key: cord-0770963-c5g2xq2e
authors: Eleftheriou, Irini; Dasoula, Foteini; Dimopoulou, Dimitra; Lebessi, Evangelia; Serafi, Eftihia; Spyridis, Nikos; Tsolia, Maria
title: Real‐life evaluation of a COVID‐19 rapid antigen detection test in hospitalized children
date: 2021-07-01
journal: J Med Virol
DOI: 10.1002/jmv.27149
sha: 21cc5b9fb0df42fd9197ab8ac46a7c8cd22fb400
doc_id: 770963
cord_uid: c5g2xq2e

Rapid antigen detection (RAD) tests for the detection of SARS‐CoV‐2 are simpler, faster, and less expensive than the reverse‐transcription polymerase chain reaction (RT‐PCR) that is currently considered the gold standard for the diagnosis of coronavirus disease 2019 (COVID‐19). The objective of this study was to determine the performance of the PANBIO COVID‐19 Ag RAD (Abbott) test, a lateral flow immunoassay that detects the nucleocapsid protein, using as a reference RT‐PCR method the Cobas®8800 System (Roche Diagnostics). This prospective study was conducted in a tertiary Children's Hospital and included individuals aged ≤16 years with COVID‐19‐related symptoms or epidemiological criteria for COVID‐19. Two nasopharyngeal samples were collected to perform the PANBIO RAD test and RT‐PCR. Of 744 children included, 51 (6.86%) had a positive RT‐PCR result. The RAD test detected 42 of 51 PCR‐positive children while there were no false‐positive results. The overall sensitivity and specificity were 82.35% (95% CI, 71.9%–92.8%) and 100%, respectively. Sensitivity was >95% in symptomatic children. The assay performed poorly in asymptomatically infected children. In agreement with previous studies in adults, the PANBIO RAD test can be useful in screening for COVID‐19 in children admitted with symptoms suggestive of the disease, especially in the first days of the illness.

The ongoing severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) pandemic challenges public health systems worldwide. Rapid and accurate diagnosis of coronavirus disease 2019 (COVID-19) is essential to facilitate treatment, reduce the spread of disease, protect healthcare workers and ensure the optimal use of personal protective equipment.

Reverse-transcription quantitative polymerase chain reaction (RT-qPCR) in nasopharyngeal samples is the currently recommended method to diagnose acute infection due to its favorable performance characteristics.

However, molecular techniques require trained personnel and specialized equipment and the turnaround time may be considerably longer. In contrast, rapid antigen detection (RAD) tests are considered less sensitive, but they have the advantages of simple operation, short turnaround time, and low cost. 1, 2 To date, several RAD tests have been evaluated but to our knowledge data on children are scarce.

The study was conducted in "P. and A. Kyriakou" Children's Hospital, Athens, Greece.

We evaluated the PANBIO COVID-19 Ag RAD test (Abbott-Chicago) in children ≤16 years of age admitted to a tertiary Children's hospital in Athens during the second and third pandemic waves using as a reference RT-PCR method, the Cobas®8800 System (Roche Diagnostics).

This prospective study was conducted between September 25th, 2020 to February 28th, 2021 in the second largest pediatric hospital of the country and a reference center for children with COVID-19.

Children admitted to our hospital and tested for SARS-CoV-2 using both RAD test and RT-PCR were included. According to local protocol, children were tested either because they had symptoms suggestive of COVID-19 or they were considered at high risk of infection based on regional epidemiological data such as belonging to minority populations or originating from high prevalence regions. On admission, two nasopharyngeal samples were simultaneously collected, each one from a separate nostril. Oral informed consent was obtained from the patients' parents for double sampling. One of the samples was taken with the swab provided by the PANBIO RAD test and the other one with a swab that was then embedded in a universal transport medium for RT-PCR (Copan flocked swabs with UTM™, Universal Transport Medium). The PANBIO COVID-19 Ag RAD test is a lateral flow immunoassay that detects the nucleocapsid protein providing results in 15 min. The Cobas®8800 System detects ORF1 a/b, a nonstructural region unique to SARS-CoV-2, and the structural protein envelope E-gene that is found in all the members of Sarbecovirus subgenus. The turnaround time of the molecular assay performed at a National Reference Centre was 6-12 h. All RAD tests were performed immediately at the bedside, according to the manufacturer's instructions. Samples used for molecular testing were transferred to the National Reference Centre by three daily shipments. The lab personnel who handled these samples was blinded to the results of the RAD test. Both tests' results, the symptoms and number of days since their onset, Cycle threshold (C t ) values for RT-PCR, and demographic data were prospectively recorded for all participants. The study was approved by the Ethics Committee of the "P. and A. Kyriakou" Children's Hospital (EC 18155/02.11.2020).

The sensitivity and specificity of the PANBIO RAD test, with 95% confidence intervals (CI), were calculated using the RT-PCR results as the standard. Sensitivity was calculated for all patients and for specific groups of patients according to the presence of symptoms and RT-PCR C t values. The level of agreement between the tests was estimated using Cohen's κ index. Statistical analyses were performed using the free, open-source software environment R.

A total of 744 children were included; 57.9% (431 of 744) were male. In this study, the PANBIO RAD test had a good clinical performance, with an overall sensitivity of 82.35% and a specificity of 100%. According to WHO guidelines, sensitivity ≥80% and specificity ≥of 97% are required for these tests compared to the RT-PCR assay. 1 The results of the current study agree with previously reported findings in adults. 6 However, previously conducted studies in children have demonstrated lower performance of antigen tests. 7 In a primary care setting, the PANBIO RAD test had a significantly higher sensitivity in adults (82.6%) compared to pediatric patients (62.5%). 8 Masiá et al. 9 found that younger age was independently associated with the poorest performance. Researchers claim that there are difficulties in collecting nasopharyngeal swabs in young children, dating of symptoms onset may be more inaccurate or C t values may be lower in children compared to adults. However, the first of the above-mentioned studies included 85 children while the median age of participants in the second study was 40.6 years (23.0-55.6). In a retrospective, multicenter study that included more than 1600 symptomatic children attending the ED, the overall sensitivity of the PANBIO RAD test was 45.4%. 10 By contrast, in a prospective multicenter study conducted in ten university hospitals, the RAD assay was positive in all six out of 58 pediatric patients who had a positive RT-PCR result. 11 However, the small number of cases in this study does not permit any robust conclusions. Given that viral loads do not differ significantly between children and adults, 12 we optimal sensitivity is required for accurate diagnosis and for the prevention of SARS-CoV-2 spread. 14 However, the assay performs well in symptomatic children hospitalized with COVID-19 and it has a much shorter turnaround time compared to RT-PCR. Therefore, it can be useful in screening for COVID-19 in children admitted with symptoms suggestive of the disease, permitting their early diagnosis, isolation, and management, especially in the first days of the illness.

The authors declare that there are no conflict of interests.

The data that support the findings of this study are available from the corresponding author upon reasonable request. 

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Real-life evaluation of a COVID-19 rapid antigen detection test in hospitalized children