Accuracy of novel antigen rapid diagnostics for SARS-CoV-2: A living systematic review and meta-analysis

SARS-CoV-2 antigen rapid diagnostic tests (Ag-RDTs) are increasingly being integrated in testing strategies around the world. Studies of the Ag-RDTs have shown variable performance. In this systematic review and meta-analysis, we assessed the clinical accuracy (sensitivity and specificity) of commer...

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Vydáno v:	PLoS medicine Ročník 18; číslo 8; s. e1003735
Hlavní autoři:	Brümmer, Lukas E., Katzenschlager, Stephan, Gaeddert, Mary, Erdmann, Christian, Schmitz, Stephani, Bota, Marc, Grilli, Maurizio, Larmann, Jan, Weigand, Markus A., Pollock, Nira R., Macé, Aurélien, Carmona, Sergio, Ongarello, Stefano, Sacks, Jilian A., Denkinger, Claudia M.
Médium:	Journal Article
Jazyk:	angličtina
Vydáno:	United States Public Library of Science 12.08.2021 Public Library of Science (PLoS)
Témata:	Accuracy Age Factors Age groups Antigens Antigens, Viral - analysis Bias Biology and life sciences Carrier State - diagnosis Carrier State - virology Coronaviruses COVID-19 COVID-19 - diagnosis COVID-19 - etiology COVID-19 Serological Testing - methods COVID-19 Serological Testing - standards Disease transmission Humans Medicine and Health Sciences Meta-analysis Nasopharynx - virology Physical Sciences Polymerase chain reaction Reagent Kits, Diagnostic Reference Standards Research and Analysis Methods Reverse transcription Reviews SARS-CoV-2 - immunology Sensitivity and Specificity Severe acute respiratory syndrome coronavirus 2 Standardization Systematic review Viral Load Germany
ISSN:	1549-1676, 1549-1277, 1549-1676
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Shrnutí:	SARS-CoV-2 antigen rapid diagnostic tests (Ag-RDTs) are increasingly being integrated in testing strategies around the world. Studies of the Ag-RDTs have shown variable performance. In this systematic review and meta-analysis, we assessed the clinical accuracy (sensitivity and specificity) of commercially available Ag-RDTs. We registered the review on PROSPERO (registration number: CRD42020225140). We systematically searched multiple databases (PubMed, Web of Science Core Collection, medRvix, bioRvix, and FIND) for publications evaluating the accuracy of Ag-RDTs for SARS-CoV-2 up until 30 April 2021. Descriptive analyses of all studies were performed, and when more than 4 studies were available, a random-effects meta-analysis was used to estimate pooled sensitivity and specificity in comparison to reverse transcription polymerase chain reaction (RT-PCR) testing. We assessed heterogeneity by subgroup analyses, and rated study quality and risk of bias using the QUADAS-2 assessment tool. From a total of 14,254 articles, we included 133 analytical and clinical studies resulting in 214 clinical accuracy datasets with 112,323 samples. Across all meta-analyzed samples, the pooled Ag-RDT sensitivity and specificity were 71.2% (95% CI 68.2% to 74.0%) and 98.9% (95% CI 98.6% to 99.1%), respectively. Sensitivity increased to 76.3% (95% CI 73.1% to 79.2%) if analysis was restricted to studies that followed the Ag-RDT manufacturers' instructions. LumiraDx showed the highest sensitivity, with 88.2% (95% CI 59.0% to 97.5%). Of instrument-free Ag-RDTs, Standard Q nasal performed best, with 80.2% sensitivity (95% CI 70.3% to 87.4%). Across all Ag-RDTs, sensitivity was markedly better on samples with lower RT-PCR cycle threshold (Ct) values, i.e., <20 (96.5%, 95% CI 92.6% to 98.4%) and <25 (95.8%, 95% CI 92.3% to 97.8%), in comparison to those with Ct ≥ 25 (50.7%, 95% CI 35.6% to 65.8%) and ≥30 (20.9%, 95% CI 12.5% to 32.8%). Testing in the first week from symptom onset resulted in substantially higher sensitivity (83.8%, 95% CI 76.3% to 89.2%) compared to testing after 1 week (61.5%, 95% CI 52.2% to 70.0%). The best Ag-RDT sensitivity was found with anterior nasal sampling (75.5%, 95% CI 70.4% to 79.9%), in comparison to other sample types (e.g., nasopharyngeal, 71.6%, 95% CI 68.1% to 74.9%), although CIs were overlapping. Concerns of bias were raised across all datasets, and financial support from the manufacturer was reported in 24.1% of datasets. Our analysis was limited by the included studies' heterogeneity in design and reporting. In this study we found that Ag-RDTs detect the vast majority of SARS-CoV-2-infected persons within the first week of symptom onset and those with high viral load. Thus, they can have high utility for diagnostic purposes in the early phase of disease, making them a valuable tool to fight the spread of SARS-CoV-2. Standardization in conduct and reporting of clinical accuracy studies would improve comparability and use of data.
Bibliografie:	new_version ObjectType-Article-2 SourceType-Scholarly Journals-1 content type line 14 ObjectType-Feature-3 ObjectType-Evidence Based Healthcare-1 ObjectType-Article-1 ObjectType-Feature-2 content type line 23 ObjectType-Undefined-3 I have read the journal’s policy and the authors of this manuscript have the following competing interests: CMD is a member of the Editorial Board of PLOS Medicine.
ISSN:	1549-1676 1549-1277 1549-1676
DOI:	10.1371/journal.pmed.1003735