Diagnostic Value Of Metagenomic Next-sequencing For Central Nervous System Infection: A Meta-analysis

Objective: To evaluate the value of metagenomic next-generation sequencing(mNGS)in the diagnosis of central nervous system infection(ICNS)and to provide evidence-based medical evidence by using meta-analysis.Methods: Relevant studies on the application of mNGS in the diagnosis of ICNS were searched in Chinese and English databases such as CNKI,Wanfang Database,CBM,VIP Database,Pub Med,Embase,Web of Science,the Cochrane Library,Ovid Medline,and Scopus,from database establishment to December 31,2022.Literature screening was performed according to the inclusion and exclusion criteria,and the quality of the included studies was evaluated by the QUADAS-2 scale.The general information of literature,study design-related characteristics,study object characteristics,mNGS characteristics,and critical data such as true positive(TP),false positive(FP),false negative(FN),and true negative(TN)were extracted.When the threshold effect was excluded by Meta Disc 1.4,Stata 16 was used to statistical analysis.Calculated the pooled sensitivity(SEN),specificity(SPE),positive likelihood ratio(PLR),negative likelihood ratio(NLR),diagnostic odds ratio(DOR),and draw their respective forest plots according to different pathogen types.At the same time,a summary receiver-operating characteristic(SROC)curve was drawn,the area under the curve(AUC)was calculated as well.Heterogeneity was evaluated by subgroup analysis and meta-regression,publication bias was evaluated by Deek’s funnel plot,and clinical applicability was evaluated by Fagan plot.Results: A total of 8998 articles were obtained,and 62 sets of raw data from 54 articles were finally included after excluding duplicates and other non-confiming articles.Evaluation of the original study using the QUADAS-2 scale showed a high quality.The pooled SEN,SPE,PLR,NLR,DOR,and AUC of mNGS in all ICNS were0.75,0.92,9.0,0.27,and 0.89,respectively;the pooled SEN,SPE,PLR,NLR,DOR,and AUC of mNGS in viral infections were 0.49,0.91,5.6,0.56,10,and 0.70,respectively;the pooled SEN,SPE,PLR,NLR,DOR,and AUC of mNGS in tuberculous infections were 0.63,0.99,61.3,0.38,162,and 0.98,respectively;the pooled SEN,SPE,PLR,NLR,DOR,and AUC of mNGS in bacterial infections were0.69,0.83,4.1,0.37,11,and 0.83,respectively;and the pooled SEN,SPE,PLR,NLR,DOR,and AUC of mNGS in fungal infections were 0.76,0.98,0.98,0.98,respectively.Subgroup analysis and meta-regression analysis suggested that sample size,whether empirical medication was used before testing,whether the study population was adults or children,sequencing platform and sequencing range were possible sources of heterogeneity in this meta-analysis.Conclusion: mNGS has a high overall diagnostic value in ICNS;it has the very high diagnostic value in tuberculosis and fungi infections,moderate diagnostic value in bacteria infections,and fair diagnostic value in virus infections.