addition, the participants of the experimental group are collected the samples including whole blood, cerebrospinal fluid or alveolar lavage fluid required for high throughput sequencing of infectious pathogens during sample collection for routine pathogenic examination of infection. For the experimental group participants, the clinicians will comprehensively determine the follow-up diagnosis methods and treatment according to the clinical routine infection pathogen tests results combining with the results of high throughput sequencing of infectious pathogen, while the control group participants proceed to undergo follow-up diagnosis methods and treatment according to the results of the clinical routine infection pathogen examination. If the results of high throughput sequencing of infectious pathogens of the test group are inconsistent with the results of clinical routine infection pathogen examination, the follow-up diagnosis and treatment of the participants will be based on the results of clinical routine infection pathogen examination with priority.

For sample size assessment, we have predicted the pathogen diagnosis rate of routine clinical pathogen detection methods and high-throughput sequencing of infectious pathogens (α=0.05, β=0.10 (power=0.9)), considering that the maximum rate of missing cases was 20%, and finally got the sample content. And this study will include all subjects selected and randomized into a full analysis set under the intent-to-treat principle. After excluding participants with insufficient sample, withdrawing from the trial midway, giving up treatment and leaving the hospital, or lost to follow-up, the remaining participants will be included in the protocol set under the per-protocol principle.

As for statistical analysis, the pathogen diagnosis rate and the diagnostic accuracy rate between the conventional infectious pathogen tests and the high throughput sequencing of infectious pathogens will be compared in the experimental group. By gathering statistics of consultation hours and cost efficiency, the effect of high throughput sequencing of infectious pathogens on the diagnosis and treatment efficiency of the experimental group and the control group will be compared, and through these indicators, clinical application value for the diagnosis of severe infection patients by high throughput sequencing of infectious pathogens can be evaluated.