The Comparative Clinical Performance of Four SARS-CoV-2 Rapid Antigen Tests and Their Correlation to Infectivity In Vitro

Abstract

Due to globally rising numbers of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infections, resources for real-time reverse-transcription polymerase chain reaction (rRT-PCR)-based testing have been exhausted. In order to meet the demands of testing and reduce transmission, SARS-CoV-2 antigen-detecting rapid diagnostic tests (Ag-RDTs) are being considered. These tests are fast, inexpensive, and simple to use, but whether they detect potentially infectious cases has not been well studied. We evaluated three lateral flow assays (RIDA®QUICK SARS-CoV-2 Antigen (R-Biopharm), SARS-CoV-2 Rapid Antigen Test (Roche)), and NADAL® COVID-19 Ag Test (Nal von Minden GmbH, Regensburg, Germany) and one microfluidic immunofluorescence assay (SARS-CoV-2 Ag Test (LumiraDx GmbH, Cologne, Germany)) using 100 clinical samples. Diagnostic rRT-PCR and cell culture testing as a marker for infectivity were performed in parallel. The overall Ag-RDT sensitivity for rRT-PCR-positive samples ranged from 24.3% to 50%. However, for samples with a viral load of more than 6 log10 RNA copies/mL (22/100), typically seen in infectious individuals, Ag-RDT positivity was between 81.8% and 100%. Only 51.6% (33/64) of the rRT-PCR-positive samples were infectious in cell culture. In contrast, three Ag-RDTs demonstrated a more significant correlation with cell culture infectivity (61.8–82.4%). Our findings suggest that large-scale SARS-CoV-2 Ag-RDT-based testing can be considered for detecting potentially infective individuals and reducing the virus spread.

Detection of the new SARS-CoV-2 variants of concern B.1.1.7 and B.1.351 in five SARS-CoV-2 rapid antigen tests (RATs), Germany, March 2021

“…Irrespective of whether the virus was a SARS-CoV-2 VOC or not, we generally noticed, in line with previous independent studies [6,7], differences in the LoD of RATs depending on the manufacturer (Table 1). Tests I-IV showed an overall comparable performance and were mostly able to detect the antigen in 1:1,000 dilutions (RNA copies/mL approx.…”

COVID-19 Pandemic: Review of Contemporary and Forthcoming Detection Tools

“…196 A chromatographic digital immunoassay was developed to detect SARS-CoV-2 antigen (ie, nucleocapsid proteins) directly from the nasal swab with 96.6% specificity and 97.6% sensitivity. 197 Another FDA-approved kit based on Microfluidic immunofluorescence assay also detects the viral nucleocapsid antigen; however, it cannot differentiate between SARS-CoV and SARS-CoV-2 antigens. 198…”

Frontline Screening for SARS-CoV-2 Infection at Emergency Department Admission by Third Generation Rapid Antigen Test: Can We Spare RT-qPCR?

“…A number of commercial rapid antigen tests have been licensed to be used in clinical practice [ 22 ], but data on their on-field performance are extremely scarce and heterogeneous. Previous studies have indeed reported a broad spectrum of sensitivity for rapid antigen tests when compared to RT-qPCR (22–100%) [ 10 , 11 , 12 , 14 , 23 , 24 , 25 , 26 ]. Owing to the unavoidable heterogeneity of the field studies on rapid antigen tests, their performance results are frequently lower than those reported by the manufacturers [ 10 , 11 , 12 , 14 , 23 , 24 , 25 , 26 ].…”

“…To the best of our knowledge, this is the first report on the use of a third generation microfluidic immunofluorescence-based antigen test as a frontline screening tool, in association with RT-qPCR, at ED admission in a real-life hospital setting. Even if the 85% sensitivity here reported is far lower than the 97.6% sensitivity described by the manufacturer [ 27 ], the LumiraDX test meets the WHO minimum performance requirements for rapid antigen tests in terms of sensitivity (85% vs. ≥80% recommended), and specificity (97.0% vs. ≥97% recommended) [ 14 ], but falls short of the ECDC 90% sensitivity requirement [ 8 ]. In a recent comparative study evaluating the performances of four different rapid antigen tests against RT-qPCR and cell culture infectivity on 100 samples collected during a random screening within shared living facilities, the LumiraDx assay demonstrated a sensitivity of 50% [ 14 ].…”

“…To complement RT-qPCR testing, many countries have introduced in their diagnostic routine the use of rapid antigen tests [ 1 , 2 , 3 , 4 , 5 , 6 , 7 ], designed to detect the presence of a viral antigen (usually the nucleocapsid, N). Antigen tests are inexpensive and easy to use, even in point-of-care (POC) scenarios, but with the drawback of a diagnostic sensitivity generally lower than that of RT-qPCR, as they provide reliable results only in the presence of high viral loads (≥100,000 copies/mL), and during the first few days since symptom onset [ 8 , 9 , 10 , 11 , 12 , 13 , 14 ]. As a consequence, their correct positioning as frontline screening tests is still controversial.…”