key: cord-0943844-19bjhb0r
authors: Stohr, J.J.J.M.; Zwart, V.F.; Goderski, G.; Meijer, A.; Nagel-Imming, C.R.S.; Kluytmans-van den Bergh, M.F.Q.; Pas, S.D.; van den Oetelaar, F.; Hellwich, M.; Gan, K.H.; Rietveld, A.; Verweij, J.J.; Murk, J.L.; van den Bijllaardt, W.; Kluytmans, J.A.J.W.
title: Self-testing for the detection of SARS-CoV-2 infection with rapid antigen tests for people with suspected COVID-19 in the community
date: 2021-08-04
journal: Clin Microbiol Infect
DOI: 10.1016/j.cmi.2021.07.039
sha: 8cd021f189de2fdcec5a0f5c644e82e90c1399ee
doc_id: 943844
cord_uid: 19bjhb0r

OBJECTIVES: Self-testing for COVID-19 infection with lateral flow assay SARS-CoV-2 rapid antigen detection tests (RDT), provides rapid results and could enable frequent and extensive testing in the community, thereby improving the control of SARS-CoV-2. The objective of this study was to evaluate the performance of nasal mid-turbinate self-testing using RDT for persons suspected with COVID-19 in the community. METHODS: Participants visiting a municipal SARS-CoV-2 testing centre, received self-testing kits containing either the BD Veritor System (BD-RDT) or Roche SARS-CoV-2 antigen detection test (Roche-RDT). Oro-nasopharyngeal swabs were collected from the participants for qRT-PCR testing. As a proxy for contagiousness, viral culture was performed on a selection of qRT-PCR positive samples to determine the Ct-value at which the chance of a positive culture was dropping below 0.5 (Ct-value cut-off). Sensitivity and specificity of self-testing were compared to qRT-PCR with a Ct-value below the Ct value cut-off. Determinants independently associated with a false-negative self-test result were determined. RESULTS: A total of 3,201 participants were included (BD-RDT n=1595; Roche-RDT n=1606). Sensitivity and specificity of self-testing compared to the qRT-PCR results with a Ct-value below the Ct-value cut-off was 78.4% (95% CI:73.2-83.5) and 99.4% (95%CI: 99.1-99.7) respectively. A higher age was independently associated with a false-negative self-testing result with an odds ratio of 1.024 (95%CI:1.003-1.044). CONCLUSIONS: Self-testing using currently available RDT’s has a high specificity and relatively high sensitivity to identify individuals with a high probability of contagiousness.

Extensive testing of individuals who are potentially infected with SARS-CoV-2, has a central role in efforts to 40 mitigate the spread of SARS-CoV-2 (1,2). Self-testing for SARS-CoV-2 infection could enable massive testing in 41 the community, thereby improving the control of SARS-CoV-2 (3,4). Lateral flow assay SARS-CoV-2 antigen tests 42 (RDT) , could be suitable candidates for self-testing for SARS-CoV-2 infection (5-7). Studies on the performance 43 of these RDT have shown promising results when samples were collected and performed by qualified personnel 44 (5-7). Recent reports have established the achievability of nasal mid-turbinate self-sampling under supervision 45 (8) (9) (10) . Data on the performance of self-testing with RDT is limited to comparisons with real-time reverse 46 transcription polymerase chain reaction (qRT-PCR) detection of SARS-CoV-2 RNA. qRT-PCR detects intact virus 47 but also non-transmittable SARS-CoV-2 RNA (11, 12) , and could overestimate the number of contagious 48 patients. Other reports have tried to overcome this limitation by stratifying the results for the cycle threshold 49 value (Ct-value) of the qRT-PCR (5,6). However, the Ct-value at which patients are expected to be no longer 50 contagious is unknown for most qRT-PCR assays and patient populations. The objective of this study is to 51 evaluate the performance of self-testing for persons with suspected COVID-19 (e.g., patients with COVID-19 52 related symptoms or close contacts of patients with COVID-19) using two commercially available RDT i.e., BD This manufacturer-independent cross-sectional study was conducted from December 23, 2020, to January, 17, 60 2021, in the test centre of the Municipal Health Services (MHS) in Tilburg, Noord-Brabant, the Netherlands. In 61 the Netherlands community testing for SARS-CoV-2 is coordinated by the MHS. Persons with COVID-19 related 62 symptoms or persons with close contact with a confirmed COVID-19 patient, can make a free of charge 63 appointment at these test centres for a SARS-CoV-2 test, without consulting a health-care professional.

Consecutive persons aged 18 years or older who presented at the test centre, were able to understand the Eligible participants were randomly allocated by a traffic controller to either a test lane distributing the BD-RDT 69 self-testing kit or a test lane distributing the Roche-RDT self-testing kit. Participants received a small bag with 70 the self-testing kit, were instructed to perform the SARS-CoV-2 self-test immediately after arrival at-home and 71 were asked to provide their e-mail address and telephone number. At the test centre, the by that time 72 prevailing method for SARS-CoV-2 testing was carried out. Both an oropharyngeal and a nasopharyngeal swab 73 was collected from the participants by a trained member of the MHS and both swabs were suspended in a 74 single container with 3 mL gelatin-lactalbumin-yeast virus transport (GLY) medium (Mediaproducts, Groningen, 75 the Netherlands). The suspended swabs were sent to Microvida Laboratory for Medical Microbiology and 76 Immunology, Tilburg, the Netherlands, for qRT-PCR testing within 4 hours after sample collection. Participants 77 received an e-mail with a link to a digital survey form. The survey content is presented in Supplementary 78 methods S1. Results of the RDT had to be available to the study team before qRT-PCR results were 79 communicated with the participant. When the participant did not complete the survey within two hours 80 following inclusion, the participant was telephoned by a member of the research team to fill in the survey form 81 jointly. If the participant did not yet perform the self-test when being telephoned, the member of the research 82 team asked the participant to perform the test and fill in the survey form sent via e-mail. Participants were not 83 assisted during the self-testing procedure.

Self-testing positive qRT-PCR result, that were collected before January 12, 2021, were sent for viral culture. An extensive 96 description of virus culture and qRT-PCR protocol is added as Supplementary method S4 (13-15).

Sample size 98 At the start of the study, the diagnostic accuracy of self-performed RDT was unknown. We assumed the 99 diagnostic accuracy to be lower than when performed by professionals, and based the sample size calculation 100 on an expected sensitivity of 80% for infectious individuals, with a margin of error of 7%, type I error of 5% and 101 power of 90%. Hence, the minimum number of participants with a positive qRT-PCR test was 140 per RDT arm.

The qRT-PCR test positivity percentage was monitored over time and recruitment was adjusted if needed. the Ct-value cut-off. The association between a false negative test result in the self-test as compared to the 159 qRT-PCR with a Ct-value below the Ct-value cut-off was investigated for 5 variables using a univariate logistic 160 regression model ( Table 3) . Out of these 5 variables, 2 variables were associated with the occurrence of a false 161 negative self-test result with a p-value < 0.2 and were included in the multivariate analysis ( lower. Using a model rather than culture positivity could eliminate possible circumstances that would have 217 resulted in false negative culture results in specific samples (e.g., long time before freezing a specific sample).

However, viral culture positivity is only a surrogate marker infectiousness. Therefore, infectious COVID-19 219 patients could have had a Ct-value in the SARS-CoV-2 qRT-PCR higher than the Ct-value cut-off.

In conclusion, we showed that self-testing using currently available RDT has a high specificity and relatively high 221 sensitivity (75%-80%) to identify individuals with a high probability of contagiousness. This application has the 222 potential for frequent and extensive testing which may be an aid to lift current restrictions to society. Positive qRT-PCR

Comparison of 276 molecular testing strategies for COVID-19 control: a mathematical modelling study

Assessment of SARS-CoV-2 Screening Strategies to Permit the Safe 280 Reopening of College Campuses in the United States

Regular universal 282 screening for SARS-CoV-2 infection may not allow reopening of society after controlling a pandemic 283 wave. medRxiv

Test sensitivity is secondary to 285 frequency and turnaround time for COVID-19 screening

Performance evaluation of a SARS-CoV-2 rapid antigentest: Test perfomance in the community in the 289 Netherlands

Real-life validation 291 of the Panbio TM COVID-19 antigen rapid test (Abbott) in community-dwelling subjects with symptoms 292 of potential SARS-CoV-2 infection. EClinicalMedicine

SARS-CoV-2 patient self-testing 301 with an antigen-detecting rapid test: a head-to-head comparison with professional testing

At-home self-testing of teachers with a 304

SARS-CoV-2 rapid antigen test to reduce potential transmissions in schools Results of the SAFE School 305

Duration 309 and key determinants of infectious virus shedding in hospitalized patients with coronavirus disease-310 2019 (COVID-19)

COVID-19 in 313 health-care workers in three hospitals in the south of the Netherlands: a cross-sectional study

Detection of 2019 novel 316 coronavirus (2019-nCoV) by real-time RT-PCR

Diagnosis of human metapneumovirus and 318 rhinovirus in patients with respiratory tract infections by an internally controlled multiplex real

Estimating 322 infectiousness throughout SARS-CoV-2 infection course

Effective screening 327 strategies for detection of asymptomatic COVID-19 travelers at airport quarantine stations: Exploratory 328 findings in Japan

We would like to thank all health-care, call-centre and supporting staff of the GGD test centre in Tilburg, the 226 Netherlands for their help in retrieving the samples and completion of the surveys. We would like to thank JvK