key: cord-288425-po35m6d9
authors: Albert, Eliseo; Torres, Ignacio; Bueno, Felipe; Huntley, Dixie; Molla, Estefanía; Fernández-Fuentes, Miguel Ángel; Martínez, Mireia; Poujois, Sandrine; Forqué, Lorena; Valdivia, Arantxa; Solano de la Asunción, Carlos; Ferrer, Josep; Colomina, Javier; Navarro, David
title: Field evaluation of a rapid antigen test (Panbio™ COVID-19 Ag Rapid Test Device) for COVID-19 diagnosis in primary healthcare centers
date: 2020-11-13
journal: Clin Microbiol Infect
DOI: 10.1016/j.cmi.2020.11.004
sha: 
doc_id: 288425
cord_uid: po35m6d9

OBJECTIVES: To our knowledge no previous study has assessed the performance of a rapid antigen diagnostic immunoassay (RAD) conducted at the point of care (POC). We evaluated the Panbio™ COVID-19 Ag Rapid Test Device for COVID-19 diagnosis in symptomatic patients (n=412) attended in primary healthcare centers. METHODS: RAD was performed immediately after sampling following the manufacturer’s instructions (reading at 15 min.). RT-PCRs were carried out within 24 h. of specimen collection. Samples displaying discordant results were processed for culture in Vero E6 cells. Presence of SARS-CoV-2 in cell cultures was confirmed by RT-PCR. RESULTS: Out of 412 patients, 43 (10.4%) tested positive by RT-PCR and RAD and 358 (86.9%) negative by both methods, showing discordant results (RT-PCR+/RAD-) in 11 patients (2.7%). Overall specificity and sensitivity of rapid antigen detection (RAD) was 100% (95% CI, 98.7-100%), and 79.6% (95% CI, 67.-88.8%), respectively, taking RT-PCR as the reference. Overall RAD negative predictive value for an estimated prevalence of 5% and 10% was 99% (95% CI, 97.4-99.6%) and 97.9% (95% CI, 95.9-98.9), respectively. SARS-CoV-2 could not be cultured from specimens yielding RT-PCR+/RAD-results (n=11). CONCLUSION: The Panbio™ COVID-19 Ag Rapid Test Device performed well as a POCT for early diagnosis of COVID-19 in primary healthcare centers. More crucially, the data suggested that patients with RT-PCR-proven COVID-19 testing negative by RAD are unlikely to be infectious.

Objectives: To our knowledge no previous study has assessed the performance of a 24 rapid antigen diagnostic immunoassay (RAD) conducted at the point of care (POC). We 25 evaluated the Panbio™ COVID-19 Ag Rapid Test Device for COVID-19 diagnosis in 26 symptomatic patients (n=412) attended in primary healthcare centers. Table 1 ). Concordance between the two methods was good (κ, Table 2 ).

Overall RAD negative predictive value for an estimated prevalence of 5% and 10% (the 106 incidence of COVID-19 in our Health Department during the study period was within 107 that range), was 99% (95% CI, 97.4-99.6%) and 97.9% (95% CI, 95.9-98.9), 108 respectively.

RT-PCR C T values were significantly higher and SARS-COV-2 RNA loads 110 significantly lower (P <0.001) in RT-PCR+/RAD-than in RT-PCR+/RAD+ specimens 111 ( Figures 1B and 1C) . ROC curve analyses indicated that RT-PCR C T <25 and SARS-range, 1-6 days) patients.

All 11 specimens yielding discordant RT-PCR/RAD results tested negative by culture, 120 whereas SARS-CoV-2 could be recovered from all 3 specimens returning RT-121 PCR+/RAD+ results (C T : 4, 14 and 16). Nevertheless, the overall sensitivity for the RAD assay reported herein was much closer 134 to that (86.5%) found by Linares and colleagues [3] . Sensitivity of SARS-CoV-2 RAD 135 assays has been reported to vary between 45%-97% [3-7], yet direct comparison 136 between studies is hampered by marked dissimilarities in patient clinical characteristics 137 and age, testing sites, type of specimen processed, and time to testing, among others.

Interestingly, sensitivity was higher in adults than in pediatric patients. Previous studies 139 found no age-related differences in SARS-CoV-2 RNA load in the upper respiratory tract [8] . Although speculative, dating of symptoms onset could have been more 141 inaccurate in children than in adults.

In a setting like ours with an incidence of COVID-19 ranging between 5% and 10% at 143 the time of study, the RAD NPV was 99% (95% CI, 97.4-99.6%) and 97.9% (95% CI, 144 95.9-98.9), respectively.

Out of 54 RT-PCR positive specimens, 11 tested negative by RAD. In line with 146 previous reports [2-4], SARS-CoV-2 RNA load was significantly higher in RT-PCR+/ 147 RAD+ specimens than in RT-PCR+/ RAD-samples. In our setting, specimens with RT-148 PCR C T >25 (equivalent to SARS-CoV-2 RNA loads < 5.9 log 10 copies/ml) returned 149 discordant RAD/RT-PCR results.

An important observation of our study was that SARS-CoV-2 could not be cultured 151 from RT-PCR+ (C T >25)/RAD-specimens. Along these lines, Pekosz and colleagues [2] 152 found 1 out of 27 RAD-/culture + specimens, using a highly sensitive cell culture 153 system (VeroE6 TMPRSS2). The SARS-CoV-2 RNA load threshold associated with 154 culture positivity herein (> 5.9 log 10 copies/ml) was remarkably close to other 155 previously published results (around 10 6 copies/ml) [2, [9] [10] [11] University Hospital for their unwavering commitment in the fight against COVID-19. 179 We would also like to thank María José Beltrán, Pilar Botija and Ana Sanmartín for 180 assistance in organizing RAD testing in primary healthcare centers.

This work received no public or private funds. Our group has received private funds for 

Antigen-based testing but not real-time PCR correlates with SARS-CoV-2 virus 198 culture

Panbio antigen rapid test is reliable to diagnose SARS-CoV-2 202 infection in the first 7 days after the onset of symptoms

Low performance of rapid antigen detection test as 210 frontline testing for COVID-19 diagnosis

Evaluation of a Rapid Diagnostic Assay for Detection 213 of SARS-CoV-2 Antigen in Nasopharyngeal Swabs

Evaluation of 216 rapid antigen test for detection of SARS-CoV-2 virus

CoV-2 viral load in the upper respiratory tract of children and adults with early 220 acute COVID-19

Virological assessment of hospitalized patients with COVID-2019

Based Virus Isolation To Evaluate Potential Infectivity of Clinical Specimens 226 Tested for COVID-19