{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2025,11,13]],"date-time":"2025-11-13T07:19:38Z","timestamp":1763018378488,"version":"build-2065373602"},"reference-count":34,"publisher":"MDPI AG","issue":"5","license":[{"start":{"date-parts":[[2021,5,1]],"date-time":"2021-05-01T00:00:00Z","timestamp":1619827200000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Viruses"],"abstract":"<jats:p>To complement RT-qPCR testing for diagnosis of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infections, many countries have introduced the use of rapid antigen tests. As they generally display lower real-life performances than expected, their correct positioning as frontline screening is still controversial. Despite the lack of data from daily clinical use, third generation microfluidic assays (such as the LumiraDx SARS-CoV-2 Ag test) have recently been suggested to have similar performances to RT-qPCR and have been proposed as alternative diagnostic tools. By analyzing 960 nasopharyngeal swabs from 960 subjects at the emergency department admissions of a tertiary COVID-19 hospital, LumiraDx assay demonstrated a specificity of 97% (95% CI: 96\u201398), and a sensitivity of 85% (95% CI: 82\u201389) in comparison with RT-qPCR, which increases to 91% (95% CI: 86\u201395) for samples with a cycle threshold \u2264 29. Fifty false-negative LumiraDx-results were confirmed by direct quantification of genomic SARS-CoV-2 RNA through droplet-digital PCR (median (IQR) load = 5880 (1657\u201341,440) copies\/mL). Subgenomic N and E RNAs were detected in 52% (n = 26) and 56% (n = 28) of them, respectively, supporting the presence of active viral replication. Overall, the LumiraDx test complies with the minimum performance requirements of the WHO. Yet, the risk of a misrecognition of patients with active COVID-19 persists, and the need for confirmatory RT-qPCR should not be amended.<\/jats:p>","DOI":"10.3390\/v13050818","type":"journal-article","created":{"date-parts":[[2021,5,1]],"date-time":"2021-05-01T21:35:39Z","timestamp":1619904939000},"page":"818","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":17,"title":["Frontline Screening for SARS-CoV-2 Infection at Emergency Department Admission by Third Generation Rapid Antigen Test: Can We Spare RT-qPCR?"],"prefix":"10.3390","volume":"13","author":[{"given":"Valeria","family":"Cento","sequence":"first","affiliation":[{"name":"Department of Oncology and Hemato-Oncology, Universit\u00e0 degli Studi di Milano, 20122 Milan, Italy"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Silvia","family":"Renica","sequence":"additional","affiliation":[{"name":"Department of Oncology and Hemato-Oncology, Universit\u00e0 degli Studi di Milano, 20122 Milan, Italy"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Elisa","family":"Matarazzo","sequence":"additional","affiliation":[{"name":"Residency in Microbiology and Virology, Universit\u00e0 degli Studi di Milano, 20122 Milan, Italy"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Maria","family":"Antonello","sequence":"additional","affiliation":[{"name":"Department of Oncology and Hemato-Oncology, Universit\u00e0 degli Studi di Milano, 20122 Milan, Italy"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Luna","family":"Colagrossi","sequence":"additional","affiliation":[{"name":"Unit of Microbiology and Diagnostic Immunology, IRCCS Bambino Ges\u00f9 Children\u2019s Hospital, 00165 Rome, Italy"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Federica","family":"Di Ruscio","sequence":"additional","affiliation":[{"name":"Residency in Microbiology and Virology, Universit\u00e0 degli Studi di Milano, 20122 Milan, Italy"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-6464-2596","authenticated-orcid":false,"given":"Arianna","family":"Pani","sequence":"additional","affiliation":[{"name":"Department of Oncology and Hemato-Oncology, Universit\u00e0 degli Studi di Milano, 20122 Milan, Italy"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Diana","family":"Fanti","sequence":"additional","affiliation":[{"name":"Department of Chemical-Clinical and Microbiological Analyses, ASST Grande Ospedale Metropolitano Niguarda, 20162 Milan, Italy"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Chiara","family":"Vismara","sequence":"additional","affiliation":[{"name":"Department of Chemical-Clinical and Microbiological Analyses, ASST Grande Ospedale Metropolitano Niguarda, 20162 Milan, Italy"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Massimo","family":"Puoti","sequence":"additional","affiliation":[{"name":"Infectious Diseases Unit, ASST Grande Ospedale Metropolitano Niguarda, 20162 Milan, Italy"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-8554-2401","authenticated-orcid":false,"given":"Francesco","family":"Scaglione","sequence":"additional","affiliation":[{"name":"Department of Oncology and Hemato-Oncology, Universit\u00e0 degli Studi di Milano, 20122 Milan, Italy"},{"name":"Department of Chemical-Clinical and Microbiological Analyses, ASST Grande Ospedale Metropolitano Niguarda, 20162 Milan, Italy"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Carlo","family":"Perno","sequence":"additional","affiliation":[{"name":"Unit of Microbiology and Diagnostic Immunology, IRCCS Bambino Ges\u00f9 Children\u2019s Hospital, 00165 Rome, Italy"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-4270-5079","authenticated-orcid":false,"given":"Claudia","family":"Alteri","sequence":"additional","affiliation":[{"name":"Department of Oncology and Hemato-Oncology, Universit\u00e0 degli Studi di Milano, 20122 Milan, Italy"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"name":"on behalf of the S.Co.Va Study Group","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"1968","published-online":{"date-parts":[[2021,5,1]]},"reference":[{"unstructured":"Bundesministerium f\u00fcr Soziales Gesundheit Pflege und Konsumentenschutz (BMSGMPK) (2020). \u00d6sterreichische Teststrategie SARS-CoV-2, Bundesministerium f\u00fcr Soziales, Gesundheit, Pflege und Konsumentenschutz. Available online: https:\/\/www.sozialministerium.at\/Informationen-zum-Coronavirus\/Neuartiges-Coronavirus-(2019-nCov).html.","key":"ref_1"},{"unstructured":"Haute Autorit\u00e9 de Sant\u00e9 (HAS) (2021, February 02). Revue Rapide sur les Tests de D\u00e9tection Antig\u00e9nique du Virus SARS-CoV-2: HAS. Available online: https:\/\/www.has-sante.fr\/jcms\/p_3213483\/fr\/revue-rapide-sur-les-tests-de-detection-antigenique-du-virus-sars-cov-2.","key":"ref_2"},{"unstructured":"Ministero della Salute (MS) (2021, February 02). Aggiornamento della Definizione di Caso COVID-19 e Strategie di Testing, Available online: https:\/\/www.trovanorme.salute.gov.it\/norme\/renderNormsanPdf?anno=2021&codLeg=78155&parte=1%20&serie=null.","key":"ref_3"},{"unstructured":"Rijskinstituut voor Volksgmezondheid en Milieu (RIVM) (2021, February 02). Advies Antigeen(snel)testen: Government of the Netherlands. Available online: https:\/\/www.rijksoverheid.nl\/onderwerpen\/coronavirus-covid-19\/documenten\/rapporten\/2020\/10\/14\/advies-antigeensneltesten.","key":"ref_4"},{"unstructured":"Robert Koch Institut (RKI) (2020). Nationale Teststrategie SARS-CoV-2, RKI. Available online: https:\/\/www.rki.de\/DE\/Content\/InfAZ\/N\/Neuartiges_Coronavirus\/Teststrategie\/Nat-Teststrat.html.","key":"ref_5"},{"unstructured":"Servicio Nacional de Saude (SNS) (2021, February 02). Estrat\u00e9gia Nacional de Testes para SARS-CoV-2, Available online: http:\/\/www.insa.min-saude.pt\/covid-19-estrategia-nacional-de-testes-para-sars-cov-2.","key":"ref_6"},{"key":"ref_7","first-page":"eabf9648","article-title":"The impact of population-wide rapid antigen testing on SARS-CoV-2 prevalence in Slovakia","volume":"23","author":"Pavelka","year":"2021","journal-title":"Science"},{"unstructured":"European Center for Disease Prevention and Control (ECDC) (2021, February 02). Options for the Use of Rapid Antigen Tests for COVID-19 in the EU\/EEA and the UK. Available online: https:\/\/www.ecdc.europa.eu\/sites\/default\/files\/documents\/Options-use-of-rapid-antigen-tests-for-COVID-19.pdf.","key":"ref_8"},{"doi-asserted-by":"crossref","unstructured":"Str\u00f6mer, A., Rose, R., Sch\u00e4fer, M., Sch\u00f6n, F., Vollersen, A., Lorentz, T., Fickenscher, H., and Krumbholz, A. (2020). Performance of a Point-of-Care Test for the Rapid Detection of SARS-CoV-2 Antigen. Microorganisms, 9.","key":"ref_9","DOI":"10.3390\/microorganisms9010058"},{"key":"ref_10","doi-asserted-by":"crossref","first-page":"e00977-20","DOI":"10.1128\/JCM.00977-20","article-title":"Evaluation of a Rapid Diagnostic Assay for Detection of SARS-CoV-2 Antigen in Nasopharyngeal Swabs","volume":"58","author":"Cuffel","year":"2020","journal-title":"J. Clin. Microbiol."},{"key":"ref_11","doi-asserted-by":"crossref","first-page":"104455","DOI":"10.1016\/j.jcv.2020.104455","article-title":"Low performance of rapid antigen detection test as frontline testing for COVID-19 diagnosis","volume":"129","author":"Scohy","year":"2020","journal-title":"J. Clin. Virol."},{"key":"ref_12","doi-asserted-by":"crossref","first-page":"104659","DOI":"10.1016\/j.jcv.2020.104659","article-title":"Panbio antigen rapid test is reliable to diagnose SARS-CoV-2 infection in the first 7 days after the onset of symptoms","volume":"133","author":"Linares","year":"2020","journal-title":"J. Clin. Virol."},{"doi-asserted-by":"crossref","unstructured":"Drain, P.K., Ampajwala, M., Chappel, C., Gvozden, A.B., Hoppers, M., Wang, M., Rosen, R., Young, S., Zissman, E., and Montano, M. (2021). A rapid, high-sensitivity SARS-CoV-2 nucleocapsid immunoassay to aid diagnosis of acute COVID-19 at the point of care. Infect. Dis. Ther.","key":"ref_13","DOI":"10.1101\/2020.12.11.20238410"},{"doi-asserted-by":"crossref","unstructured":"Kohmer, N., Toptan, T., Pallas, C., Karaca, O., Pfeiffer, A., Westhaus, S., Widera, M., Berger, A., Hoehl, S., and Kammel, M. (2021). The Comparative Clinical Performance of Four SARS-CoV-2 Rapid Antigen Tests and Their Correlation to Infectivity In Vitro. J. Clin. Med., 10.","key":"ref_14","DOI":"10.3390\/jcm10020328"},{"unstructured":"World Health Organization (WHO) (2021, February 02). Coronavirus disease (COVID-19) Pandemic\u2014Emergency Use Listing Procedure (EUL) Open for In Vitro Diagnostics. Available online: https:\/\/www.who.int\/diagnostics_laboratory\/EUL\/en.","key":"ref_15"},{"unstructured":"US Centers for Disease Control and Prevention (CDC) (2021, February 02). Interim Guidance for Rapid Antigen Testing for SARS-CoV-2, Available online: https:\/\/www.cdc.gov\/coronavirus\/2019-ncov\/lab\/resources\/antigen-tests-guidelines.html.","key":"ref_16"},{"key":"ref_17","doi-asserted-by":"crossref","first-page":"465","DOI":"10.1038\/s41586-020-2196-x","article-title":"Virological assessment of hospitalized patients with COVID-2019","volume":"581","author":"Wolfel","year":"2020","journal-title":"Nature"},{"unstructured":"WHO (2021, January 12). Clinical Management of COVID-19. Available online: https:\/\/www.who.int\/publications\/i\/item\/clinical-management-of-covid-19.","key":"ref_18"},{"doi-asserted-by":"crossref","unstructured":"Alteri, C., Cento, V., Antonello, M., Colagrossi, L., Merli, M., Ughi, N., Renica, S., Matarazzo, E., Di Ruscio, F., and Tartaglione, L. (2020). Detection and quantification of SARS-CoV-2 by droplet digital PCR in real-time PCR negative nasopharyngeal swabs from suspected COVID-19 patients. PLoS ONE, 15.","key":"ref_19","DOI":"10.1371\/journal.pone.0236311"},{"doi-asserted-by":"crossref","unstructured":"Liotti, F.M., Menchinelli, G., Marchetti, S., Posteraro, B., Landi, F., Sanguinetti, M., and Cattani, P. (2020). Assessment of SARS-CoV-2 RNA Test Results Among Patients Who Recovered From COVID-19 With Prior Negative Results. J. Am. Med. Assoc.","key":"ref_20","DOI":"10.1001\/jamainternmed.2020.7570"},{"key":"ref_21","doi-asserted-by":"crossref","first-page":"138","DOI":"10.1038\/s41420-020-00375-y","article-title":"Long-term SARS-CoV-2 RNA shedding and its temporal association to IgG seropositivity","volume":"6","author":"Agarwal","year":"2020","journal-title":"Cell Death Discov."},{"unstructured":"FIND (2021, February 03). SARS-CoV-2 Diagnostic Pipeline. Available online: https:\/\/www.finddx.org\/covid-19\/pipeline\/?avance=Commercialized&type=Rapid+diagnostic+tests&test_target=Antigen&status=all&section=immunoassays&action=default#diag_tab.","key":"ref_22"},{"key":"ref_23","doi-asserted-by":"crossref","first-page":"104684","DOI":"10.1016\/j.jcv.2020.104684","article-title":"Analytical sensitivity and clinical sensitivity of the three rapid antigen detection kits for detection of SARS-CoV-2 virus","volume":"133","author":"Mak","year":"2020","journal-title":"J. Clin. Virol."},{"key":"ref_24","doi-asserted-by":"crossref","first-page":"104654","DOI":"10.1016\/j.jcv.2020.104654","article-title":"Urgent need of rapid tests for SARS CoV-2 antigen detection: Evaluation of the SD-Biosensor antigen test for SARS-CoV-2","volume":"132","author":"Cerutti","year":"2020","journal-title":"J. Clin. Virol."},{"key":"ref_25","doi-asserted-by":"crossref","first-page":"328","DOI":"10.1016\/j.ijid.2020.05.098","article-title":"Evaluation of a novel antigen-based rapid detection test for the diagnosis of SARS-CoV-2 in respiratory samples","volume":"99","author":"Porte","year":"2020","journal-title":"Int. J. Infect. Dis."},{"key":"ref_26","doi-asserted-by":"crossref","first-page":"104713","DOI":"10.1016\/j.jcv.2020.104713","article-title":"Evaluation of a SARS-CoV-2 rapid antigen test: Potential to help reduce community spread?","volume":"135","author":"Toptan","year":"2020","journal-title":"J. Clin. Virol."},{"unstructured":"ABL (2021, February 05). LumiraDx SARS-CoV-2 Ag Test Specifications. Available online: https:\/\/www.lumiradx.com\/uk-en\/what-we-do\/diagnostics\/test-technology\/antigen-test.","key":"ref_27"},{"key":"ref_28","doi-asserted-by":"crossref","first-page":"2701","DOI":"10.3201\/eid2611.203219","article-title":"SARS-CoV-2 Virus Culture and Subgenomic RNA for Respiratory Specimens from Patients with Mild Coronavirus Disease","volume":"26","author":"Perera","year":"2020","journal-title":"Emerg. Infect. Dis."},{"unstructured":"Ford, L., Lee, C., Pray, I.W., Cole, D., Bigouette, J.P., Abedi, G.R., Bushman, D., Delahoy, M.J., Currie, D.W., and Cherney, B. (2021). Epidemiologic characteristics associated with SARS-CoV-2 antigen-based test results, rRT-PCR cycle threshold values, subgenomic RNA, and viral culture results from university testing. Clin. Infect. Dis.","key":"ref_29"},{"key":"ref_30","doi-asserted-by":"crossref","first-page":"1059","DOI":"10.1007\/s10096-020-03913-9","article-title":"Viral RNA load as determined by cell culture as a management tool for discharge of SARS-CoV-2 patients from infectious disease wards","volume":"39","author":"Andreani","year":"2020","journal-title":"Eur. J. Clin. Microbiol. Infect. Dis."},{"key":"ref_31","doi-asserted-by":"crossref","first-page":"1544","DOI":"10.1056\/NEJMoa2024671","article-title":"Evaluation of the mRNA-1273 Vaccine against SARS-CoV-2 in Nonhuman Primates","volume":"383","author":"Corbett","year":"2020","journal-title":"N. Engl. J. Med."},{"key":"ref_32","doi-asserted-by":"crossref","first-page":"578","DOI":"10.1038\/s41586-020-2608-y","article-title":"ChAdOx1 nCoV-19 vaccine prevents SARS-CoV-2 pneumonia in rhesus macaques","volume":"586","author":"Lambe","year":"2020","journal-title":"Nature"},{"key":"ref_33","doi-asserted-by":"crossref","first-page":"806","DOI":"10.1126\/science.abc6284","article-title":"DNA vaccine protection against SARS-CoV-2 in rhesus macaques","volume":"369","author":"Yu","year":"2020","journal-title":"Science"},{"key":"ref_34","doi-asserted-by":"crossref","first-page":"265","DOI":"10.1146\/annurev-virology-100114-055218","article-title":"Continuous and Discontinuous RNA Synthesis in Coronaviruses","volume":"2","author":"Sola","year":"2020","journal-title":"Annu. Rev. Virol."}],"container-title":["Viruses"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.mdpi.com\/1999-4915\/13\/5\/818\/pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,10,11]],"date-time":"2025-10-11T05:56:35Z","timestamp":1760162195000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.mdpi.com\/1999-4915\/13\/5\/818"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2021,5,1]]},"references-count":34,"journal-issue":{"issue":"5","published-online":{"date-parts":[[2021,5]]}},"alternative-id":["v13050818"],"URL":"https:\/\/doi.org\/10.3390\/v13050818","relation":{},"ISSN":["1999-4915"],"issn-type":[{"type":"electronic","value":"1999-4915"}],"subject":[],"published":{"date-parts":[[2021,5,1]]}}}