Accuracy and ease-of-use of seven point-of-care SARS-CoV-2 antigen-detecting tests: A multi-centre clinical evaluation

Abstract

Background: Antigen-detecting rapid diagnostic tests (Ag-RDTs) for SARS-CoV-2 are important diagnostic tools. We assessed clinical performance and ease-of-use of seven Ag-RDTs in a prospective, manufacturer-independent, multi-centre cross-sectional diagnostic accuracy study to inform global decision makers.

Methods: Unvaccinated participants suspected of a first SARS-CoV-2 infection were recruited at six sites (Germany, Brazil). Ag-RDTs were evaluated sequentially, with collection of paired swabs for routine reverse transcription polymerase chain reaction (RT-PCR) testing and Ag-RDT testing. Performance was compared to RT-PCR overall and in sub-group analyses (viral load, symptoms, symptoms duration). To understandusability a System Usability Scale (SUS) questionnaire and ease-of-use (EoU) assessment were performed.

Findings: 7471 participants were included in the analysis. Sensitivities across Ag-RDTs ranged from 70·4%-90·1%, specificities were above 97·2% for all Ag-RDTs but one (93·1%).Ag-RDTs, Mologic, Bionote, Standard Q, showed diagnostic accuracy in line with WHO targets (> 80% sensitivity, > 97% specificity). All tests showed high sensitivity in the first three days after symptom onset (≥87·1%) and in individuals with viral loads≥ 6 log₁₀SARS-CoV2 RNA copies/mL (≥ 88·7%). Usability varied, with Rapigen, Bionote and Standard Q reaching very good scores; 90, 88 and 84/100, respectively.

Interpretation: Variability in test performance is partially explained by variable viral loads in population evaluated over the course of the pandemic. All Ag-RDTs reach high sensitivity early in the disease and in individuals with high viral loads, supporting their role in identifying transmission relevant infections. For easy-to-use tests, performance shown will likely be maintained in routine implementation.

Funding: Ministry of Science, Research and Arts, State of Baden-Wuerttemberg, Germany, internal funds from Heidelberg University Hospital, University Hospital Charité - Universitätsmedizin Berlin, UK Department of International Development, WHO, Unitaid.

Keywords: Antigen-detecting rapid diagnostic tests; COVID-19; SARS-CoV-2; Sensitivity; Specificity.

Figure 1

Overall Performance for Ag-RDTs. N = Total number of cases included in analysis, TP = True Positives, FN = False Negatives, TN = True Negatives, FP = Faklse Positives, dashed red lines = WHO TPP cut-offs.

Figure 2

Performance of Ag-RDTs based on subgroup analysis. D+ = Number of PCR positive cases inlcuded in analysis, TP = True Positives, FN = False Negatives.

Figure 3

Viral load for each test compared to Ag-RDT results. FN = False Negatives, TP = True Positives.

Figure 4

System Usability Score and Ease-of-Use assessment results. The SUS score for each test is the mean score of all respondents who filled in the SUS (supplement material). The heat map includes the different aspects of the tests which were assessed by at least 3 respondents in the EoU survey (supplement material). The heat map was generated using a pre-defined matrix (Fig. S2). Number of participants: GE – Germany and BRA – Brazil Rapigen: 8 (6 GE, 2 BRA), SDF: 13 (7 GE, 6 BRA), SDQ: 13 (6 GE, 7 BRA), Bioeasy: 8 (8 GE, 0 BRA), Fujirebio: 6 (6 GE, 0 BRA), Bionote: 3 (0 GE, 3 BRA), Mologic: 6 (6 GE, 0 BRA).