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

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.,