Antigen-based testing but not real-time PCR correlates with SARS-CoV-2 virus culture

Abstract

Individuals can test positive for SARS-CoV-2 by real-time polymerase chain reaction (RT-PCR) after no longer being infectious.1-8 Positive SARS-CoV-2 antigen-based testing exhibits a temporal pattern that corresponds with active, replicating virus and could therefore be a more accurate predictor of an individuals potential to transmit SARS-CoV-2.2,3,9 Using the BD Veritor System for Rapid Detection of SARS-CoV-2 later flow antigen detection test, we demonstrate a higher concordance of antigen-positive test results with the presence of cultured, infectious virus when compared to RT-PCR. When compared to infectious virus isolation, the sensitivity of antigen-based testing is similar to RT-PCR. The correlation between SARS-CoV-2 antigen and SARS-CoV-2 culture represents a significant advancement in determining the risk for potential transmissibility beyond that which can be achieved by detection of SARS-CoV-2 genomic RNA. Coupled with a rapid time-to-result, low cost, and scalability, antigen-based testing should facilitate effective implementation of testing and public health interventions that will better contain COVID-19.

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

“…Although the correlation between viral load and transmissibility is not entirely clear, several studies showed that samples with higher viral loads of ≥6 log 10 RNA copies/mL were likely to correlate with infectivity in cell culture models [ 15 , 25 , 26 , 27 , 28 ]. We, and others, showed that Ag-RDTs, although less sensitive, align better with cell culture-based testing for infectivity than rRT-PCRs [ 14 , 25 , 29 , 30 , 31 ].…”

Evaluation of a rapid antigen test (Panbio™ COVID-19 Ag rapid test device) for SARS-CoV-2 detection in asymptomatic close contacts of COVID-19 patients

“…RAD tests are simple to carry out and return results within a short time, thus being well-suited for point-of-care testing (POCT). Moreover, two recently evaluated RAD assays (BD Veritor System and the Panbio™ COVID-19 Ag Rapid Test Device) may be used as a proxy for SARS-CoV-2 cultured from respiratory tract specimens, thus allowing reasonably accurate prediction of contagiousness [ 2 , 3 ]; yet this assumption awaits further validation in larger cohorts. The possibility of using RAD tests to identify SARS-CoV-2-infected asymptomatic contacts of COVID-19 patients is appealing, as it could effectively contribute to minimize community SARS-CoV-2 spread through early detection of highly infectious individuals [ 1 ], yet little is known about how RAD tests perform in this population group [ [4] , [5] , [6] ].…”

COVID-19 testing: One size does not fit all

“…COVID-19 tests include molecular tests such as qPCR, isothermal amplification, and CRISPR, as well as antigen tests that detect SARS-CoV-2 proteins directly. Although rapid antigen tests have lower analytical sensitivity (i.e., require greater amounts of virus material to turn positive) than qPCR-based tests, their ability to detect infectious individuals with culturable virus is as high as for qPCR (3). Specificity (i.e., correctly identifying those not infected with SARS-CoV-2) of antigen tests achieves comparable results to molecular tests (4).…”