AUTHOR=Zhu Yunqi , Xu Miaomiao , Ding Chengyuan , Peng Zhihang , Wang Weixiao , Sun Binghu , Cheng Jian , Chen Chen , Chen Wei , Wei Hongxia , Hu Zhiliang 

TITLE=Metagenomic Next-Generation Sequencing vs. Traditional Microbiological Tests for Diagnosing Varicella-Zoster Virus Central Nervous System Infection

JOURNAL=Frontiers in Public Health

VOLUME=Volume 9 - 2021

YEAR=2022

URL=https://www.frontiersin.org/journals/public-health/articles/10.3389/fpubh.2021.738412

DOI=10.3389/fpubh.2021.738412

ISSN=2296-2565

ABSTRACT=Background: Unbiased metagenomic next-generation sequencing (mNGS) detects pathogens in a target-independent manner. It's not well understood whether mNGS has comparable sensitivity to target-dependent nucleic acid test for pathogen identification. 
Methods: This study included 31 patients with chickenpox and neurological symptoms for screening of possible varicella-zoster virus (VZV) central nervous system (CNS) infection. Microbiological diagnosing of VZV CSF infection was performed on stored cerebrospinal fluid (CSF) samples using mNGS, quantitative and qualitative VZV-specific polymerase chain reaction (PCR) assays, and VZV IgM antibodies test.
Results: The median age was 30.0 (interquartile range, 24.3-33.3) years. 51.6% of the patients were male. 80.6% of the patients had normal CSF white blood cell counts (≤ 5×106/L). VZV IgM antibodies presented in 16.1% of the CSF samples, and nucleic acids were detectable in 16.1% and 9.7% using two different VZV-specific real-time PCR protocols. Intriguingly, maximal identification of VZV elements was achieved by CSF mNGS (p=0.001 and p=007; compared with qualitative PCR and VZV IgM antibody test, respectively), with sequence reads of VZV being reported in 51.6% (16/31) of the CSF samples. All VZV PCR positive samples were positive when analyzed by mNGS. Of note, human betaherpesvirus 6A with clinical significance was unexpectedly detected in one CSF sample. 
Conclusions: Our study suggests that CSF mNGS may have higher sensitivity for VZV detection than CSF VZV PCR, and has the advantage of identifying unexpected pathogens.