Antigen rapid diagnostic tests (Ag-RDT) for detecting SARS-CoV-2 infection perform better in patients with increased viral loads, when used within the first week after symptom onset, and when used as directed by manufacturers’ recommendations, according to results of a meta-analysis published in PLoS Medicine.
In this systematic review and meta-analysis, researchers reviewed 133 analytical and clinical studies to assess the clinical accuracy of 61 different Ag-RDTs. The included studies comprised214 clinical datasets with a total of 112,323 samples. The sensitivity and specificity of Ag-RDTs were compared with standard reverse transcription polymerase chain reaction (RT-PCR) testing in all studies, with the exception of 1 which used viral culture testing.
Of 214 clinical datasets, 41 were excluded due to either having fewer than 20 positive RT-PCR samples or a lack of sensitivity and specificity information. In the remaining 173 datasets, the pooled sensitivity and specificity were 71.2% (95% CI, 68.2-74.0) and 98.9% (95% CI, 98.6-99.1), respectively. When analysis was restricted to 81 datasets with 49,643 samples that were tested via manufacturers’ recommendations, sensitivity and specificity increased to 76.3% (95% CI, 73.1-79.2) and99.1% (95% CI, 98.8–99.4), respectively.
Using information obtained from 119 datasets with 71,424 samples, the researchers performed a bivariate meta-analysis of 12 different Ag-RDTs. Analysis showed that the LumiraDx and Lumipulse G SARS-CoV-2 infection tests were associated with an 88.2% (95% CI, 59.0-97.5) and 87.2% (95% CI, 78.0-92.9) increase in pooled sensitivity, respectively. The Panbio test, which has been approved for emergency use by the World Health Organization (WHO), had a pooled sensitivity of 71.8% (95% CI, 65.4-77.5). Of the non-instrument tests, the Standard F and Standard Q tests by SD Biosensor were found to perform best, with pooled sensitivities of 80.2% (95% CI, 70.3-87.4) and 74.9% (95% CI, 69.3-79.7), respectively. The pooled specificity for all test types was greater than 98%.
Subgroup analysis showed that pooled sensitivity was increased among test samples with a cycle threshold (Ct) value of less than 25 (95.8%; 95% CI, 92.3-97.8) compared with those with a Ct value greater than or equal to 25 (50.7%; 95% CI, 35.6-65.8). In addition, symptomatic patients had a markedly increased pooled sensitivity compared with those who were asymptomatic: 76.7% (95% CI, 70.6-81.9) vs 52.5% (95% CI, 43.7-61.1). Similar results were observed among patients whose onset of symptoms began in less than 7 days vs those with symptom onset after 7 or more days: 83.8% (95% CI, 76.3-89.2) vs 61.5% (95% CI, 52.2-70.0).
On analysis of sample collection method, anterior and mid-turbinate nasopharyngeal swab testing (32 datasets and 25,814 samples) had mildly increased sensitivity when compared with nasopharyngeal/oropharyngeal swab testing (122 datasets and 59,810 samples): 75.5% (95% CI, 70.4-79.9) vs 71.6% (95% CI, 68.1-74.9).
Limitations of this study included its heterogeneity among the studies included in the analysis, concerns of bias across all datasets, and the inclusion of studies which received financial support from the manufacturer and/or employment of study authors by the manufacturer.
“The accuracy achievable by the best-performing Ag-RDTs, combined with the rapid turnaround time compared [with] RT-PCR [testing], suggests that these tests could have a significant impact on the [COVID-19] pandemic if applied in thoughtful testing and screening strategies,” the researchers concluded.
Disclosure: One author declared an affiliation with the Editorial Board of PLoS Medicine. Please see the original reference for a full list of disclosures.
Brummer LE, Katzenschlager S, Gaeddert M, et al. Accuracy of novel antigen rapid diagnostics for SARS-CoV-2: A living systematic review and meta-analysis. PLoS Med. 2021;18(8):e1003735. doi:10.1371/journal.pmed.1003735