{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,29]],"date-time":"2026-09-29T05:51:53Z","timestamp":1790661113455,"version":"4.1.0"},"reference-count":22,"publisher":"Oxford University Press (OUP)","issue":"5","license":[{"start":{"date-parts":[[2021,1,2]],"date-time":"2021-01-02T00:00:00Z","timestamp":1609545600000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/academic.oup.com\/journals\/pages\/open_access\/funder_policies\/chorus\/standard_publication_model"}],"funder":[{"name":"French Defence Innovation Agency\u2014Agence de l\u2019Innovation de D\u00e9fense","award":["N\u00b02020 68 0918 00 00 00 00"],"award-info":[{"award-number":["N\u00b02020 68 0918 00 00 00 00"]}]},{"name":"Rouen University Hospital"},{"name":"Ministre des arm\u00e9es"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"published-print":{"date-parts":[[2021,4,29]]},"abstract":"<jats:title>Abstract<\/jats:title>\n                  <jats:sec>\n                    <jats:title>Background<\/jats:title>\n                    <jats:p>Reverse transcription-quantitative PCR on nasopharyngeal swabs is currently the reference COVID-19 diagnosis method but exhibits imperfect sensitivity.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Methods<\/jats:title>\n                    <jats:p>We developed a multiplex reverse transcription-digital droplet PCR (RT-ddPCR) assay, targeting 6 SARS-CoV-2 genomic regions, and evaluated it on nasopharyngeal swabs and saliva samples collected from 130 COVID-19 positive or negative ambulatory individuals, who presented symptoms suggestive of mild or moderate SARS-CoV2 infection.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results<\/jats:title>\n                    <jats:p>For the nasopharyngeal swab samples, the results obtained using the 6-plex RT-ddPCR and RT-qPCR assays were all concordant. The 6-plex RT-ddPCR assay was more sensitive than RT-qPCR (85% versus 62%) on saliva samples from patients with positive nasopharyngeal swabs.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusion<\/jats:title>\n                    <jats:p>Multiplex RT-ddPCR represents an alternative and complementary tool for the diagnosis of COVID-19, in particular to control RT-qPCR ambiguous results. It can also be applied to saliva for repetitive sampling and testing individuals for whom nasopharyngeal swabbing is not possible.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.1093\/clinchem\/hvaa323","type":"journal-article","created":{"date-parts":[[2020,12,16]],"date-time":"2020-12-16T09:09:23Z","timestamp":1608109763000},"page":"736-741","source":"Crossref","is-referenced-by-count":35,"title":["Assessment of Multiplex Digital Droplet RT-PCR as a Diagnostic Tool for SARS-CoV-2 Detection in Nasopharyngeal Swabs and Saliva Samples"],"prefix":"10.1093","volume":"67","author":[{"given":"K\u00e9vin","family":"Cassinari","sequence":"first","affiliation":[{"name":"Department of Genetics, Rouen University Hospital and Inserm U1245, UNIROUEN, Normandie University, Normandy Center for Genomic and Personalized Medicine, Rouen, France"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Elodie","family":"Alessandri-Gradt","sequence":"additional","affiliation":[{"name":"Virology Laboratory, Rouen University Hospital, Rouen, France"},{"name":"Research Group on Microbial Adaptation, GRAM, UNIROUEN, Normandie University, Rouen, France"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Pascal","family":"Chambon","sequence":"additional","affiliation":[{"name":"Department of Genetics, Rouen University Hospital and Inserm U1245, UNIROUEN, Normandie University, Normandy Center for Genomic and Personalized Medicine, Rouen, France"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Fran\u00e7oise","family":"Charbonnier","sequence":"additional","affiliation":[{"name":"Department of Genetics, Rouen University Hospital and Inserm U1245, UNIROUEN, Normandie University, Normandy Center for Genomic and Personalized Medicine, Rouen, France"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"S\u00e9gol\u00e8ne","family":"Gracias","sequence":"additional","affiliation":[{"name":"Virology Laboratory, Rouen University Hospital, Rouen, France"},{"name":"Research Group on Microbial Adaptation, GRAM, UNIROUEN, Normandie University, Rouen, France"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ludivine","family":"Beaussire","sequence":"additional","affiliation":[{"name":"Department of Genetics, Rouen University Hospital and Inserm U1245, UNIROUEN, Normandie University, Normandy Center for Genomic and Personalized Medicine, Rouen, France"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Kevin","family":"Alexandre","sequence":"additional","affiliation":[{"name":"Research Group on Microbial Adaptation, GRAM, UNIROUEN, Normandie University, Rouen, France"},{"name":"Department of Infectious Diseases, Rouen University Hospital, Rouen, France"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Nasrin","family":"Sarafan-Vasseur","sequence":"additional","affiliation":[{"name":"Department of Genetics, Rouen University Hospital and Inserm U1245, UNIROUEN, Normandie University, Normandy Center for Genomic and Personalized Medicine, Rouen, France"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Claude","family":"Houdayer","sequence":"additional","affiliation":[{"name":"Department of Genetics, Rouen University Hospital and Inserm U1245, UNIROUEN, Normandie University, Normandy Center for Genomic and Personalized Medicine, Rouen, France"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Manuel","family":"Etienne","sequence":"additional","affiliation":[{"name":"Research Group on Microbial Adaptation, GRAM, UNIROUEN, Normandie University, Rouen, France"},{"name":"Department of Infectious Diseases, Rouen University Hospital, Rouen, France"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Fran\u00e7ois","family":"Caron","sequence":"additional","affiliation":[{"name":"Research Group on Microbial Adaptation, GRAM, UNIROUEN, Normandie University, Rouen, France"},{"name":"Department of Infectious Diseases, Rouen University Hospital, Rouen, France"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jean Christophe","family":"Plantier","sequence":"additional","affiliation":[{"name":"Virology Laboratory, Rouen University Hospital, Rouen, France"},{"name":"Research Group on Microbial Adaptation, GRAM, UNIROUEN, Normandie University, Rouen, France"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Thierry","family":"Frebourg","sequence":"additional","affiliation":[{"name":"Department of Genetics, Rouen University Hospital and Inserm U1245, UNIROUEN, Normandie University, Normandy Center for Genomic and Personalized Medicine, Rouen, France"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"286","published-online":{"date-parts":[[2021,1,2]]},"reference":[{"key":"2021043007563247700_hvaa323-B1","doi-asserted-by":"crossref","first-page":"672","DOI":"10.1038\/s41591-020-0869-5","article-title":"Temporal dynamics in viral shedding and transmissibility of COVID-19","volume":"26","author":"He","year":"2020","journal-title":"Nat Med"},{"key":"2021043007563247700_hvaa323-B2","doi-asserted-by":"crossref","first-page":"899","DOI":"10.1093\/infdis\/jiaa370","article-title":"Suboptimal biological sampling as a probable cause of false-negative COVID-19 diagnostic test results","volume":"222","author":"Kinloch","year":"2020","journal-title":"J Infect Dis"},{"key":"2021043007563247700_hvaa323-B3","doi-asserted-by":"crossref","first-page":"104821","DOI":"10.1016\/j.oraloncology.2020.104821","article-title":"Oral saliva and COVID-19","volume":"108","author":"Baghizadeh Fini","year":"2020","journal-title":"Oral Oncol"},{"key":"2021043007563247700_hvaa323-B4","doi-asserted-by":"crossref","DOI":"10.1002\/rmv.2185","article-title":"Alternative clinical specimens for the detection of SARS-CoV-2: A rapid review","author":"Comber","year":"2020","journal-title":"Rev Med Virol"},{"key":"2021043007563247700_hvaa323-B5","article-title":"The positive rate of saliva for the detection of nCoV and possible factors related to the sensitivity results","volume":"2020","author":"Meng","journal-title":"J Med Virol"},{"key":"2021043007563247700_hvaa323-B6","doi-asserted-by":"crossref","DOI":"10.3346\/jkms.2020.35.e195","article-title":"Clinical significance of a high SARS-CoV-2 viral load in the saliva","volume":"35","author":"Yoon","year":"2020","journal-title":"J Korean Med Sci"},{"key":"2021043007563247700_hvaa323-B7","first-page":"7","article-title":"Digital droplet PCR: CNV analysis and other applications","volume":"82","author":"Mazaika","year":"2014","journal-title":"Curr Protoc Hum Genet"},{"key":"2021043007563247700_hvaa323-B8","doi-asserted-by":"crossref","first-page":"9236","DOI":"10.1073\/pnas.96.16.9236","article-title":"Digital PCR","volume":"96","author":"Vogelstein","year":"1999","journal-title":"Proc Natl Acad Sci USA"},{"key":"2021043007563247700_hvaa323-B9","doi-asserted-by":"crossref","first-page":"79","DOI":"10.1373\/clinchem.2014.221366","article-title":"Considerations for digital PCR as an accurate molecular diagnostic tool","volume":"61","author":"Huggett","year":"2015","journal-title":"Clin Chem"},{"key":"2021043007563247700_hvaa323-B10","doi-asserted-by":"crossref","first-page":"1360","DOI":"10.1111\/tbed.13168","article-title":"Reverse transcriptase droplet digital PCR to identify the emerging vesicular virus Senecavirus A in biological samples","volume":"66","author":"Pinheiro-de-Oliveira","year":"2019","journal-title":"Transbound Emerg Dis"},{"key":"2021043007563247700_hvaa323-B11","doi-asserted-by":"crossref","first-page":"1175","DOI":"10.1080\/22221751.2020.1772679","article-title":"Analytical comparisons of SARS-COV-2 detection by qRT-PCR and ddPCR with multiple primer\/probe sets","volume":"9","author":"Liu","year":"2020","journal-title":"Emerg Microbes Infect"},{"key":"2021043007563247700_hvaa323-B12","doi-asserted-by":"crossref","first-page":"1259","DOI":"10.1080\/22221751.2020.1772678","article-title":"ddPCR: a more accurate tool for SARS-CoV-2 detection in low viral load specimens","volume":"9","author":"Suo","year":"2020","journal-title":"Emerg Microbes Infect"},{"key":"2021043007563247700_hvaa323-B13","doi-asserted-by":"crossref","first-page":"793","DOI":"10.1093\/cid\/ciaa345","article-title":"Quantitative detection and viral load analysis of SARS-CoV-2 in infected patients","volume":"71","author":"Yu","year":"2020","journal-title":"Clin Infect Dis"},{"key":"2021043007563247700_hvaa323-B14","doi-asserted-by":"crossref","first-page":"720","DOI":"10.1111\/irv.12769","article-title":"A six-plex droplet digital RT-PCR assay for seasonal influenza virus typing, subtyping, and lineage determination","volume":"14","author":"Leong","year":"2020","journal-title":"Influenza Other Respi Viruses"},{"key":"2021043007563247700_hvaa323-B15","doi-asserted-by":"crossref","first-page":"996","DOI":"10.1101\/gr.229102","article-title":"The Human Genome Browser at UCSC","volume":"12","author":"Kent","year":"2002","journal-title":"Genome Res"},{"key":"2021043007563247700_hvaa323-B16","doi-asserted-by":"crossref","first-page":"W29","DOI":"10.1093\/nar\/gkt282","article-title":"BLAST: a more efficient report with usability improvements","volume":"41","author":"Boratyn","year":"2013","journal-title":"Nucleic Acids Res"},{"key":"2021043007563247700_hvaa323-B17","doi-asserted-by":"crossref","first-page":"1003","DOI":"10.1038\/nmeth.2633","article-title":"Absolute quantification by droplet digital PCR versus analog real-time PCR","volume":"10","author":"Hindson","year":"2013","journal-title":"Nat Methods"},{"key":"2021043007563247700_hvaa323-B18","doi-asserted-by":"crossref","first-page":"12620","DOI":"10.1038\/s41598-019-49043-x","article-title":"Optimisation of robust singleplex and multiplex droplet digital PCR assays for high confidence mutation detection in circulating tumour DNA","volume":"9","author":"Rowlands","year":"2019","journal-title":"Sci Rep"},{"key":"2021043007563247700_hvaa323-B19","doi-asserted-by":"crossref","first-page":"1012","DOI":"10.1093\/clinchem\/hvaa125","article-title":"The digital MIQE guidelines update: minimum information for publication of quantitative digital PCR experiments for 2020","volume":"66","author":"Whale","year":"2020","journal-title":"Clin Chem"},{"key":"2021043007563247700_hvaa323-B20","doi-asserted-by":"crossref","first-page":"1670","DOI":"10.1373\/clinchem.2013.211045","article-title":"Tolerance of droplet-digital PCR versus real-time quantitative PCR to inhibitory substances","volume":"59","author":"Dingle","year":"2013","journal-title":"Clin Chem"},{"key":"2021043007563247700_hvaa323-B21","doi-asserted-by":"crossref","first-page":"e0229791","DOI":"10.1371\/journal.pone.0229791","article-title":"An optimised saliva collection method to produce high-yield, high-quality RNA for translational research","volume":"15","author":"Sullivan","year":"2020","journal-title":"PLoS One"},{"key":"2021043007563247700_hvaa323-B22","doi-asserted-by":"crossref","DOI":"10.1093\/cid\/ciaa1388","article-title":"Mass screening of asymptomatic persons for SARS-CoV-2 using saliva","author":"Yokota","year":"2020","journal-title":"Clin Infect Dis"}],"container-title":["Clinical Chemistry"],"original-title":[],"language":"en","link":[{"URL":"http:\/\/academic.oup.com\/clinchem\/advance-article-pdf\/doi\/10.1093\/clinchem\/hvaa323\/35350018\/hvaa323.pdf","content-type":"application\/pdf","content-version":"am","intended-application":"syndication"},{"URL":"http:\/\/academic.oup.com\/clinchem\/article-pdf\/67\/5\/736\/37582489\/hvaa323.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"syndication"},{"URL":"http:\/\/academic.oup.com\/clinchem\/article-pdf\/67\/5\/736\/37582489\/hvaa323.pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2021,4,30]],"date-time":"2021-04-30T03:58:29Z","timestamp":1619755109000},"score":1,"resource":{"primary":{"URL":"https:\/\/academic.oup.com\/clinchem\/article\/67\/5\/736\/6040733"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2021,1,2]]},"references-count":22,"journal-issue":{"issue":"5","published-online":{"date-parts":[[2021,1,2]]},"published-print":{"date-parts":[[2021,4,29]]}},"URL":"https:\/\/doi.org\/10.1093\/clinchem\/hvaa323","relation":{"has-preprint":[{"id-type":"doi","id":"10.1101\/2020.08.02.20166694","asserted-by":"object"}]},"ISSN":["0009-9147","1530-8561"],"issn-type":[{"value":"0009-9147","type":"print"},{"value":"1530-8561","type":"electronic"}],"subject":[],"published-other":{"date-parts":[[2021,5,1]]},"published":{"date-parts":[[2021,1,2]]}}}