Abstract:Rapid diagnosis of COVID-19 is essential for instituting measures to prevent viral spread. SARS-CoV-2 antigen rapid diagnostic test (Ag-RDT) based on lateral flow immunochromatography assay (LFIA) principle can visually indicate the presence of SARS-CoV-2 antigens as a band. Ag-RDT is clinically promising as a point-of-care testing because it can give results in a short time without the need for special equipment. Although various antigen capture LFIAs are now available for rapid diagnosis for SARS-CoV-2 infec… Show more
“…A further 21 datasets were missing either sensitivity or specificity and were only considered for univariate analyses. Across the remaining 173 datasets, including any test and type of sample, the pooled sensitivity and specificity were 71…”
Section: Detection Of Sars-cov-2 Infectionmentioning
Background
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.
Methods and findings
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.
Conclusions
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.
“…A further 21 datasets were missing either sensitivity or specificity and were only considered for univariate analyses. Across the remaining 173 datasets, including any test and type of sample, the pooled sensitivity and specificity were 71…”
Section: Detection Of Sars-cov-2 Infectionmentioning
Background
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.
Methods and findings
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.
Conclusions
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.
“…Meanwhile, reverse transcription loop-mediated isothermal amplification (RT-LAMP) tests and rapid antigen tests for SARS-CoV-2 have been developed and recommended for repeated screenings, given that they are less expensive and with a shorter turnaround time than PCR tests (less than an hour vs. a day or two) ( Butler et al, 2021 ; Dao Thi et al, 2020 ; Larremore et al, 2021 ; Yang et al, 2021b ). Although these tests have lower sensitivity (the detection limit is about 10 5.0 copies/mL; Butler et al, 2021 ; Dao Thi et al, 2020 ; Miyakawa et al, 2021 ; Yang et al, 2021b ) than PCR tests, they can help mitigating SARS-CoV-2 transmission when used for population screenings ( Larremore et al, 2021 ) and contact tracing ( Quilty et al, 2021 ); in fact, the viral load threshold of infectiousness is considered to be higher than the detection limits of RT-LAMP tests and rapid antigen tests. Epidemiological studies are needed to assess whether isolation strategies based on RT-LAMP or rapid tests have a similar mitigation effect to those based on PCR testing.…”
Since the start of the COVID-19 pandemic, two mainstream guidelines for defining when to end the isolation of SARS-CoV-2-infected individuals have been in use: the one-size-fits-all approach (i.e. patients are isolated for a fixed number of days) and the personalized approach (i.e. based on repeated testing of isolated patients). We use a mathematical framework to model within-host viral dynamics and test different criteria for ending isolation. By considering a fixed time of 10 days since symptom onset as the criterion for ending isolation, we estimated that the risk of releasing an individual who is still infectious is low (0–6.6%). However, this policy entails lengthy unnecessary isolations (4.8–8.3 days). In contrast, by using a personalized strategy, similar low risks can be reached with shorter prolonged isolations. The obtained findings provide a scientific rationale for policies on ending the isolation of SARS-CoV-2-infected individuals.
“… Target Sample Probe Assay time (min) LOD Sensitivity Specificity Ref. N protein Nasopharyngeal swab / 10 / 75.6% 100% [ 152 ] N protein Nasal swab Red latex beads 20 0.65 ng mL −1 / / [ 150 ] N protein Nasopharyngeal swabs AgNP 15 250 pg mL −1 57.6% 99.5% [ 151 ] N protein Nasopharyngeal swab AuNP 30 56 copies μL −1 82.2% 100% [ 154 ] N protein Oropharyngeal swabs Europium (III) chelate microparticles 10 / 100% 100% [ 153 ] S protein Nasopharyngeal swab AuNP 30 5 μg mL −1 / / [ 145 ] S protein Saliva and nasal swab Co-Fe@hemin-peroxidase nanozyme 16 0.1 ng mL −1 / / [ 175 ] S protein Nasal swabs Red cellulose nanobeads 20 1.86×10 5 copies mL −1 / / [ 144 ] …”
Section: Lfa For Antigen Detectionmentioning
confidence: 99%
“…Combined with silver amplification technology, Miyakawa et al designed an enhanced SARS-CoV-2 antigen rapid diagnostic test for N antigen based on the AuNP-based LFIA. The silver-enhanced LFIA strip provides higher analytical sensitivity in testing N protein in nasopharyngeal swab samples than the unamplified AuNP-based LFIA [ 154 ]. Fig.…”
Since its first discovery in December 2019, the global coronavirus disease 2019 (COVID-19) pandemic caused by the novel coronavirus (SARS-CoV-2) has been posing a serious threat to human life and health. Diagnostic testing is critical for the control and management of the COVID-19 pandemic. In particular, diagnostic testing at the point of care (POC) has been widely accepted as part of the post restriction COVID-19 control strategy. Lateral flow assay (LFA) is a popular POC diagnostic platform that plays an important role in controlling the COVID-19 pandemic in industrialized countries and resource-limited settings. Numerous pioneering studies on the design and development of diverse LFA-based diagnostic technologies for the rapid diagnosis of COVID-19 have been done and reported by researchers. Hundreds of LFA-based diagnostic prototypes have sprung up, some of which have been developed into commercial test kits for the rapid diagnosis of COVID-19. In this review, we summarize the crucial role of rapid diagnostic tests using LFA in targeting SARS-CoV-2-specific RNA, antibodies, antigens, and whole virus. Then, we discuss the design principle and working mechanisms of these available LFA methods, emphasizing their clinical diagnostic efficiency. Ultimately, we elaborate the challenges of current LFA diagnostics for COVID-19 and highlight the need for continuous improvement in rapid diagnostic tests.
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