key: cord-0744944-x3xcsmlf authors: Cao, Xun-Jie; Fang, Ke-Ying; Zhou, Jie; Li, Ya-Ping; Guo, Xu-Guang title: The Diagnostic Accuracy of Xpert Xpress to SARS-CoV-2: a systematic review date: 2022-01-12 journal: J Virol Methods DOI: 10.1016/j.jviromet.2022.114460 sha: d795c7bd798f6628d69a445a7bc3b64859ecde79 doc_id: 744944 cord_uid: x3xcsmlf The SARS-CoV-2 infection rate, as well as mortality rate, is high. There is an urgent need for a high-throughput, accurate and reliable method of diagnosing COVID-19 pneumonia. We included references from databases, such as PubMed, Cochrane Library, Web of Science, and Embase, and extracted data. Then, MetaDisc and STATA were used to establish forest plots and funnel plots for meta-analysis. We collected 14 articles and performed a systematic review. The following results were obtained: sensitivity and specificity were 0.97 (0.96 to 0.98) and 0.97 (0.96 to 0.98) respectively; PLR and NLR were 24.51 (16.63 to 36.12) and 0.03 (0.01 to 0.10) respectively, DOR was 975.15 (430.11 to 2210.88), and AUC was 0.9926. When Xpress detects SARS-CoV-2 in different samples, the heterogeneity is small and the specificity and sensitivity are extremely high. We recommend the employment of Xpert Xpress analysis in rapid screening. transmission of the coronaviruses. Later, it was reported that viral nucleotide could be isolated from feces and blood, which indicates that novel coronavirus may spread through other ways [7] . As of November 18, 2021, SARS-CoV-2 had a total of 254,847,065 confirmed cases worldwide, including 5,120,712 deaths [8] . In view of the above, a rapid, accurate and reliable method for COVID-19 pneumonia diagnosis is needed urgently. The GeneXpert® molecular diagnostic system is a fully-automated and integrated PCR-based nucleic acid detection system [9] . It can integrate sample preparations and quantitative PCR processes into a closed kit and complete sample preparation, nucleic acid purification and concentration, quantitative PCR amplification and detection, data analysis, and output the results automatically [10] . The Cepheid Xpert Xpress SARS-CoV-2 Test, for SARS-CoV-2 rapid detection，is a fully automated in vitro diagnostic assay that targets the envelope gene (E gene) and nucleocapsid gene (N2 gene) on the GeneXpert® platform [11] . With the global outbreak of SARS-CoV-2, rapid diagnosis is essential for the current pandemic. The routine use of real-time reverse transcription polymerase chain reaction (RT-qPCR) can process large quantities of samples at the same time, good sensitivity, and specificity. However, it also has shortcomings such as a long turnover time. In the case of high infection rate and high mortality rate of SARS-CoV-2, rapid access to test results can effectively control transmission and assist in isolation of patients and contacts [10] . In this larger context, molecular point-of-care test can be an option to providing diagnostic tests since this quick testing technology for SARS-CoV-2 plays a vital role in early diagnosis and timely control of infection [11] . The Cepheid Xpert Xpress SARS-CoV-2 Test, compared with the gold standard RT-qPCR, is convenient, fast and less demanding in laboratory technology [12] . We conducted a systematic review and meta-analysis on the performance of commercial Cepheid Xpert Xpress SARS-CoV-2 test for the identification of SARS-CoV-2. We applied various samples to the Xpert Xpress diagnostic technique and J o u r n a l P r e -p r o o f evaluated the detection efficacy and clinical auxiliary advantages of the Xpert Xpress in many aspects. The reviewer (Xun-Jie Cao) searched four online electronic databases until September 21, 2020. Databases that have been searched consist of Embase, PubMed, Cochrane Library and Web of Science. We included articles that met these requirements: (1) The data were provided as two-by-two tables (True positives (TP), true negatives (TN), false positives (FP) and false negatives (FN)), (2) full-text publications, and (3) The reference standard was viral culture or RT-PCR. The exclusion criteria consisted of (1) Meta-analysis, comments, letters and (2) Animal research. For each article that met the requirements, four investigators (Xun-Jie Cao, Ya-Ping Li, Jie Zhou, and Ke-Ying Fang) grouped in pairs, and then we independently extracted the following information: year of publication, the first author, country, sample type, reference standard, gender, sample size and data for two-by two tables. The results of data extraction were compared between the two groups. If the results are different, they will be solved through discussion. Because QUADAS-2 is a relatively subjective standard, and different people's evaluations may cause differences. We use QUADAS-2 as the standard to discuss and resolve differences in four researchers' understanding of the standard. Four researchers were divided into two groups to reviewed the quality of eligible articles respectively in terms of the inclusion and exclusion of cases and samples, the selection of diagnostic gold standards, and the setting of thresholds based on the quality assessment of the Diagnostic Accuracy Research Tool 2 (QUADAS-2) recommended by the Cochrane Collaborative Organization [13] . During the evaluation process, differences were resolved through negotiation. The quality assessment results are drawn using Revman (version 5.3) software. A total of 140 papers were retrieved, 47 duplicate articles were eliminated. According to the inclusion/exclusion criteria, 67 unrelated articles were excluded by screening the abstracts. After full-text reading, full-text articles excluded, with reasons J o u r n a l P r e -p r o o f including 1 meta-analysis, 1 comment, 3 letters, 2 notes and 5 reviews. A total of 11 articles were included. The exclusion reasons are shown in Figure S1 . Finally, we included 14 qualified articles which included a total of 1999 patients and performed the meta-analysis. A total of 14 studies and 1647 samples were included. The characteristics of eligible studies are presented in Table 1 . The sample types contain nasopharyngeal swabs, saliva specimens, sputum specimens, tracheal aspirate and bronchoalveolar lavage specimens, remnant stool specimens, and mixed specimens. The overall quality of the 14 included studies was excellent, and the results are shown in Figure 1 . Fig. 2e ), and the area under the SROC curve (AUC) was 0.9953 (Fig. 2f) . Deek's funnel plot, with a p value of 0.036 (Fig. 3) , showed that there was no significant publication bias in the included studies. Bivariate boxplot (Fig.4) showed that there were 3 articles out of the circles which indicated there was heterogeneity between articles we included. Fagan's Nomogram indicates that when the prediction probability of the sample is 50%, the probability of a positive result after the test was 98%, while the probability of a negative result was 1% (Fig. 5 ). The SARS-CoV-2 infection rate, as well as mortality rate, is high. There is an urgent need for a fast and convenient method of diagnosing COVID-19 pneumonia [8] . Cepheid Xpert Xpress assay has been FDA emergency authorized for detection of SARS-CoV-2. To understand the test performance of the Xpert Xpress assays, we compared the clinical efficacy of Xpert Xpress with other SARS-CoV-2 diagnostic techniques and found the high accuracy of Xpert Xpress test and its diagnostic advantages over other methods. At present, there are many studies that are compared with Xpert Xpress. For example, the study by Daniel Goldenberger et al. [14] compared a commercial SARS-CoV-2 specific nucleic acid testing, which proved that Xpert Xpress has good diagnostic performance. The research of Marie C. Smithgall et al. [15] also reached a similar conclusion. In addition to its good diagnostic accuracy, Xpert Xpress has an advantage in running time. can also be applied to small laboratories for accurate evaluation. However，there were some limitations of the review processes used. We only included the articles published in the English language, which may contribute to language bias. This review only included peer-reviewed studies with primary data. Despite the systematic search, there is still the possibility of missing literature. We didn't perform a subgroup analysis based on sample type due to the limitation of the amount of data. In this article, we concluded that the heterogeneity of the Cepheid Xpress SARS-CoV-2 assay in different samples is small and the detection in different samples does not reflect the limitations of the technology itself. Due to its extremely high specificity and sensitivity, the Cepheid Xpress SARS-CoV-2 assay can be used in rapid screening. It will become the mainstream method of SARS-CoV-2 detection and is superior to the existing mainstream methods in run time. The datasets used and/or analyzed during the current study are available from the corresponding author on reasonable request. The authors declare that there are no competing interests associated with the manuscript. 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