key: cord-0888231-hclqsba1 authors: Cassuto, Nino Guy; Gravier, Anne; Colin, Mathilda; Theillay, Aurelie; Pires‐Roteira, Daniela; Pallay, Sandra; Serreau, Raphael; Hocqueloux, Laurent; Prazuck, Thierry title: Evaluation of a SARS‐CoV‐2 antigen‐detecting rapid diagnostic test as a self‐test: Diagnostic performance and usability date: 2021-08-26 journal: J Med Virol DOI: 10.1002/jmv.27249 sha: fb88037cad24edad337012bd82cfc2e8c5ffb13f doc_id: 888231 cord_uid: hclqsba1 To control the spread of the coronavirus disease 2019 (COVID‐19) epidemics, it is necessary to have easy‐to‐use, reliable diagnostic tests available. The nasopharyngeal sampling method being often uncomfortable, nasal sampling could prove to be a viable alternative to the reference sampling method. We performed a multicentre, prospective validation study of the COVID‐VIRO® test, using a nasal swab sampling method, in a point‐of‐care setting. In addition, we performed a multicentre, prospective, and usability study to validate the use of the rapid antigen nasal diagnostic test by laypersons. In March 2021, 239 asymptomatic and symptomatic patients were included in the validation study. Compared with reverse‐transcription polymerase chain reaction on nasopharyngeal samples, the sensitivity and specificity of the COVID‐VIRO® Antigen test combined with a nasal sampling method were evaluated as 96.88% and 100%, respectively. A total of 101 individuals were included in the usability study. Among these, 99% of the participants rated the instructions material as good, 98% of the subjects executed the test procedure well, and 98% of the participants were able to correctly interpret the test results. This study validates the relevance of COVID‐VIRO® as a diagnostic tool from nasal specimens as well as its usability in the general population. COVID‐VIRO® diagnostic performances and ease of use make it suitable for widespread utilization. disease are fever, cough, and fatigue, but other symptoms include headache, sore throat, and even acute respiratory distress syndrome, leading to respiratory failure. In an effort to control the spread of the epidemic, it is crucial to have highly sensitive and specific tests available. Indeed these tests are key to identify and manage COVID-19 cases and implement control measures. As of now, the gold standard for the detection of SARS-CoV-2 infection is the reverse-transcription polymerase chain reaction (RT-PCR) method based on the molecular detection of the virus genetic material from a nasopharyngeal sample. 3 This detection is highly sensitive and reliable but requires very specific and somewhat expensive material and equipment. Moreover, nasopharyngeal sampling requires training to be performed in a safe and reliable manner and the results can sometimes only be obtained after several days, depending on the laboratory. Finally, although nasopharyngeal sampling is generally safe, this procedure is not risk-free, especially when performed in a repetitive and intensive manner. 4 Indeed, in some rare instances, cerebrospinal leak and meningitis have been documented. [5] [6] [7] Saliva sampling has been recently approved and proved to be as reliable and simpler than nasopharyngeal sampling but still does not provide a quick result. 8 To have rapid, reliable, and simple tests, lateral-flow immunoassays have been recently developed to detect the presence of the virus antigens from nasopharyngeal samples. These SARS-CoV-2 specific antigen assays rapid antigen diagnostic test (RADT) are a simple and fast alternative to the RT-PCR method and are available in pharmacies. They take around 15 min to provide a result but because of the sampling method, they are not convenient for an at-home testing strategy. From a public health perspective, self-tests can usefully complement point-of-care tests by allowing more globally scaled testing. If reliable, self-test allows individuals to obtain a quick result, thereby supporting the early detection and isolation of COVID-19 cases. 9 These tools can be essential to large scale distribution of COVID-19 diagnostic tests, and as such, the FDA has already approved several antigen home tests and the French health authority (Haute autorité de Santé [HAS]) has defined the minimum performance requirements for these tests with an emphasis on the necessity of conducting real-life studies. 10-12 The diagnostic performance of COVID-VIRO ® (AAZ, LMB), an antigenbased rapid detection test, has already been assessed on nasopharyngeal samples performed by trained professionals. 13 The objective of this study was to evaluate the diagnostic performance of COVID-VIRO ® using a nasal swab sampling method when compared with the reference method, as well as its usability as a self-test adapted for the general population. The study was evaluated and approved by the French ethics committee (Comité de Protection des Personnes Nord-Ouest IV) in October 2020 and was notified to the French data protection authority. This study was conducted in accordance with the Declaration of Helsinki. This implies that all participants provided written informed consent before undergoing any study-specific procedure. Two different study settings were used, one for the performance study and one for the usability/practicability study: The performance study was set in the two COVID units of the Centre Hospitalier Régional d'Orléans: La Madeleine Hospital and La Source Hospital. The inclusion criteria were the following: adults volunteers (>18 years old) with mild to moderate symptoms lasting less than 7 days and not requiring immediate hospitalization (headache, fatigue, fever, sore throat, aches and pains, loss of smell and taste, etc.). The noninclusion criteria were: hospitalized patients, symptomatic patients with symptom duration more than 7 days, asymptomatic patients, or asymptomatic contact with a known case. Regarding the usability study, the adult volunteers who participated were patients of a medical analysis laboratory (Drouot laboratory) as well as volunteer patients consulting in our infectious diseases department or hospitalized in our COVID unit (Orléans Regional Hospital). No specific inclusion/noninclusion criteria were applied. The RT-PCR test for SARS-CoV-2 was performed in the virology unit of the CHR Orléans, France. Nucleic acid extraction was performed with an automated sample preparation system MGISP- Upon arrival at one of the two study centers, patients were registered for nasopharyngeal RT-PCR testing. Eligible patients were informed about the study. After consent to participate, the trained nurse performed the COVID-VIRO ® nasal swab test and recorded the test result on the previously filled-in collection form without communicating it to the patient. Then, a nasopharyngeal swab is taken by the nurse for the RT-PCR test by the hospital laboratory. The RT-PCR test was performed using the TaqPath V2 COVID-19 Multiplex RT-PCR from Thermo Fisher Scientific including a variant screening. The RT-PCR result was then communicated to the patient within 24 h and recorded in the patient's file. Table 1 ). The person performing the test was supervised by an observer (laboratory staff, nurse, or doctor) who gave a posteriori assessment of the performance of the various steps by filling in an evaluation form for each participant (Table 1) . Confidence intervals for sensitivity were obtained with the Wilson score method. Populations were described in terms of absolute number and percentage. In addition to the performance assessment, we performed a usability study following the FDA recommendations. 19 The participant was asked to read or watch the test instructions and perform all the procedures while being supervised, to assess whether the participant was able to correctly perform the test on his/her own and interpret it accurately. Due to the setting of this trial (private and public la- The results showed that the COVID-VIRO ® test is very practicable as only a small fraction of the participants were not able to obtain valid and interpretable results. Moreover, almost all the participants were able to perform the test procedures without requesting the supervisor's assistance and their execution was highly rated by the supervisors. In terms of satisfaction, when asked their opinion about COVID-VIRO ® 's ease of use, all the participants declared that the sample collection or the subsequent testing procedures were easy or very easy to perform. Nevertheless, a very small fraction of the participants found the reading and the interpretation steps somewhat difficult. This, however, did not affect their capacity to correctly interpret the test results with one notable exception. Taken together, these results show that the COVID-VIRO ® test is highly adapted for use by a layperson. To our knowledge, this is the first usability study of a nasal rapid antigen test combining an easy sampling method (nasal swab) with a highly accurate diagnostic test that should allow the health authorities to consider wider use of this test (children, iterative screening, …) by health professionals as well as its adaptation in self-test version for use by laymen. Nasal tests are of particular interest because they can mitigate the risks and adverse effects of nasopharyngeal tests (discomfort, pain, deeper lesions, etc.) and are well suited for situations when no trained professional is available such as social gatherings, offices, and schools. However, it is important to consider that, as pointed out by the European Medicine Agency, the use of RADTs by the general population raises the concern of underreporting. Therefore, in the interest of the global effort to contain the spread of the virus, it could be necessary to include a set of instructions encouraging test users to report any positive results. 9 World Health Organization. the media briefing on COVID-19 The epidemiology and pathogenesis of coronavirus disease (COVID-19) outbreak Severe acute respiratory syndrome-related coronavirus: The species and its viruses -a statement of the Coronavirus Study Group COVID-19: which samples for which tests? Cerebrospinal fluid leak after nasal swab testing for coronavirus disease 2019 Meningitis due to cerebrospinal fluid leak after nasal swab testing for COVID-19 Complications of nasal and pharyngeal swabs: a relevant challenge of the COVID-19 pandemic? New COVID-19 saliva-based test: how good is it compared with the current nasopharyngeal or throat swab test? Food and Drug Administration. FDA authorizes antigen test as first overthe-counter fully at-home diagnostic test for COVID-19 FDA continues to advance over-the counter and other screening test development COVID-19: quelle place pour les tests antigéniques nasaux dans la stratégie de dépistage? High performance of a novel antigen detection test on nasopharyngeal specimens for diagnosing SARS-CoV-2 infection relatif à l'interprétation de la valeur de Ct (estimation de la charge virale) obtenue en cas de RT-PCR SARS-CoV-2 positive -Version 4 du 14/ 01/2021Avis du 25 septembre 2020 de la Société Française de Microbiologie (SFM) relatif à l'interprétation de la valeur de Ct (estimation de la charge virale) obtenue en cas de RT-PCR SARS-CoV-2 positive sur les prélèvements cliniques réalisés à des fins diagnostiques ou de dépistage World Health Organization. SARS-CoV-2 antigen-detecting rapid diagnostic tests: an implementation guide Head-to-head comparison of SARS-CoV-2 antigen-detecting rapid test with self-collected nasal swab versus professional-collected nasopharyngeal swab COVID-19: rapid antigen detection for SARS-CoV-2 by lateral flow assay: a national systematic evaluation for mass-testing. medRxiv Self-testing for the detection of SARS-CoV-2 infection with rapid antigen tests. medRxiv Template for Manufacturers of Molecular and Antigen Diagnostic COVID-19 Tests for Non-Laboratory Use The authors would like to thank the technical staff of the Department of Infectious diseases for their excellent assistance. Furthermore, the authors thank Thibaut de Sablet of Clinact, France for providing medical writing support/editorial support in accordance with Good Publication Practice (GPP3) guidelines. The authors declare that there are no conflicts of interest. The data that support the findings of this study are available from the corresponding author upon reasonable request. http://orcid.org/0000-0002-2212-6873