{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,6,30]],"date-time":"2026-06-30T00:22:15Z","timestamp":1782778935231,"version":"3.54.5"},"reference-count":19,"publisher":"Walter de Gruyter GmbH","issue":"5","funder":[{"DOI":"10.13039\/501100003985","name":"Fundaci\u00f3n Jos\u00e9 Luis Casta\u00f1o","doi-asserted-by":"publisher","id":[{"id":"10.13039\/501100003985","id-type":"DOI","asserted-by":"publisher"}]},{"name":"IFCC\u2019s Professional Scientific Exchange Programme"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"published-print":{"date-parts":[[2022,4,26]]},"abstract":"<jats:title>Abstract<\/jats:title>\n                  <jats:sec id=\"j_cclm-2021-1142_abs_001\">\n                    <jats:title>Objectives<\/jats:title>\n                    <jats:p>Widespread SARS-CoV-2 testing is invaluable for identifying asymptomatic\/pre-symptomatic individuals. There remains a technological gap for highly reliable, easy, and quick SARS-CoV-2 diagnostic tests suitable for frequent mass testing. Compared to nasopharyngeal (NP) swab-based tests, saliva-based methods are attractive due to easier and safer sampling. Current saliva-based SARS-CoV-2 rapid antigen tests (RATs) are hindered by limited analytical sensitivity. Here, we report one of the first ultrasensitive, saliva-based SARS-CoV-2 antigen assays with an analytical sensitivity of &lt;0.32\u00a0pg\/mL, corresponding to four viral RNA copies\/\u00b5L, which is comparable to that of PCR-based tests.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec id=\"j_cclm-2021-1142_abs_002\">\n                    <jats:title>Methods<\/jats:title>\n                    <jats:p>Using the novel electrochemiluminescence (ECL)-based immunoassay, we measured the SARS-CoV-2 nucleocapsid (N)\u00a0antigen concentration in 105 salivas, obtained from non-COVID-19 and COVID-19 patients. We then verified the results with a second, independent cohort of 689 patients (3.8% SARS-CoV-2 positivity rate). We also compared our method with a widely used point-of-care rapid test.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec id=\"j_cclm-2021-1142_abs_003\">\n                    <jats:title>Results<\/jats:title>\n                    <jats:p>In the first cohort, at 100% specificity, the sensitivity was 92%. Our assay correctly identified samples with viral loads up to 35 CT cycles by saliva-based PCR. Paired NP swab-based PCR results were obtained for 86 cases. Our assay showed high concordance with saliva-based and NP swab-based PCR in samples with negative (&lt;0.32\u00a0pg\/mL) and strongly positive (&gt;2\u00a0pg\/mL) N antigen concentrations. In the second cohort, at 100% specificity, sensitivity was also 92%. Our assay is about 700-fold more sensitive than the Abbott Panbio Rapid Test.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec id=\"j_cclm-2021-1142_abs_004\">\n                    <jats:title>Conclusions<\/jats:title>\n                    <jats:p>We demonstrated the ultrasensitivity and specificity assay and its concordance with PCR. This novel assay is especially valuable when compliance to frequent swabbing may be problematic.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.1515\/cclm-2021-1142","type":"journal-article","created":{"date-parts":[[2022,2,16]],"date-time":"2022-02-16T11:09:25Z","timestamp":1645009765000},"page":"771-777","source":"Crossref","is-referenced-by-count":14,"title":["Ultrasensitive assay for saliva-based SARS-CoV-2 antigen detection"],"prefix":"10.1515","volume":"60","author":[{"given":"Annie","family":"Ren","sequence":"first","affiliation":[{"name":"Department of Laboratory Medicine and Pathobiology , University of Toronto , Toronto , Canada"},{"name":"Lunenfeld-Tanenbaum Research Institute , Mount Sinai Hospital , Toronto , Canada"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Dorsa","family":"Sohaei","sequence":"additional","affiliation":[{"name":"Department of Laboratory Medicine and Pathobiology , University of Toronto , Toronto , Canada"},{"name":"Lunenfeld-Tanenbaum Research Institute , Mount Sinai Hospital , Toronto , Canada"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Antigona","family":"Ulndreaj","sequence":"additional","affiliation":[{"name":"Lunenfeld-Tanenbaum Research Institute , Mount Sinai Hospital , Toronto , Canada"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Oscar D.","family":"Pons-Belda","sequence":"additional","affiliation":[{"name":"Lunenfeld-Tanenbaum Research Institute , Mount Sinai Hospital , Toronto , Canada"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Amaia","family":"Fernandez-Uriarte","sequence":"additional","affiliation":[{"name":"Lunenfeld-Tanenbaum Research Institute , Mount Sinai Hospital , Toronto , Canada"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ioannis","family":"Zacharioudakis","sequence":"additional","affiliation":[{"name":"Biology Department , University of Crete , Heraklion , Crete , Greece"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"George B.","family":"Sigal","sequence":"additional","affiliation":[{"name":"Meso Scale Diagnostics, LLC. (MSD) , Rockville , MD , USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Martin","family":"Stengelin","sequence":"additional","affiliation":[{"name":"Meso Scale Diagnostics, LLC. (MSD) , Rockville , MD , USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Anu","family":"Mathew","sequence":"additional","affiliation":[{"name":"Meso Scale Diagnostics, LLC. (MSD) , Rockville , MD , USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Christopher","family":"Campbell","sequence":"additional","affiliation":[{"name":"Meso Scale Diagnostics, LLC. (MSD) , Rockville , MD , USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Nikhil","family":"Padmanabhan","sequence":"additional","affiliation":[{"name":"Meso Scale Diagnostics, LLC. (MSD) , Rockville , MD , USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Daniel","family":"Romero","sequence":"additional","affiliation":[{"name":"Meso Scale Diagnostics, LLC. (MSD) , Rockville , MD , USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jessica","family":"Joe","sequence":"additional","affiliation":[{"name":"Meso Scale Diagnostics, LLC. (MSD) , Rockville , MD , USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Antoninus","family":"Soosaipillai","sequence":"additional","affiliation":[{"name":"Department of Pathology and Laboratory Medicine , Mount Sinai Hospital , Toronto , Canada"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Vathany","family":"Kulasingam","sequence":"additional","affiliation":[{"name":"Department of Laboratory Medicine and Pathobiology , University of Toronto , Toronto , Canada"},{"name":"Department of Clinical Biochemistry , University Health Network , Toronto , ON , Canada"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Tony","family":"Mazzulli","sequence":"additional","affiliation":[{"name":"Department of Laboratory Medicine and Pathobiology , University of Toronto , Toronto , Canada"},{"name":"Department of Microbiology , University Health Network, Mount Sinai Hospital , Toronto , Canada"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Xinliu A.","family":"Li","sequence":"additional","affiliation":[{"name":"Department of Microbiology , University Health Network, Mount Sinai Hospital , Toronto , Canada"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Allison","family":"McGeer","sequence":"additional","affiliation":[{"name":"Department of Laboratory Medicine and Pathobiology , University of Toronto , Toronto , Canada"},{"name":"Department of Microbiology , University Health Network, Mount Sinai Hospital , Toronto , Canada"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-1589-820X","authenticated-orcid":false,"given":"Eleftherios P.","family":"Diamandis","sequence":"additional","affiliation":[{"name":"Department of Laboratory Medicine and Pathobiology , University of Toronto , Toronto , Canada"},{"name":"Lunenfeld-Tanenbaum Research Institute , Mount Sinai Hospital , Toronto , Canada"},{"name":"Department of Clinical Biochemistry , University Health Network , Toronto , ON , Canada"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ioannis","family":"Prassas","sequence":"additional","affiliation":[{"name":"Lunenfeld-Tanenbaum Research Institute , Mount Sinai Hospital , Toronto , Canada"},{"name":"Department of Pathology and Laboratory Medicine , Mount Sinai Hospital , Toronto , Canada"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"374","published-online":{"date-parts":[[2022,2,16]]},"reference":[{"key":"2023033111480992936_j_cclm-2021-1142_ref_001","doi-asserted-by":"crossref","unstructured":"Medicine, TLR. 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BMJ 2020;370:m3262. https:\/\/doi.org\/10.1136\/bmj.m3262.","DOI":"10.1136\/bmj.m3262"},{"key":"2023033111480992936_j_cclm-2021-1142_ref_004","doi-asserted-by":"crossref","unstructured":"Wyllie, AL, Fournier, J, Casanovas-Massana, A, Campbell, M, Tokuyama, M, Vijayakumar, P, et al.. Saliva or nasopharyngeal swab specimens for detection of SARS-CoV-2. N Engl J Med 2020;383:1283\u20136. https:\/\/doi.org\/10.1056\/nejmc2016359.","DOI":"10.1056\/NEJMc2016359"},{"key":"2023033111480992936_j_cclm-2021-1142_ref_005","doi-asserted-by":"crossref","unstructured":"Medeiros, RC, Nogueira, LC, de Ara\u00fajo, DN, Costa, K, Pirih, FQ, Luz de Aquino, AR. Saliva as a possible tool for the SARS-CoV-2 detection: a review. Trav Med Infect Dis 2020;38:101920. https:\/\/doi.org\/10.1016\/j.tmaid.2020.101920.","DOI":"10.1016\/j.tmaid.2020.101920"},{"key":"2023033111480992936_j_cclm-2021-1142_ref_006","doi-asserted-by":"crossref","unstructured":"Comber, L, Walsh, KA, Jordan, K, O\u2019Brien, KK, Clyne, B, Teljeur, C, et al.. Alternative clinical specimens for the detection of SARS\u2010CoV\u20102: a rapid review. Rev Med Virol 2021;31:e2185. https:\/\/doi.org\/10.1002\/rmv.2185.","DOI":"10.1002\/rmv.2185"},{"key":"2023033111480992936_j_cclm-2021-1142_ref_007","doi-asserted-by":"crossref","unstructured":"Michailidou, E, Poulopoulos, A, Tzimagiorgis, G. Salivary diagnostics of the novel coronavirus SARS\u2010CoV\u20102 (COVID\u201019). Oral Dis 2020. https:\/\/doi.org\/10.1111\/odi.13729 [Epub ahead of print].","DOI":"10.1111\/odi.13729"},{"key":"2023033111480992936_j_cclm-2021-1142_ref_008","doi-asserted-by":"crossref","unstructured":"Butler-Laporte, G, Lawandi, A, Schiller, I, Yao, MC, Dendukuri, N, McDonald, EG, et al.. Comparison of saliva and nasopharyngeal swab nucleic acid amplification testing for detection of SARS-CoV-2: a systematic review and meta-analysis. JAMA Intern Med 2021;181:353\u201360. https:\/\/doi.org\/10.1001\/jamainternmed.2020.8876.","DOI":"10.1001\/jamainternmed.2020.8876"},{"key":"2023033111480992936_j_cclm-2021-1142_ref_009","doi-asserted-by":"crossref","unstructured":"Ning, B, Yu, T, Zhang, S, Huang, Z, Tian, D, Lin, Z, et al.. A smartphone-read ultrasensitive and quantitative saliva test for COVID-19. 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Fast coronavirus tests: what they can and can\u2019t do. Nature 2020;585:496\u20138. https:\/\/doi.org\/10.1038\/d41586-020-02661-2.","DOI":"10.1038\/d41586-020-02661-2"},{"key":"2023033111480992936_j_cclm-2021-1142_ref_013","doi-asserted-by":"crossref","unstructured":"Jamal, AJ, Mozafarihashjin, M, Coomes, E, Powis, J, Li, AX, Paterson, A, et al.. Sensitivity of nasopharyngeal swabs and saliva for the detection of severe acute respiratory syndrome coronavirus 2. Clin Infect Dis 2021;72:1064\u20136. https:\/\/doi.org\/10.1093\/cid\/ciaa848.","DOI":"10.1093\/cid\/ciaa848"},{"key":"2023033111480992936_j_cclm-2021-1142_ref_014","doi-asserted-by":"crossref","unstructured":"Shan, D, Johnson, JM, Fernandes, SC, Suib, H, Hwang, S, Wuelfing, D, et al.. N-protein presents early in blood, dried blood and saliva during asymptomatic and symptomatic SARS-CoV-2 infection. 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