{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,4,13]],"date-time":"2026-04-13T09:23:05Z","timestamp":1776072185798,"version":"3.50.1"},"reference-count":41,"publisher":"Springer Science and Business Media LLC","issue":"1","license":[{"start":{"date-parts":[[2021,3,4]],"date-time":"2021-03-04T00:00:00Z","timestamp":1614816000000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0"},{"start":{"date-parts":[[2021,3,4]],"date-time":"2021-03-04T00:00:00Z","timestamp":1614816000000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0"}],"funder":[{"DOI":"10.13039\/100009619","name":"Japan Agency for Medical Research and Development","doi-asserted-by":"publisher","award":["JP20fk0108160"],"award-info":[{"award-number":["JP20fk0108160"]}],"id":[{"id":"10.13039\/100009619","id-type":"DOI","asserted-by":"publisher"}]},{"name":"Japan Health Research Promotion Bureau Research Fund"}],"content-domain":{"domain":["link.springer.com"],"crossmark-restriction":false},"short-container-title":["Sci Rep"],"abstract":"<jats:title>Abstract<\/jats:title><jats:p>The quantitative range and reproducibility of current serological tests for severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) are not optimized. Herein, we developed a diagnostic test that detects SARS-CoV-2 IgG and IgM with high quantitativeness and reproducibility and low interference. The system was based on the high-sensitivity chemiluminescence enzyme immunoassay (HISCL) platform and detects IgG and IgM specific to SARS-CoV-2 spike and nucleocapsid proteins. Quantification accuracy and reproducibility were evaluated using serially diluted samples from 60 SARS-CoV-2-infected patients. Assay performance was evaluated using serum samples from the SARS-CoV-2-infected patients and 500 SARS-CoV-2-negative serum samples collected before the emergence of SARS-CoV-2. The system showed high quantification accuracy (range, 10<jats:sup>2<\/jats:sup>), high reproducibility (within 5%), and no cross-reaction between SARS1- and MERS-S proteins. Detection accuracy was 98.3% and 93.3% for IgG and IgM against spike proteins and 100% and 71.7% for IgG and IgM against nucleocapsid proteins, respectively. Mean antibody levels were\u2009&gt;\u200910 times that in negative samples upon admission and\u2009&gt;\u2009100 times that at convalescent periods. Clinical severity upon admission was not correlated with IgG or IgM levels. This highly quantitative, reproducible assay system with high clinical performance may help analyze temporal serological\/immunological profiles of SARS-CoV-2 infection and SARS-CoV-2 vaccine effectiveness.<\/jats:p>","DOI":"10.1038\/s41598-021-84387-3","type":"journal-article","created":{"date-parts":[[2021,3,4]],"date-time":"2021-03-04T11:04:29Z","timestamp":1614855869000},"update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":62,"title":["A novel highly quantitative and reproducible assay for the detection of anti-SARS-CoV-2 IgG and IgM antibodies"],"prefix":"10.1038","volume":"11","author":[{"given":"Kenta","family":"Noda","sequence":"first","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Kouki","family":"Matsuda","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Shigehiro","family":"Yagishita","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Kenji","family":"Maeda","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Yutaro","family":"Akiyama","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Junko","family":"Terada-Hirashima","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Hiromichi","family":"Matsushita","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Satoshi","family":"Iwata","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Kazuto","family":"Yamashita","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Yusuke","family":"Atarashi","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Shunsuke","family":"Watanabe","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Nobuyuki","family":"Ide","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Tomokazu","family":"Yoshida","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Norio","family":"Ohmagari","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Hiroaki","family":"Mitsuya","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Akinobu","family":"Hamada","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"297","published-online":{"date-parts":[[2021,3,4]]},"reference":[{"key":"84387_CR1","doi-asserted-by":"publisher","first-page":"270","DOI":"10.1038\/s41586-020-2012-7","volume":"579","author":"P Zhou","year":"2020","unstructured":"Zhou, P. et al. A pneumonia outbreak associated with a new coronavirus of probable bat origin. Nature 579, 270\u2013273 (2020).","journal-title":"Nature"},{"key":"84387_CR2","doi-asserted-by":"publisher","first-page":"727","DOI":"10.1056\/NEJMoa2001017","volume":"382","author":"N Zhu","year":"2020","unstructured":"Zhu, N. et al. A novel coronavirus from patients with pneumonia in China, 2019. N. Engl. J. Med. 382, 727\u2013733 (2020).","journal-title":"N. Engl. J. Med."},{"key":"84387_CR3","unstructured":"World Health Organization. Coronavirus disease (COVID-19) outbreak situation. https:\/\/www.who.int\/emergencies\/diseases\/novel-coronavirus-2019 (Accessed June 2020)."},{"key":"84387_CR4","doi-asserted-by":"publisher","first-page":"1199","DOI":"10.1056\/NEJMoa2001316","volume":"382","author":"Q Li","year":"2020","unstructured":"Li, Q. et al. Early transmission dynamics in Wuhan, China, of novel coronavirus-infected pneumonia. N. Engl. J. Med. 382, 1199\u20131207 (2020).","journal-title":"N. Engl. J. Med."},{"key":"84387_CR5","doi-asserted-by":"publisher","first-page":"549","DOI":"10.1093\/clinchem\/hvaa029","volume":"66","author":"DKW Chu","year":"2020","unstructured":"Chu, D. K. W. et al. Molecular diagnosis of a novel coronavirus (2019-nCoV) causing an outbreak of pneumonia. Clin. Chem. 66, 549\u2013555 (2020).","journal-title":"Clin. Chem."},{"key":"84387_CR6","doi-asserted-by":"publisher","first-page":"977","DOI":"10.1093\/clinchem\/hvaa099","volume":"66","author":"X Wang","year":"2020","unstructured":"Wang, X. et al. Limits of detection of 6 approved RT-PCR kits for the novel SARS-coronavirus-2 (SARS-CoV-2). Clin. Chem. 66, 977\u2013979 (2020).","journal-title":"Clin. Chem."},{"key":"84387_CR7","doi-asserted-by":"publisher","DOI":"10.1093\/clinchem\/hvaa213","author":"AF Ogata","year":"2020","unstructured":"Ogata, A. F. et al. Ultra-sensitive serial profiling of SARS-CoV-2 antigens and antibodies in plasma to understand disease progression in COVID-19 patients with severe disease. Clin. Chem. https:\/\/doi.org\/10.1093\/clinchem\/hvaa213 (2020).","journal-title":"Clin. Chem."},{"key":"84387_CR8","doi-asserted-by":"publisher","first-page":"7264","DOI":"10.4049\/jimmunol.0903490","volume":"186","author":"F Tang","year":"2011","unstructured":"Tang, F. et al. Lack of peripheral memory B cell responses in recovered patients with severe acute respiratory syndrome: A six-year follow-up study. J. Immunol. 186, 7264\u20137268 (2011).","journal-title":"J. Immunol."},{"key":"84387_CR9","doi-asserted-by":"publisher","first-page":"665","DOI":"10.1128\/CDLI.11.4.665-668.2004","volume":"11","author":"PC Woo","year":"2004","unstructured":"Woo, P. C. et al. Longitudinal profile of immunoglobulin G (IgG), IgM, and IgA antibodies against the severe acute respiratory syndrome (SARS) coronavirus nucleocapsid protein in patients with pneumonia due to the SARS coronavirus. Clin. Diagn. Lab. Immunol. 11, 665\u2013668 (2004).","journal-title":"Clin. Diagn. Lab. Immunol."},{"key":"84387_CR10","doi-asserted-by":"publisher","first-page":"146","DOI":"10.1128\/CVI.00360-06","volume":"14","author":"F Yu","year":"2007","unstructured":"Yu, F. et al. Recombinant truncated nucleocapsid protein as antigen in a novel immunoglobulin M capture enzyme-linked immunosorbent assay for diagnosis of severe acute respiratory syndrome coronavirus infection. Clin. Vaccine Immunol. 14, 146\u2013149 (2007).","journal-title":"Clin. Vaccine Immunol."},{"key":"84387_CR11","doi-asserted-by":"publisher","first-page":"417","DOI":"10.1128\/CDLI.11.2.417-422.2004","volume":"11","author":"Q He","year":"2004","unstructured":"He, Q. et al. Development of a Western blot assay for detection of antibodies against coronavirus causing severe acute respiratory syndrome. Clin. Diagn. Lab. Immunol. 11, 417\u2013422 (2004).","journal-title":"Clin. Diagn. Lab. Immunol."},{"key":"84387_CR12","doi-asserted-by":"publisher","first-page":"2306","DOI":"10.1128\/JCM.42.5.2306-2309.2004","volume":"42","author":"PC Woo","year":"2004","unstructured":"Woo, P. C. et al. Detection of specific antibodies to severe acute respiratory syndrome (SARS) coronavirus nucleocapsid protein for serodiagnosis of SARS coronavirus pneumonia. J. Clin. Microbiol. 42, 2306\u20132309 (2004).","journal-title":"J. Clin. Microbiol."},{"key":"84387_CR13","doi-asserted-by":"publisher","first-page":"565","DOI":"10.1016\/S1473-3099(20)30196-1","volume":"20","author":"KK To","year":"2020","unstructured":"To, K. K. et al. Temporal profiles of viral load in posterior oropharyngeal saliva samples and serum antibody responses during infection by SARS-CoV-2: An observational cohort study. Lancet Infect. Dis. 20, 565\u2013574 (2020).","journal-title":"Lancet Infect. Dis."},{"key":"84387_CR14","doi-asserted-by":"publisher","first-page":"778","DOI":"10.1093\/cid\/ciaa310","volume":"71","author":"L Guo","year":"2020","unstructured":"Guo, L. et al. Profiling early humoral response to diagnose novel coronavirus disease (COVID-19). Clin. Infect. Dis. 71, 778\u2013785 (2020).","journal-title":"Clin. Infect. Dis."},{"key":"84387_CR15","doi-asserted-by":"publisher","first-page":"104511","DOI":"10.1016\/j.jcv.2020.104511","volume":"129","author":"T Nicol","year":"2020","unstructured":"Nicol, T. et al. Assessment of SARS-CoV-2 serological tests for the diagnosis of COVID-19 through the evaluation of three immunoassays: Two automated immunoassays (Euroimmun and Abbott) and one rapid lateral flow immunoassay (NG Biotech). J. Clin. Virol. 129, 104511 (2020).","journal-title":"J. Clin. Virol."},{"key":"84387_CR16","doi-asserted-by":"publisher","first-page":"16561","DOI":"10.1038\/s41598-020-73491-5","volume":"10","author":"A Algaissi","year":"2020","unstructured":"Algaissi, A. et al. SARS-CoV-2 S1 and N-based serological assays reveal rapid seroconversion and induction of specific antibody response in COVID-19 patients. Sci. Rep. 10, 16561 (2020).","journal-title":"Sci. Rep."},{"key":"84387_CR17","doi-asserted-by":"publisher","first-page":"1055","DOI":"10.1093\/clinchem\/hvaa120","volume":"66","author":"MS Tang","year":"2020","unstructured":"Tang, M. S. et al. Clinical performance of two SARS-CoV-2 serologic assays. Clin. Chem. 66, 1055\u20131062 (2020).","journal-title":"Clin. Chem."},{"key":"84387_CR18","doi-asserted-by":"publisher","DOI":"10.1093\/clinchem\/hvaa211","author":"MS Tang","year":"2020","unstructured":"Tang, M. S. et al. Association between SARS-CoV-2 neutralizing antibodies and commercial serological assays. Clin. Chem. https:\/\/doi.org\/10.1093\/clinchem\/hvaa211 (2020).","journal-title":"Clin. Chem."},{"key":"84387_CR19","doi-asserted-by":"publisher","first-page":"eabd4250","DOI":"10.1126\/science.abd4250","volume":"370","author":"E Shrock","year":"2020","unstructured":"Shrock, E. et al. Viral epitope profiling of COVID-19 patients reveals cross-reactivity and correlates of severity. Science 370, eabd4250 (2020).","journal-title":"Science"},{"key":"84387_CR20","doi-asserted-by":"publisher","first-page":"293","DOI":"10.1093\/ajcp\/aqaa112","volume":"154","author":"AP Espejo","year":"2020","unstructured":"Espejo, A. P. et al. Review of current advances in serologic testing for COVID-19. Am. J. Clin. Pathol. 154, 293\u2013304 (2020).","journal-title":"Am. J. Clin. Pathol."},{"key":"84387_CR21","doi-asserted-by":"publisher","first-page":"845","DOI":"10.1038\/s41591-020-0897-1","volume":"26","author":"QX Long","year":"2020","unstructured":"Long, Q. X. et al. Antibody responses to SARS-CoV-2 in patients with COVID-19. Nat. Med. 26, 845\u2013848 (2020).","journal-title":"Nat. Med."},{"key":"84387_CR22","doi-asserted-by":"publisher","first-page":"940","DOI":"10.1080\/22221751.2020.1762515","volume":"9","author":"B Sun","year":"2020","unstructured":"Sun, B. et al. Kinetics of SARS-CoV-2 specific IgM and IgG responses in COVID-19 patients. Emerg. Microbes Infect. 9, 940\u2013948 (2020).","journal-title":"Emerg. Microbes Infect."},{"key":"84387_CR23","doi-asserted-by":"publisher","first-page":"e00461-20","DOI":"10.1128\/JCM.00461-20","volume":"58","author":"W Liu","year":"2020","unstructured":"Liu, W. et al. Evaluation of nucleocapsid and spike protein-based enzyme-linked immunosorbent assays for detecting antibodies against SARS-CoV-2. J. Clin. Microbiol. 58, e00461-20 (2020).","journal-title":"J. Clin. Microbiol."},{"key":"84387_CR24","doi-asserted-by":"publisher","first-page":"79","DOI":"10.1016\/j.cca.2020.05.047","volume":"509","author":"C Bundschuh","year":"2020","unstructured":"Bundschuh, C. et al. Evaluation of the EDI enzyme linked immunosorbent assays for the detection of SARS-CoV-2 IgM and IgG antibodies in human plasma. Clin. Chim. Acta 509, 79\u201382 (2020).","journal-title":"Clin. Chim. Acta"},{"key":"84387_CR25","doi-asserted-by":"publisher","first-page":"1518","DOI":"10.1002\/jmv.25727","volume":"92","author":"Z Li","year":"2020","unstructured":"Li, Z. et al. Development and clinical application of a rapid IgM\u2013IgG combined antibody test for SARS-CoV-2 infection diagnosis. J. Med. Virol. 92, 1518\u20131524. https:\/\/doi.org\/10.1002\/jmv.25727 (2020).","journal-title":"J. Med. Virol."},{"key":"84387_CR26","doi-asserted-by":"publisher","first-page":"e251","DOI":"10.1515\/cclm-2020-1042","volume":"58","author":"G Lippi","year":"2020","unstructured":"Lippi, G. et al. Preliminary evaluation of Roche Cobas Elecsys Anti-SARS-CoV-2 chemiluminescence immunoassay. Clin. Chem. Lab. Med. 58, e251\u2013e253 (2020).","journal-title":"Clin. Chem. Lab. Med."},{"key":"84387_CR27","doi-asserted-by":"publisher","first-page":"e00941","DOI":"10.1128\/JCM.00941-20","volume":"58","author":"A Bryan","year":"2020","unstructured":"Bryan, A. et al. Performance characteristics of the Abbott Architect SARS-CoV-2 IgG assay and seroprevalence in Boise, Idaho. Clin. Microbiol. 58, e00941-e1020 (2020).","journal-title":"Clin. Microbiol."},{"key":"84387_CR28","first-page":"417","volume":"50","author":"DW Jekarl","year":"2020","unstructured":"Jekarl, D. W. et al. Analytical and clinical evaluation of chemiluminescent carcinoembryonic antigen (CEA) by HISCL-5000 immunoanalyzer. Ann. Clin. Lab. Sci. 50, 417\u2013422 (2020).","journal-title":"Ann. Clin. Lab. Sci."},{"key":"84387_CR29","doi-asserted-by":"publisher","first-page":"652","DOI":"10.1128\/CVI.00078-16","volume":"23","author":"S Feng","year":"2016","unstructured":"Feng, S. et al. Evaluation of the novel HISCL chemiluminescence enzyme immunoassay for laboratory screening of hepatitis C virus. Clin. Vaccine Immunol. 23, 652\u2013654 (2016).","journal-title":"Clin. Vaccine Immunol."},{"key":"84387_CR30","doi-asserted-by":"publisher","first-page":"1033","DOI":"10.1038\/s41591-020-0913-5","volume":"26","author":"F Amanat","year":"2020","unstructured":"Amanat, F. et al. A serological assay to detect SARS-CoV-2 seroconversion in humans. Nat. Med. 26, 1033\u20131036 (2020).","journal-title":"Nat. Med."},{"key":"84387_CR31","doi-asserted-by":"publisher","DOI":"10.1101\/2020.04.10.036418v1","author":"BD Quinlan","year":"2020","unstructured":"Quinlan, B. D. et al. The SARS-CoV-2 receptor-binding domain elicits a potent neutralizing response without antibody-dependent enhancement. bioRxiv https:\/\/doi.org\/10.1101\/2020.04.10.036418v1 (2020).","journal-title":"bioRxiv"},{"key":"84387_CR32","doi-asserted-by":"publisher","first-page":"914","DOI":"10.1016\/j.cell.2020.04.011","volume":"181","author":"D Kim","year":"2020","unstructured":"Kim, D. et al. The architecture of SARS-CoV-2 transcriptome. Cell 181, 914-921.e10 (2020).","journal-title":"Cell"},{"key":"84387_CR33","doi-asserted-by":"publisher","first-page":"466","DOI":"10.1016\/j.tim.2004.08.008","volume":"12","author":"H Hofmann","year":"2004","unstructured":"Hofmann, H. & P\u00f6hlmann, S. Cellular entry of the SARS coronavirus. Trends Microbiol. 12, 466\u2013472 (2004).","journal-title":"Trends Microbiol."},{"key":"84387_CR34","doi-asserted-by":"publisher","DOI":"10.1101\/2020.07.27.222943v1","author":"JT Ladner","year":"2020","unstructured":"Ladner, J. T. et al. Epitope-resolved profiling of the SARS-CoV-2 antibody response identifies cross-reactivity with an endemic human CoV. bioRxiv https:\/\/doi.org\/10.1101\/2020.07.27.222943v1 (2020).","journal-title":"bioRxiv"},{"key":"84387_CR35","doi-asserted-by":"publisher","first-page":"671","DOI":"10.1016\/j.chom.2020.03.002","volume":"27","author":"A Grifoni","year":"2020","unstructured":"Grifoni, A. et al. A sequence homology and bioinformatic approach can predict candidate targets for immune responses to SARS-CoV-2. Cell Host Microbe 27, 671-680.e2 (2020).","journal-title":"Cell Host Microbe"},{"key":"84387_CR36","doi-asserted-by":"publisher","DOI":"10.1101\/2020.09.01.20182220v2","author":"S Klompus","year":"2020","unstructured":"Klompus, S. et al. Cross-reactive antibody responses against SARS-CoV-2 and seasonal common cold coronaviruses. medRxiv https:\/\/doi.org\/10.1101\/2020.09.01.20182220v2 (2020).","journal-title":"medRxiv"},{"key":"84387_CR37","doi-asserted-by":"publisher","DOI":"10.1002\/rmv.2162","author":"EO Murchu","year":"2020","unstructured":"Murchu, E. O. et al. Immune response following infection with SARS-CoV-2 and other coronaviruses: A rapid review. Rev. Med. Virol. https:\/\/doi.org\/10.1002\/rmv.2162 (2020).","journal-title":"Rev. Med. Virol."},{"key":"84387_CR38","doi-asserted-by":"publisher","DOI":"10.1007\/s15010-020-01503-7","author":"D Peterhoff","year":"2020","unstructured":"Peterhoff, D. et al. A highly specific and sensitive serological assay detects SARS-CoV-2 antibody levels in COVID-19 patients that correlate with neutralization. Infection https:\/\/doi.org\/10.1007\/s15010-020-01503-7 (2020).","journal-title":"Infection"},{"key":"84387_CR39","doi-asserted-by":"publisher","first-page":"82","DOI":"10.4103\/ijmr.IJMR_2382_20","volume":"152","author":"GR Deshpande","year":"2020","unstructured":"Deshpande, G. R. et al. Neutralizing antibody responses to SARS-CoV-2 in COVID-19 patients. Indian J. Med. Res. 152, 82\u201387 (2020).","journal-title":"Indian J. Med. Res."},{"key":"84387_CR40","doi-asserted-by":"publisher","first-page":"1073","DOI":"10.1038\/s41587-020-0631-z","volume":"38","author":"CW Tan","year":"2020","unstructured":"Tan, C. W. et al. A SARS-CoV-2 surrogate virus neutralization test based on antibody-mediated blockage of ACE2-spike protein-protein interaction. Nat. Biotechnol. 38, 1073\u20131078 (2020).","journal-title":"Nat. Biotechnol."},{"key":"84387_CR41","doi-asserted-by":"publisher","first-page":"4908","DOI":"10.4049\/jimmunol.174.8.4908","volume":"174","author":"Y He","year":"2005","unstructured":"He, Y., Lu, H., Siddiqui, P., Zhou, Y. & Jiang, S. Receptor-binding domain of severe acute respiratory syndrome coronavirus spike protein contains multiple conformation-dependent epitopes that induce highly potent neutralizing antibodies. J. Immunol. 174, 4908\u20134915 (2005).","journal-title":"J. Immunol."}],"container-title":["Scientific Reports"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.nature.com\/articles\/s41598-021-84387-3.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/www.nature.com\/articles\/s41598-021-84387-3","content-type":"text\/html","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/www.nature.com\/articles\/s41598-021-84387-3.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2022,12,3]],"date-time":"2022-12-03T04:54:39Z","timestamp":1670043279000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.nature.com\/articles\/s41598-021-84387-3"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2021,3,4]]},"references-count":41,"journal-issue":{"issue":"1","published-online":{"date-parts":[[2021,12]]}},"alternative-id":["84387"],"URL":"https:\/\/doi.org\/10.1038\/s41598-021-84387-3","relation":{},"ISSN":["2045-2322"],"issn-type":[{"value":"2045-2322","type":"electronic"}],"subject":[],"published":{"date-parts":[[2021,3,4]]},"assertion":[{"value":"30 November 2020","order":1,"name":"received","label":"Received","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"12 February 2021","order":2,"name":"accepted","label":"Accepted","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"4 March 2021","order":3,"name":"first_online","label":"First Online","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"KN, KY, YA, SW, NI, and TY are salaried employees of Sysmex Corporation. AH. and HMi have received research grants from Sysmex Corporation. The other authors declare no potential conflict of interest.","order":1,"name":"Ethics","group":{"name":"EthicsHeading","label":"Competing interests"}}],"article-number":"5198"}}