The accuracy of novel antigen rapid diagnostics for SARS-CoV-2: a living systematic review and meta-analysis

Abstract

Background: SARS-CoV-2 antigen rapid diagnostic tests (Ag-RDTs) are increasingly being inte-grated 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 (sensi-tivity and specificity) of commercially available Ag-RDTs. Methods: We registered the review on PROSPERO (Registration number: CRD42020225140). We systematically searched multiple databases (PubMed, Web of Science Core Collection, medRvix and bioRvix, FINDdx) for publications up until December 11th, 2020. Descriptive analyses of all studies were performed and when more than four studies were avail-able, a random-effects meta-analysis was used to estimate pooled sensitivity and specificity in comparison to reverse transcriptase polymerase chain reaction testing. We assessed heterogeneity by subgroup analyses ((1) performed conform with manufacturers instructions for use (IFU) or not, (2) symptomatic vs. asymptomatic, (3) duration of symptoms less than seven days vs. more than seven days, (4) Ct-value <25 vs. <30 vs. >30, (5) by sample type)) and with meta-regression. We assessed study quality and risk of bias using the QUADAS 2 assessment tool. Results: From a total of 11,715 articles, we extracted 98 analytical and clinical data sets. 74 clinical accuracy data sets were evaluated that included 31,202 samples. Across all meta-analyzed samples, the pooled Ag-RDT sensitivity was 73.8% (CI 68.6 to 78.5). If analysis was re-stricted to studies that followed the Ag-RDT manufacturers instructions using fresh upper res-piratory swab samples, the sensitivity increased to 79.1% (95%CI 75.0 to 82.8). The SD Biosensor Standard Q and Abbott Panbio showed the highest sensitivity with 81.7% and 72.7%, respectively. The best Ag-RDT performance was found with nasopharyngeal sampling (77.3%, CI 72.0 to 81.9) in comparison to other sample types (e.g., anterior nasal or mid turbinate 63.5%, CI 49.5 to 75.5). Testing in the first week from symptom onset resulted in higher sensitivity (87.5%, CI 86.0 to 89.1) compared to testing after one week (64.1%, CI 54.4 to 73.8). The tests performed markedly better on samples with lower Ct-values, i.e., <30 (87.9%, CI 86.7 to 88.8), in comparison to those with Ct >30 (47.8%, CI 41.1 to 54.5). Bias concerns were raised across all data sets, and financial support from the manufacturer was reported in 28.2% of data sets. Conclusion: As Ag-RDTs detect most cases within the first week of symptom onset and those with high viral load, they can have high utility for screening purposes in the early phase of disease, and thus can be a valuable tool to fight the spread of SARS-CoV-2. Standardization of con-duct and reporting of clinical accuracy studies would improve comparability and use of data.

Field evaluation of specificity and sensitivity of a standard SARS-CoV-2 antigen rapid diagnostic test: A prospective study at a teaching hospital in Northern Ghana

“…Our study demonstrates a limited sensitivity (64%) and very low specificity (81%) for a WHO approved SARS-CoV-2 Ag-RDT, which is much below the performance demonstrated in systematic reviews (sensitivity (73,8%) and specificity (99,7%) (Brümmer et al 2021).…”

“…Single use, lateral flow, antigendetection rapid diagnostic tests (Ag-RDTs) are a cheaper and easy to use alternative to RT-PCR tests. They are considered as a useful supplement to RT-PCR testing, in particular as they mainly identify cases in the early phase of disease and with high viral load and thus likely to be infective, and as they provide results within 15 minutes (Dinnes et al 2021, Brümmer et al 2021). An increasing number of Ag-RDTs have become authorized by the US Food and Drug Administration (FDA) and other health authorities, which have been shown to be highly specific, but not as sensitive as molecular tests (Peeling et al 2021).…”

Head-to-head performance comparison of self-collected nasal versus professional-collected nasopharyngeal swab for a WHO-listed SARS-CoV-2 antigen-detecting rapid diagnostic test

“…Berger et al found the Panbio to also perform similar to the Roche SARS-CoV-2 Ag-RDT (which is also distributed in parts of the world by the original equipment manufacturer SD Biosensor as STANDARD™ Q COVID-19 Ag) [10]. And the two tests were confirmed to be the best performing Ag-RDTs in two meta-analyses recently published on the topic [12,13]. Studies that show lower sensitivity on either of the two tests (e.g.…”

Interpreting a lateral flow SARS-CoV-2 antigen test

“…A large number of SARS-CoV-2 antigen LFD tests are available internationally. 9 In the UK the Innova test is approved by the Medicines and Healthcare products Regulatory Agency to identify covid-19 in people who do not have symptoms and is the only test widely used. 10 The US drug and device regulator, the Food and Drug Administration, has not approved the Innova test and in June 2021 issued a safety communication warning the public not to use the test based on concerns that its performance had not been adequately established.…”