Dinnes Jacqueline, Berhane Sarah, Walsh Jennifer, Reidy Paul, Doherty Aaron, Hillier Bethany, Scandrett Katie, Hettiarachchi Dineshani, Islam Fahmida, Mathangasinghe Yasith, Nyaaba Nicholas, Taylor Melissa, Weeratunga Praveen, Wickramasinghe Dakshitha, van Wyk Susanna S, Cunningham Jane, Davenport Clare, Dittrich Sabine, Emperador Devy, Hooft Lotty, Leeflang Mariska Mg, McInnes Matthew Df, Spijker René, Verbakel Jan Y, Takwoingi Yemisi, Taylor-Phillips Sian, Van den Bruel Ann, Deeks Jonathan J
Biostatistics, Evidence Synthesis, Test Evaluation and prediction Models (BESTEAM), Department of Applied Health Sciences, University of Birmingham, Birmingham, UK.
NIHR Birmingham Biomedical Research Centre, University Hospitals Birmingham NHS Foundation Trust and University of Birmingham, Birmingham, UK.
Cochrane Database Syst Rev. 2025 Nov 28;11(11):CD013705. doi: 10.1002/14651858.CD013705.pub4.
Accurate rapid diagnostic tests for SARS-CoV-2 infection could help manage the COVID-19 pandemic by potentially increasing access to testing and speed detection of infection, as well as informing clinical and public health management decisions to reduce transmission. Previous iterations of this review provided clear and conclusive evidence of superior test performance in those experiencing possible signs and symptoms of Covid-19. However, test performance in asymptomatic individuals and sensitivity by setting and indication for testing remains unclear. This is the fourth iteration of this review, first published in 2020.
To assess the diagnostic accuracy of rapid, point-of-care antigen tests (Ag-RDTs) for diagnosis of SARS-CoV-2 infection in asymptomatic population groups.
We searched the COVID-19 Open Access Project living evidence database from the University of Bern (which includes daily updates from MEDLINE and Embase and preprints from medRxiv and bioRxiv) on 17 February 2022. We included independent evaluations from national reference laboratories, FIND and the Diagnostics Global Health website. We did not apply language restrictions.
We included test accuracy studies of any design that evaluated commercially produced, rapid antigen tests in asymptomatic people tested because of known or suspected contact with SARS-CoV-2 infection, known SARS-CoV-2 infection or known absence of infection, or those who were being screened for infection. We included evaluations of single applications of a test (one test result reported per person). Reference standards for presence or absence of infection were any laboratory-based molecular test (primarily reverse transcription polymerase chain reaction (RT-PCR)).
We used standard screening procedures with three reviewers. Two reviewers independently carried out quality assessment (using the QUADAS-2 tool) and extracted study results. Other study characteristics were extracted by one review author and checked by a second. We present sensitivity and specificity with 95% confidence intervals (CIs) for each test, and pooled data using the bivariate model. We investigated heterogeneity by including indicator variables in the random-effects logistic regression models. We tabulated results by test manufacturer and compliance with manufacturer instructions for use and according to symptom status.
We included 146 study cohorts (described in 130 study reports). The main results relate to 164 evaluations of single test applications including 144,250 unique samples (7104 with confirmed SARS-CoV-2) obtained from asymptomatic or mainly asymptomatic populations. Studies were mainly conducted in Europe (85/146, 58%), and evaluated 41 different commercial antigen assays (test kit). Only six studies compared two or more brands of test. Nearly all studies (96%) used RT-PCR alone to define presence or absence of infection. Risk of bias was high because of participant selection (13, 9%); interpretation of the index test (3, 2%); weaknesses in the reference standard for absence of infection (3, 2%); and participant flow and timing (46, 32%). Characteristics of participants (11, 8%) and index test delivery (117, 80%) differed from the way in which and in whom the test was intended to be used. Estimates of sensitivity varied considerably between studies, with consistently high specificities. Average sensitivity was 55.0% (95% CI 50.9%, 59.0%) and average specificity was 99.5% (95% CI 99.5%, 99.6%) across the 147 evaluations of Ag-RDTs reporting both sensitivity and specificity (149,251 samples, 7636 cases). Average sensitivity was higher when epidemiological exposure to SARS-CoV-2 was suspected (58.6%, 95% CI 51.4% to 65.5%; 43 evaluations; 15,516 samples, 1483 cases) compared to where COVID-19 testing was reported to be widely available to anyone on presentation for testing (53.0%, 95% CI 48.4% to 57.5%; 103 evaluations; 129,032 samples, 5660 cases); however CIs overlapped, limiting the inference that can be drawn from these data. Average specificity was similarly high for both groups (99.4% and 99.6%). Sensitivity was generally lower when used in a screening context (summary values from 40.6% to 42.1% for three of four screening settings) compared to testing asymptomatic individuals at Covid-19 test centres (56.7%) or emergency departments (54.7%). We observed a decline in summary sensitivities as measures of sample viral load decreased. Sensitivity varied between brands. When tests were used according to manufacturer instructions, average sensitivities by brand ranged from 36.3% to 78.8% in asymptomatic participants (14 assays with sufficient data for pooling). None of the assays met the WHO acceptable performance standard for sensitivity (of 80%) based on meta-analysis; however, sensitivities from individual studies (where meta-analysis was not possible) exceeded 80% for three assays. The WHO acceptable performance criterion of 97% specificity was met by all but four assays (based on individual studies or meta-analysis) when tests were used according to manufacturer instructions. At 0.5% prevalence using summary data for asymptomatic people, where testing was widely available and where epidemiological exposure to COVID-19 was suspected, resulting PPVs would be 40% and 33%, meaning that 3 in 5 or 2 in 3 positive results will be false positives, and between 1 in 2 and 2 in 5 cases will be missed.
AUTHORS' CONCLUSIONS: Evidence for antigen testing in asymptomatic cohorts has increased considerably since the publication of the previous update of this review. Average sensitivities remain lower for testing of asymptomatic when compared to symptomatic individuals; however, there is an indication that sensitivities may be higher where epidemiological exposure to SARS-CoV-2 is suspected compared to testing any asymptomatic individual regardless of indication. Sensitivities were particularly low when antigen tests were used in screening settings. Assays from different manufacturers also vary in sensitivity, indicating the need for appropriate clinical validation of a particular antigen test in a given intended use setting prior to more widespread deployment. Further research is needed to evaluate the effectiveness of screening programmes at reducing transmission of infection, whether mass screening or targeted approaches, including schools, healthcare setting and traveller screening.
This paper presents independent research supported by the NIHR Birmingham Biomedical Research Centre, University Hospitals Birmingham NHS Foundation Trust, and the University of Birmingham. The views expressed are those of the author(s) and not necessarily those of the NHS, the NIHR or the Department of Health and Social Care.
Protocol (2020) doi: 10.1002/14651858.CD013596.
针对严重急性呼吸综合征冠状病毒2（SARS-CoV-2）感染的准确快速诊断测试，可能通过增加检测机会、加快感染检测速度，以及为临床和公共卫生管理决策提供信息以减少传播，从而有助于应对2019冠状病毒病（COVID-19）大流行。本综述的前几版提供了明确且确凿的证据，证明在出现COVID-19可能体征和症状的人群中，测试性能更优。然而，无症状个体的测试性能以及不同检测场景和检测指征下的敏感性仍不明确。这是本综述的第四次更新版本，首次发表于2020年。
评估即时快速抗原检测（Ag-RDT）在无症状人群中诊断SARS-CoV-2感染的诊断准确性。
我们于2022年2月17日检索了伯尔尼大学的COVID-19开放获取项目实时证据数据库（其中包括来自MEDLINE和Embase的每日更新内容以及来自medRxiv和bioRxiv的预印本）。我们纳入了来自国家参考实验室、FIND以及诊断全球健康网站的独立评估。我们未设语言限制。
我们纳入了任何设计的测试准确性研究，这些研究评估了因已知或疑似接触SARS-CoV-2感染、已知SARS-CoV-2感染或已知未感染而接受检测的无症状人群，或正在接受感染筛查的人群中商业生产的快速抗原检测。我们纳入了对单次测试应用的评估（每人报告一个测试结果）。感染存在与否的参考标准为任何基于实验室的分子检测（主要是逆转录聚合酶链反应（RT-PCR））。
我们采用标准筛选程序，由三位审阅者进行。两位审阅者独立进行质量评估（使用QUADAS-2工具）并提取研究结果。其他研究特征由一位综述作者提取，并由另一位作者进行核对。我们给出了每项测试的敏感性和特异性及其95%置信区间（CI），并使用双变量模型汇总数据。我们通过在随机效应逻辑回归模型中纳入指示变量来研究异质性。我们按测试制造商、是否符合制造商使用说明以及症状状态列出结果。
我们纳入了146个研究队列（在130篇研究报告中描述）。主要结果涉及对164次单次测试应用的评估，包括从无症状或主要无症状人群中获取的144,250个独特样本（7104个确诊为SARS-CoV-2感染）。研究主要在欧洲进行（85/146，58%），并评估了41种不同的商业抗原检测方法（试剂盒）。只有六项研究比较了两种或更多品牌的检测。几乎所有研究（96%）仅使用RT-PCR来定义感染的存在与否。由于参与者选择（13项，9%）、指标测试的解释（3项，2%）、未感染的参考标准存在缺陷（3项，2%）以及参与者流程和时间安排（46项，32%），偏倚风险较高。参与者特征（11项，8%）和指标测试实施方式（117项，80%）与测试的预期使用方式和对象不同。各研究间敏感性估计差异很大，特异性始终较高。在报告了敏感性和特异性的147次Ag-RDT评估（149,251个样本，7636例病例）中，平均敏感性为55.0%（95%CI 50.9%，59.0%），平均特异性为99.5%（95%CI 99.5%，99.6%）。与报告COVID-19检测对任何前来检测者广泛可用的情况相比，当怀疑有SARS-CoV-2的流行病学暴露时，平均敏感性更高（58.6%，95%CI 51.4%至；43次评估；15,516个样本，1483例病例）（53.0%，95%CI 48.4%至57.5%；103次评估；129,032个样本，5660例病例）；然而，置信区间有重叠，限制了从这些数据中得出的推断。两组的平均特异性同样较高（分别为99.4%和99.6%）。与在COVID-19检测中心（56.7%）或急诊科（54.7%）对无症状个体进行检测相比，在筛查背景下使用时，敏感性通常较低（四个筛查场景中的三个场景的汇总值为40.6%至42.1%）。我们观察到随着样本病毒载量测量值的降低，汇总敏感性下降。不同品牌的敏感性有所不同。当按照制造商说明使用检测时，无症状参与者中各品牌的平均敏感性范围为36.3%至78.8%（14种检测方法有足够数据进行汇总）。基于荟萃分析，没有一种检测方法达到世界卫生组织（WHO）可接受的80%敏感性性能标准；然而，对于三种检测方法，个别研究（无法进行荟萃分析）的敏感性超过了80%。当按照制造商说明使用检测时，除四项检测方法外（基于个别研究或荟萃分析），所有检测方法均符合WHO 97%特异性的可接受性能标准。在无症状人群中，当患病率为0.5%时，在检测广泛可用且怀疑有COVID-19流行病学暴露的情况下，阳性预测值（PPV）将分别为40%和33%，这意味着五分之三或三分之二的阳性结果将为假阳性，并且将漏诊二分之一至五分之二的病例。
自本综述上次更新发表以来无症状队列中抗原检测的证据大幅增加。与有症状个体相比，无症状检测的平均敏感性仍然较低；然而，有迹象表明，与对任何无症状个体进行检测（无论检测指征如何）相比，在怀疑有SARS-CoV-2流行病学暴露的情况下，敏感性可能更高。当抗原检测用于筛查背景时，敏感性特别低。不同制造商的检测方法在敏感性方面也存在差异，这表明在更广泛应用之前，需要在给定的预期使用场景中对特定抗原检测进行适当的临床验证。需要进一步研究来评估筛查计划在减少感染传播方面的有效性，无论是大规模筛查还是针对性方法，包括学校、医疗机构和旅行者筛查。
本文呈现了由英国国家卫生研究院（NIHR）伯明翰生物医学研究中心、伯明翰大学医院国民保健服务信托基金和伯明翰大学支持的独立研究。所表达的观点是作者的观点，不一定代表国民保健服务体系、NIHR或卫生与社会保健部的观点。
方案（2020）doi: 10.1002/14651858.CD013596
