AUTHOR=Qian Mengjia , Zhu Bijun , Zhan Yanxia , Wang Lingyan , Shen Qi , Zhang Miaomiao , Yue Lei , Wu Duojiao , Chen Hao , Wang Xiangdong , Cheng Yunfeng 

TITLE=Analysis of Negative Results of Metagenomics Next-Generation Sequencing in Clinical Practice

JOURNAL=Frontiers in Cellular and Infection Microbiology

VOLUME=Volume 12 - 2022

YEAR=2022

URL=https://www.frontiersin.org/journals/cellular-and-infection-microbiology/articles/10.3389/fcimb.2022.892076

DOI=10.3389/fcimb.2022.892076

ISSN=2235-2988

ABSTRACT=Background: To evaluate the negative results of metagenomics next-generation sequencing (mNGS) in clinical practice. 
Methods: One thousand and twenty-one samples from hospitalized patients who received mNGS test at Zhongshan Hospital Fudan University between 1 Jan 2019 and 31 Dec 2019 were analyzed. 
Results: There were 308 samples (30.17%) of negative results included. The most two negative sample types were blood (130/308) and tissue (63/308) which also accounted for the highest negative proportion in diseases. Sputum and bronchoalveolar lavage fluid (BALF) were more likely to have positive results. In false negative results (laboratory positive in some other sample types or some assays), 118 samples were included when compared to regular microbiological assays. The negative predictive value (NPV) of mNGS was 95.79% [95% confidence interval (95%CI), 93.8-97.8%] compared to culture and smear. Mycobacterium, Aspergillus, and Mycoplasma ranked in the top three of undetected pathogens list. 
Conclusions: The data showed that when mNGS result is negative, the negative prediction accuracy of the original specimen is high, however, other laboratory results and clinical symptom should be carefully considered prior diagnosis.