key: cord-1040169-7erudqaj
authors: Quentin, Ollier; Sylvie, Pillet; Olivier, Mory; Julie, Gagnaire; Charlotte, Thuiller; Nadine, Annino; Amandine, Gagneux-Brunon; Elisabeth, Botelho-Nevers; Thomas, Bourlet; Bruno, Pozzetto; Aymeric, Cantais
title: Prospective evaluation of the point-of-care use of a rapid antigenic SARS-CoV-2 immunochromatographic test in a pediatric emergency department
date: 2022-01-20
journal: Clin Microbiol Infect
DOI: 10.1016/j.cmi.2021.12.019
sha: b482a60c7f3a383e4fd6f1b10d388d318bcac360
doc_id: 1040169
cord_uid: 7erudqaj

OBJECTIVES: This study aimed at evaluating the immunochromatographic COVID19Speed-Antigen Test (BioSpeedia, France) as antigen point-of-care test (AgPOCT) to detect SARS-CoV-2 infection in the paediatric emergency department of the University Hospital of Saint-Etienne, France. METHODS: Between January 15(th) and May 28(th) 2021, every child presenting a respiratory symptomatology compatible with Covid-19 (symptomatic group) or requiring hospitalization for any reason (asymptomatic group) was included prospectively and received a nasopharyngeal aspiration (NPA) to carry out both AgPOCT and RT-qPCR test, the latter being used as gold standard, for the diagnosis of SARS-CoV-2 infection. RESULTS: Among the 1009 enrolled children, we obtained a result by both techniques for 990 of them: 33 (3.3%) were positive by AgPOCT and 46 (4.6%) by RT-qPCR. The overall sensitivity and specificity of the AgPOCT were 69.6% (CI95% 54.3-82.3) and 99.9% (CI95% 99.4-100), respectively, by comparison to RT-qPCR. Its sensitivity was increased to 82.9% (CI95% 66.4-93.4) in symptomatic children. The mean cycle threshold (Ct) value was significantly lower in positive samples for AgPOCT than in negative ones, in the overall population and in both symptomatic and asymptomatic groups. CONCLUSIONS: The use of the COVID19Speed-Antigen Test at bedside in the emergency room provides satisfactory performances for diagnosing SARS-CoV-2 infection in symptomatic children.

Objectives 26

This study aimed at evaluating the immunochromatographic COVID19Speed-Antigen Test 27 (BioSpeedia, France) as antigen point-of-care test (AgPOCT) to detect SARS-CoV-2 infection in the 28 paediatric emergency department of the University Hospital of Saint-Etienne, France. 29

Between January 15 th and May 28 th 2021, every child presenting a respiratory symptomatology 31 compatible with Covid-19 (symptomatic group) or requiring hospitalization for any reason 32 (asymptomatic group) was included prospectively and received a nasopharyngeal aspiration (NPA) to 33 carry out both AgPOCT and RT-qPCR test, the latter being used as gold standard, for the diagnosis of 34

Results 36

Among the 1009 enrolled children, we obtained a result by both techniques for 990 of them: 33 37 has been widely recommended to undertake interventions based on case finding and contact tracing. 50

In symptomatic patients, the spreading of infectious virus primarily occurs before the time of 51 symptom onset. RT-qPCR testing performed on a nasopharyngeal sample is the gold standard for 52 SARS-CoV-2 detection (1); it allows a semi-quantitative estimation of viral load by the cycle threshold 53 (Ct) value. Nevertheless, this kind of molecular assay requires trained personnel, sophisticated 54 laboratory equipment, and logistical planning. They are not fully adapted to the rapid screening of 55 SARS-CoV-2 infected patients consulting at the emergency department (2). Consequently, delays in 56 obtaining RT-qPCR results can rarely be shortened and can even be slowed down by the increasing 57 demand for tests (3), whereas quickness of results is a crucial factor to control the viral transmission . 58

By the mid of 2020, in parallel to rapid molecular tests based on different amplification technologies 59 as LAMP or RT-PCR, antigen point-of-care tests (AgPOCT) appeared as an exciting and cost-effective 60 alternative for rapid SARS-CoV-2 diagnosis. Although their analytical performances are inferior to 61 those of RT-qPCR (4), they allow bedside testing, giving a piece of essential information within a few 62 minutes. Despite the availability of a myriad of commercial SARS-CoV-2 AgPOCT, each has to be 63 carefully evaluated in field conditions. Several evaluations of antigen tests have been published, but 64 most of these studies were conducted either in only adults (4-8) or in both adults and children 65 (9,10). This could be explained by the fact that children are considered far less important drivers of 66 Covid-19 than adults (11-13). Nevertheless, they can be part of the transmission chain (14), as seen 67 by the increasing number of positive tests in the pupil population since the schools' reopening 68 around the world. To the best of our knowledge, the accuracy of only two commercial AgPOCT kits 69 has been evaluated in the pediatric population (15-17). Patients between 0 and 15 years old and those older who had still regular pediatric follow-ups were 82 eligible. Each child for whom an AgPOCT test was realized was included prospectively. The indication 83 to perform a test in our centre was the presence of symptoms evocative of Covid-19, the notion of 84 contact with an infected person, and/or hospitalization. Institutionally, each hospitalized child was 85 indeed systematically tested for SARS-CoV-2 infection before entering the hospital ward, whatever 86 the reason for hospitalization. 87

Two categories of patients were defined retrospectively. The "symptomatic group" included all 88 patients presenting a clinical picture compatible with Covid-19, as described for children by 89 Mansourian et al. (18) , including the following symptoms: fever, cough, vomiting, diarrhoea, sore 90 throat, and dyspnea. The "asymptomatic group" gathered all the other patients whose symptoms 91

were not considered as clinically evocative of The data collected at enrolment are shown in Table 1 . 93

Procedures 95

According to the current procedure of the pediatric emergency department (19), a single 96 nasopharyngeal aspirate (NPA) was performed for each child by a nurse using an atraumatic flexible 97 hose. Following NPA sampling, the sterile swab provided in the AgPOCT kit was immersed in the 98 sample and rolled three times before being introduced into the reagent tube. The AgPOCT was then 99 the remaining of the NPA sample was sent to the hospital laboratory for RT-qPCR analysis (r-gene, 101 bioMérieux, France) on an ABI7500 fast thermocycler (Thermofisher, France) after extraction of total 102 nucleic acids using the NUCLISENS eMAG platform (bioMérieux). 103

During the outbreak of respiratory syncytial virus (RSV), which started on 19 March 2021 (20) and 104 was still ongoing in August 2021, an AgPOCT (Veritor) was used 24/7 at the pediatric emergency 105 room in children exhibiting a clinical picture of bronchiolitis, as previously described (19). As no 106 influenza virus circulated during the study period, the AgPOCT for flu diagnosis was not used. 107

According to the judgment of the physician in charge at inclusion, some patients were also tested by 108 the same NPA with a Luminex®-based multiplex PCR assay ( Table 1 ). The most frequently registered symptoms were fever (n=343, 69.7%), 167 rhinorrhea (n=320, 65.2%) and cough (n=314, 64.0%). Of note, no child presented a severe form of 168

Covid-19. Thirty-five (7.3%) symptomatic patients were positive for SARS-CoV-2 by RT-qPCR (Table 2) . 169

The analysis disclosed a sensitivity of 82.9% (95%CI 66.4-93.4) and a specificity of 99.8% (95%CI 98.7-170 100) in this group (Table 3) . As shown in Figure 1B , the sensitivity of the AgPOCT was closely related 171 to the Ct value of the RT-qPCR assay. 172

Among the 516 (51.1%) asymptomatic participants at the time of sampling, 3 (0.6%) were positive by 175

AgPOCT and 11 (2.1%) by RT-qPCR ( Figure 1B) , with significantly higher Ct value than that found in 176 symptomatic participants (Table 2) . With a sensitivity of only 27.3% and a specificity of 100%, false-177 negative AgPOCT mainly happened in the asymptomatic group (Table 3) disease. The better sensitivity of the AgPOCT used in this study compared to previous data using tests 200 based on the same technology could be due in part to the good performance of this particular assay, 201 but also to the fact that the alpha variant of SARS-CoV-2 circulated preferentially during the study 202 period since this variant was shown to exhibit higher viral loads (31). 203

Our study has also some limitations. The number of positive samples was limited by the low 204 prevalence of SARS-CoV-2 infection during the study period, which reduces the statistical power of 205 the analysis. Second, we analyzed a single commercial rapid test; despite the satisfactory 206 performances of the COVID19Speed-Antigen Test, our conclusions cannot be extended to other 207 commercial brands, which imply that the performances of an antigenic test must be assessed very 208 carefully before being used as POC test at bedside. Third, our study is monocentric by construction, 209 which raises methodological weaknesses. Finally, the WHO international standard was not used to 210 convert the Ct values of the PCR assay in international units per ml, as exemplified in (27). 211

In conclusion, our results assess the acceptable sensitivity and specificity of the COVID19Speed-212

Antigen Test in symptomatic children. Consequently, this AgPOCT could be used in efforts to limit the 213 viral spread in pediatric emergency settings. In our institution, the AgPOCT is presently used in all J o u r n a l P r e -p r o o f J o u r n a l P r e -p r o o f 

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