Early identification and severity prediction of acute respiratory infection (ESAR): a study protocol for a randomized controlled trial

Guanmin Yuan, Hongyu Wang, Yuanhan Zhao, Enqiang Mao, Mengjiao Li, Ruilan Wang, Fangqing Zhou, Shanshan Jin, Ziqiang Zhang, Ke Xu, Jinfu Xu, Shuo Liang, Xiang Li, Lijing Jiang, Lu Zhang, Jieyu Song, Tao Yang, Jinxin Guo, Haocheng Zhang, Yang Zhou, Sen Wang, Chao Qiu, Ning Jiang, Jingwen Ai, Jing Wu, Wenhong Zhang, Guanmin Yuan, Hongyu Wang, Yuanhan Zhao, Enqiang Mao, Mengjiao Li, Ruilan Wang, Fangqing Zhou, Shanshan Jin, Ziqiang Zhang, Ke Xu, Jinfu Xu, Shuo Liang, Xiang Li, Lijing Jiang, Lu Zhang, Jieyu Song, Tao Yang, Jinxin Guo, Haocheng Zhang, Yang Zhou, Sen Wang, Chao Qiu, Ning Jiang, Jingwen Ai, Jing Wu, Wenhong Zhang

Abstract

Background: The outbreak of SARS-CoV-2 at the end of 2019 sounded the alarm for early inspection on acute respiratory infection (ARI). However, diagnosis pathway of ARI has still not reached a consensus and its impact on prognosis needs to be further explored.

Methods: ESAR is a multicenter, open-label, randomized controlled, non-inferiority clinical trial on evaluating the diagnosis performance and its impact on prognosis of ARI between mNGS and multiplex PCR. Enrolled patients will be divided into two groups with a ratio of 1:1. Group I will be directly tested by mNGS. Group II will firstly receive multiplex PCR, then mNGS in patients with severe infection if multiplex PCR is negative or inconsistent with clinical manifestations. All patients will be followed up every 7 days for 28 days. The primary endpoint is time to initiate targeted treatment. Secondary endpoints include incidence of significant events (oxygen inhalation, mechanical ventilation, etc.), clinical remission rate, and hospitalization length. A total of 440 participants will be enrolled in both groups.

Discussion: ESAR compares the efficacy of different diagnostic strategies and their impact on treatment outcomes in ARI, which is of great significance to make precise diagnosis, balance clinical resources and demands, and ultimately optimize clinical diagnosis pathways and treatment strategies. Trial registration Clinicaltrial.gov, NCT04955756, Registered on July 9th 2021.

Keywords: Acute respiratory infection; Multiplex PCR; Randomized controlled trials; mNGS.

Conflict of interest statement

The authors declare that they have no competing interests.

© 2022. The Author(s).

Figures

Fig. 1
Fig. 1
Study outline. *Group I will be detected by mNGS for pathogens. Group II will first receive respiratory multiplex PCR, then mNGS in severe pneumonia if multiplex PCR results are negative or inconsistent with the clinical conditions. CRP C-reactive protein test, PCT procalcitonin, ESR erythrocyte sedimentation rate, NPS nasopharynx swab, BALF bronchoalveolar lavage fluid, mNGS metagenomic next-generation sequencing
Fig. 2
Fig. 2
ESAR network. The map was acquired from: https://leafletjs.com/

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