








key: cord-343800-nbydaoac
authors: Cerutti, Francesco; Burdino, Elisa; Milia, Maria Grazia; Allice, Tiziano; Gregori, Gabriella; Bruzzone, Bianca; Ghisetti, Valeria
title: Urgent need of rapid tests for SARS CoV-2 antigen detection: evaluation of the SD-Biosensor antigen test for SARS-CoV-2
date: 2020-09-29
journal: J Clin Virol
DOI: 10.1016/j.jcv.2020.104654
sha: 
doc_id: 343800
cord_uid: nbydaoac

At the time of writing, FIND has listed four CE-marked SARSCoV-2 antigen tests. We evaluated the recently CE-approved rapid POCT SD-Biosensor for SARS-CoV-2 nucleoprotein detection in nasopharyngeal secretions from 330 patients admitted to the Emergency Room for a suspect of COVID-19 and travelers returning home from high risk countries. Sensitivity, specificity, accuracy, negative and predictive values were consistent with the use of the test to mass-screening for SARS-CoV-2 surveillance.

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that demands rapid and cost-efficient approaches. The currently gold standard for the detection of SARS-CoV-2 relies on viral RNA amplification by real-time RT-PCR (RT-PCR) and requires few hours before results release [1] . The pandemic highlighted the limits of production and trade for molecular tests as we are facing a worldwide shortage of reagents. Point-of-care diagnostic tests (POCTs) for detecting viral antigens in clinical samples would be very helpful for the diagnosis of COVID-19 [2] either as mass-screening or first aid tests at the emergency room. At the time of writing, the Foundation for Innovative New Diagnostics (https://www.finddx.org/) has listed four CE-marked rapid SARS-CoV-2 antigen tests, which are primarily lateral flow immunochromatographic assays from nasopharyngeal swab (NP) with result reporting in less than 30 minutes. The evaluation of these tests by the scientific community, even if limited, outlines the major concern of false-negative results due to low viral loads. In fact, recently published works from different countries evaluating commercial and in-house POCTs for SARS-COV-2 showed a concordant high level of specificity (from 99.5 to 100%), but a wide range of sensitivity (30% -93.9% [3, 4] . Therefore, great efforts for the implementation of antigen test performance are currently on-going.

To evaluate a recently CE-approved POCT, the STANDARD Q COVID-19 Ag (SD-Biosensor, RELAB, I), for the detection of SARS CoV-2 nucleoprotein in NP swabs in comparison with the gold standard RT-PCR. POCT performances were studied in terms of sensitivity, specificity, and negative and predictive values to assess the contribution of this test to massscreening for COVID-19.

The STANDARD Q COVID-19 Ag (R-Ag) was applied to 330 patients of two different populations from the phase-1 and -3 of the pandemic according to the Italian Government measures 

Detection rates of SARS CoV-2 by R-Ag and RT-PCR were 23.3% (77/330) and 33%

(109/330), respectively; no false positive with R-Ag were observed ( According to different mean Ct classes (≤25, 25-28, 28-30, 30-35, >35) the detection rate of R-Ag was 100% for samples with a Ct <28 and decreased to 38.5%, 26.7%, and 9.1% in the other ranks. Figure 2 shows the ROC curve for R-Ag to estimate the Ct threshold value for R-Ag to detect a positive swab (equal to 27.7). In Table 2 

To control COVID-19 pandemic, improvement of SARS CoV-2 diagnosis with easy, rapid and cost-efficient approaches is urgently required. POCTs for the detection of SARS-CoV-2 J o u r n a l P r e -p r o o f antigens are quite promising; however, the principal concerns are the false-negative rate due to low viral loads [3] [4] [5] [6] [7] [8] .

The STANDARD Q COVID-19 Ag identified 70.6% of RT-PCR positive sample, respectively, with no false positive results (100% of specificity). Using the Ct value by RT-PCR as a proxy for viral load, R-Ag-positive samples had a significantly lower Ct than that of R-Agnegative samples; the majority of discordant RT-PCR-positive/R-Ag-negative samples reported negative results when cell-cultured. Therefore, R-Ag false negative results were found in samples with a low viral load, consistent with low viable virus and low infectiousness [9, 10] . A major limit of our study was that the test was assessed in suboptimal conditions using UTM samples instead of on-site NP swabs.

The clinical performance of POCTs largely depends on the circumstances in which they are used, and the appropriate setting should be identified. In agreement with recently published works, our data confirm that this POCT is effective during the acute/recent phase of the disease within a few days after symptoms onset when the viral load in the upper respiratory tract is at its peak [3] [4] [5] 11 ]. The adoption of POCT for SARS CoV-2 testing is certainly more suitable in point of care centers for mass screening where the prevalence of COVID-19 is much lower and the pre-test probability of not having the disease is higher than that in the patients admitted to the emergency room were the pre-test probability of having COVID-19 is significantly higher and false negative results are relevant for the correct management of patients.

The main advantages of POCTs for antigen testing are rapidity, easy of interpretation, limited technical skill and infrastructure required, and this continues to make them worth pursuing.

Lastly, the adoption of POCTs in mass screening testing could decrease the burden on virology laboratories that have been overwhelmed during the last COVID-19 pandemics, and the shortage of reagent they are facing. 

We thank RELAb for the donation of the STANDARD Q COVID-19 SD-Biosensor kits to pursue the study. No other specific grant from public funding agencies was received.

The authors declare no competing interest. 

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