{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,2,17]],"date-time":"2026-02-17T17:45:12Z","timestamp":1771350312977,"version":"3.50.1"},"reference-count":46,"publisher":"MDPI AG","issue":"8","license":[{"start":{"date-parts":[[2022,7,28]],"date-time":"2022-07-28T00:00:00Z","timestamp":1658966400000},"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>Background: During the last two years, a variety of assays for the serological detection of antibodies to the new SARS-CoV-2 virus have been launched and used as part of standard care in many laboratories. The pace with which these tests have been introduced into routine care emphasizes the importance of quality measures for analytical methods, particularly with regard to the implications of results for clinical and epidemiologic decisions. Accuracy, reliability and comparability of analytical test results are thus essential, and here external quality assessment (EQA) is the most important quality assurance tool. It allows us to achieve harmonization of test methods as a prerequisite for a high standard of performance for laboratory and analytical techniques and their interpretation. Methods: This EQA scheme consisted of pre-characterized clinical biospecimens dedicated to the analysis of anti-SARS-CoV-2 IgG total antibodies and differentiation into spike protein-specific IgG antibodies against SARS-CoV-2 (anti-S-SARS-CoV-2) and nucleocapsid-specific IgG antibodies against SARS-CoV-2 (anti-N-SARS-CoV-2). Results: A total of 239 laboratories across Europe participated in this scheme, called CoVimm. In detail, 536 results for anti-SARS-CoV-2 IgG, 431 results for anti-S-SARS-CoV-2 IgG, and 200 results for anti-N-SARS-CoV-2 IgG were reported. Based on the pre-defined thresholds, the success rates for the determination of anti-S-SARS-CoV-2 IgG and anti-N-SARS-CoV-2 IgG were 96% and 90%, respectively. Interestingly, only 64% of the participating laboratories successfully passed the EQA scheme for the determination of total anti-SARS-CoV-2 IgG. Conclusions: This EQA revealed serious concerns regarding the reliability and appropriate use of anti-SARS-CoV-2 antibody assays in routine care. In addition to the wide heterogeneity of different assays used by participating laboratories, a lack of standardization and harmonization is also evident. This is of particular importance for reliable and clinically meaningful interpretation of test results.<\/jats:p>","DOI":"10.3390\/v14081662","type":"journal-article","created":{"date-parts":[[2022,7,29]],"date-time":"2022-07-29T01:41:16Z","timestamp":1659058876000},"page":"1662","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":8,"title":["Results of a European-Wide External Quality Assessment (EQA) Scheme for Serological Detection of Anti-SARS-CoV-2 (CoVimm)\u2014Pitfalls of Routine Application"],"prefix":"10.3390","volume":"14","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-2580-5038","authenticated-orcid":false,"given":"Maximilian","family":"Kittel","sequence":"first","affiliation":[{"name":"Department of Clinical Chemistry, University Medical Centre Mannheim, Medical Faculty Mannheim, University of Heidelberg, 68167 Mannheim, Germany"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Romy","family":"Eichner","sequence":"additional","affiliation":[{"name":"Department of Clinical Chemistry, University Medical Centre Mannheim, Medical Faculty Mannheim, University of Heidelberg, 68167 Mannheim, Germany"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Sihem","family":"Aida","sequence":"additional","affiliation":[{"name":"Department of Clinical Chemistry, University Medical Centre Mannheim, Medical Faculty Mannheim, University of Heidelberg, 68167 Mannheim, Germany"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Anna","family":"Bode","sequence":"additional","affiliation":[{"name":"Reference Institute for Bioanalytics, Stiftung f\u00fcr Pathobiochemie und Molekulare Diagnostik, 53175 Bonn, Germany"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Volker","family":"Ast","sequence":"additional","affiliation":[{"name":"Department of Clinical Chemistry, University Medical Centre Mannheim, Medical Faculty Mannheim, University of Heidelberg, 68167 Mannheim, Germany"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Anja","family":"Kessler","sequence":"additional","affiliation":[{"name":"Reference Institute for Bioanalytics, Stiftung f\u00fcr Pathobiochemie und Molekulare Diagnostik, 53175 Bonn, Germany"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Michael","family":"Neumaier","sequence":"additional","affiliation":[{"name":"Department of Clinical Chemistry, University Medical Centre Mannheim, Medical Faculty Mannheim, University of Heidelberg, 68167 Mannheim, Germany"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-8756-7821","authenticated-orcid":false,"given":"Roman","family":"W\u00f6lfel","sequence":"additional","affiliation":[{"name":"Bundeswehr Institute of Microbiology, 80937 Munich, Germany"},{"name":"German Center for Infection Research (DZIF), Partner Site Munich, 80333 Munich, Germany"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-8380-6581","authenticated-orcid":false,"given":"Verena","family":"Haselmann","sequence":"additional","affiliation":[{"name":"Department of Clinical Chemistry, University Medical Centre Mannheim, Medical Faculty Mannheim, University of Heidelberg, 68167 Mannheim, Germany"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"1968","published-online":{"date-parts":[[2022,7,28]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"140","DOI":"10.15585\/mmwr.mm6905e1","article-title":"Initial public health response and interim clinical guidance for the 2019 novel coronavirus outbreak\u2014United States, 31 December 2019\u20134 February 2020","volume":"69","author":"Patel","year":"2020","journal-title":"Morb. Mortal. Wkly. Rep."},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"2996","DOI":"10.1093\/cid\/ciaa742","article-title":"The laboratory diagnosis of coronavirus disease 2019\u2014Frequently asked questions","volume":"71","author":"Fang","year":"2020","journal-title":"Clin. Infect. Dis."},{"key":"ref_3","first-page":"CD013652","article-title":"Antibody tests for identification of current and past infection with SARS-CoV-2","volume":"6","author":"Deeks","year":"2020","journal-title":"Cochrane Database Syst. Rev."},{"key":"ref_4","doi-asserted-by":"crossref","first-page":"e00797-20","DOI":"10.1128\/JCM.00797-20","article-title":"The role of antibody testing for SARS-CoV-2: Is there one?","volume":"58","author":"Theel","year":"2020","journal-title":"J. Clin. Microbiol."},{"key":"ref_5","doi-asserted-by":"crossref","first-page":"e235","DOI":"10.1016\/S2666-5247(21)00266-4","article-title":"WHO International Standard for evaluation of the antibody response to COVID-19 vaccines: Call for urgent action by the scientific community","volume":"3","author":"Knezevic","year":"2021","journal-title":"Lancet Microbe"},{"key":"ref_6","doi-asserted-by":"crossref","first-page":"1786","DOI":"10.4081\/jphr.2020.1786","article-title":"COVID-19 pandemic: Emerging perspectives and future trends","volume":"9","author":"Tabish","year":"2020","journal-title":"J. Public Health Res."},{"key":"ref_7","doi-asserted-by":"crossref","first-page":"171","DOI":"10.1038\/s41579-020-00461-z","article-title":"Considerations for diagnostic COVID-19 tests","volume":"19","author":"Vandenberg","year":"2021","journal-title":"Nat. Rev. Microbiol."},{"key":"ref_8","doi-asserted-by":"crossref","first-page":"590","DOI":"10.1016\/j.ijid.2020.12.003","article-title":"Clinical evaluation of commercial automated SARS-CoV-2 immunoassays","volume":"103","author":"Kittel","year":"2021","journal-title":"Int. J. Infect. Dis."},{"key":"ref_9","unstructured":"Cdcgov (2022, May 13). Interim Guidelines for COVID-19 Antibody Testing|CDC, Available online: https:\/\/www.cdc.gov\/coronavirus\/2019-ncov\/lab\/resources\/antibody-tests-guidelines.html."},{"key":"ref_10","doi-asserted-by":"crossref","first-page":"e175","DOI":"10.1515\/cclm-2020-1554","article-title":"SARS-CoV-2 serologic tests: Do not forget the good laboratory practice","volume":"59","author":"Aloisio","year":"2021","journal-title":"Clin. Chem. Lab. Med."},{"key":"ref_11","doi-asserted-by":"crossref","first-page":"1589","DOI":"10.1515\/cclm-2016-0081","article-title":"Statistical approach for optimization of external quality assurance (EQA) studies of molecular and serological viral diagnostics","volume":"54","author":"Rumer","year":"2016","journal-title":"Clin. Chem. Lab. Med."},{"key":"ref_12","doi-asserted-by":"crossref","first-page":"87","DOI":"10.1016\/j.cccn.2004.02.037","article-title":"Quality specifications in EQA schemes: From theory to practice","volume":"346","author":"Sciacovelli","year":"2004","journal-title":"Clin. Chim. Acta"},{"key":"ref_13","doi-asserted-by":"crossref","first-page":"2121","DOI":"10.1515\/cclm-2020-1183","article-title":"Results of the first pilot external quality assessment (EQA) scheme for anti-SARS-CoV2-antibody testing","volume":"58","author":"Haselmann","year":"2020","journal-title":"Clin. Chem Lab. Med."},{"key":"ref_14","doi-asserted-by":"crossref","first-page":"e00559-21","DOI":"10.1128\/JCM.00559-21","article-title":"Assessing the quality of serological testing in the COVID-19 pandemic: Results of a European external quality assessment (EQA) scheme for Anti-SARS-CoV-2 antibody detection","volume":"59","author":"Ast","year":"2021","journal-title":"J. Clin. Microbiol."},{"key":"ref_15","unstructured":"Bioanalytik, R.F. (2022, June 29). Ringversuche Corona-Antik\u00f6rper 2022. Available online: https:\/\/www.rfb.bio\/cgi\/surveyDetails?rv_type=CoVimm&rvTypeForDetails=CoVimm&year=2022&rv_num=2&analyte=all&searchType=rv_type."},{"key":"ref_16","doi-asserted-by":"crossref","first-page":"593","DOI":"10.1021\/acssensors.0c02621","article-title":"COVID-19 antibody tests and their limitations","volume":"6","author":"Liu","year":"2021","journal-title":"ACS Sens."},{"key":"ref_17","doi-asserted-by":"crossref","first-page":"e3042","DOI":"10.1093\/cid\/ciaa1382","article-title":"The limit of detection matters: The case for benchmarking severe acute respiratory syndrome coronavirus 2 testing","volume":"73","author":"Arnaout","year":"2021","journal-title":"Clin. Infect. Dis."},{"key":"ref_18","unstructured":"AFP (2020). Antibody Tests Key to Ending COVID-19 Lockdowns-France 24, AFP."},{"key":"ref_19","doi-asserted-by":"crossref","first-page":"100119","DOI":"10.1016\/j.lanepe.2021.100119","article-title":"Mass SARS-CoV-2 serological screening, a population-based study in the Principality of Andorra","volume":"5","author":"Vilanova","year":"2021","journal-title":"Lancet Reg. Health Eur."},{"key":"ref_20","doi-asserted-by":"crossref","unstructured":"Gray, N., Calleja, D., Wimbush, A., Miralles-Dolz, E., Gray, A., De Angelis, M., Derrer-Merk, E., Oparaji, B.U., Stepanov, V., and Clearkin, L. (2020). Is \u201cno test is better than a bad test\u201d? Impact of diagnostic uncertainty in mass testing on the spread of COVID-19. PLoS ONE, 15.","DOI":"10.1101\/2020.04.16.20067884"},{"key":"ref_21","unstructured":"Shearer, M., Lucia Mullen, M., and Tom Inglesby, M. (2022). Developing A National Strategy for Serology (Antibody Testing), The Johns Hopkins Center for Health Security."},{"key":"ref_22","doi-asserted-by":"crossref","first-page":"5491","DOI":"10.1038\/s41598-021-84173-1","article-title":"Predictive values, uncertainty, and interpretation of serology tests for the novel coronavirus","volume":"11","author":"Brownstein","year":"2021","journal-title":"Sci. Rep."},{"key":"ref_23","unstructured":"Abutaleb, J.A.A.Y. (2021). Coronavirus Risk Calculations Get Harder as A Study Suggests Rapid Tests May Be Less Effective at Detecting Omicron, The Washington Post."},{"key":"ref_24","unstructured":"Todd Haugh, S.B. (2020). Opinion | Just Because You Test Positive for Antibodies Doesn\u2019t Mean You Have Them, The New York Times."},{"key":"ref_25","unstructured":"Mandavilli, A. (2020). Your Coronavirus Test Is Positive. Maybe It Shouldn\u2019t Be, The New York Times."},{"key":"ref_26","unstructured":"Abbott (2022, May 15). SARS-CoV-2-Immunassay|Core Laboratory bei Abbott. Available online: https:\/\/www.corelaboratory.abbott\/int\/de\/offerings\/segments\/infectious-disease\/sars-cov-2-."},{"key":"ref_27","doi-asserted-by":"crossref","first-page":"1938","DOI":"10.1128\/JCM.40.6.1938-1946.2002","article-title":"Multicenter evaluation of a new automated fourth-generation human immunodeficiency virus screening assay with a sensitive antigen detection module and high specificity","volume":"40","author":"Weber","year":"2002","journal-title":"J. Clin. Microbiol."},{"key":"ref_28","doi-asserted-by":"crossref","first-page":"e00227","DOI":"10.1016\/j.plabm.2021.e00227","article-title":"Diagnostic performance of an automated chemiluminescence immunoassay for SARS-CoV-2 IgG and IgM antibodies detection: A real life experience","volume":"25","author":"Villalta","year":"2021","journal-title":"Pract. Lab. Med."},{"key":"ref_29","unstructured":"CLSI (2022, March 15). Proficiency Testing & Medical Laboratory Quality-CLSI. Available online: https:\/\/clsi.org\/about\/blog\/using-proficiency-testing-to-improve-medical-laboratory-quality\/."},{"key":"ref_30","unstructured":"U.S. Food & Drug Administration (2022, May 10). Emergency Use Authorization|FDA, Available online: https:\/\/www.fda.gov\/emergency-preparedness-and-response\/mcm-legal-regulatory-and-policy-framework\/emergency-use-authorization."},{"key":"ref_31","doi-asserted-by":"crossref","first-page":"2001223","DOI":"10.2807\/1560-7917.ES.2020.25.27.2001223","article-title":"International external quality assessment for SARS-CoV-2 molecular detection and survey on clinical laboratory preparedness during the COVID-19 pandemic, April\/May 2020","volume":"25","author":"Matheeussen","year":"2020","journal-title":"Eurosurveillance"},{"key":"ref_32","unstructured":"Editors, H.C. (2022, May 10). First Confirmed Case of COVID-19 Found in U.S.-HISTORY. Available online: https:\/\/www.history.com\/this-day-in-history\/first-confirmed-case-of-coronavirus-found-in-us-washington-state."},{"key":"ref_33","doi-asserted-by":"crossref","first-page":"1878","DOI":"10.1515\/cclm-2021-0662","article-title":"Serological diagnostic for SARS-CoV-2: An experimental external quality assessment scheme","volume":"59","author":"Sciacovelli","year":"2021","journal-title":"Clin. Chem. Lab. Med."},{"key":"ref_34","doi-asserted-by":"crossref","first-page":"21","DOI":"10.1111\/imcb.12397","article-title":"Antibody detection assays for COVID-19 diagnosis: An early overview","volume":"99","author":"Ejazi","year":"2021","journal-title":"Immunol. Cell Biol."},{"key":"ref_35","doi-asserted-by":"crossref","first-page":"e02596-20","DOI":"10.1128\/JCM.02596-20","article-title":"Comparison of 16 serological SARS-CoV-2 immunoassays in 16 clinical laboratories","volume":"59","author":"Harritshoj","year":"2021","journal-title":"J. Clin. Microbiol."},{"key":"ref_36","doi-asserted-by":"crossref","first-page":"803","DOI":"10.1002\/jmv.26303","article-title":"Analytical and clinical validation of an ELISA for specific SARS-CoV-2 IgG, IgA, and IgM antibodies","volume":"93","author":"Wilmet","year":"2021","journal-title":"J. Med. Virol."},{"key":"ref_37","unstructured":"Roche Diagnostics (2022, June 29). Elecsys\u00ae Anti-SARS-CoV-2. Available online: https:\/\/diagnostics.roche.com\/global\/en\/products\/params\/elecsys-anti-sars-cov-2.html."},{"key":"ref_38","doi-asserted-by":"crossref","first-page":"e0024721","DOI":"10.1128\/Spectrum.00247-21","article-title":"Anti-spike protein assays to determine SARS-CoV-2 antibody levels: A head-to-head comparison of five quantitative assays","volume":"9","author":"Perkmann","year":"2021","journal-title":"Microbiol. Spectr."},{"key":"ref_39","doi-asserted-by":"crossref","first-page":"633184","DOI":"10.3389\/fimmu.2021.633184","article-title":"Antibody responses in COVID-19: A review","volume":"12","author":"Patino","year":"2021","journal-title":"Front. Immunol."},{"key":"ref_40","doi-asserted-by":"crossref","unstructured":"Beck, E.J., Hsieh, Y.H., Fernandez, R.E., Dashler, G., Egbert, E.R., Truelove, S.A., Garliss, C., Wang, R., Bloch, E.M., and Shrestha, R. (2021). Differentiation of SARS-CoV-2 naturally infected and vaccinated individuals in an inner-city emergency department. medRxiv, 21264968.","DOI":"10.1101\/2021.10.13.21264968"},{"key":"ref_41","doi-asserted-by":"crossref","first-page":"220","DOI":"10.1515\/cclm-2017-0283","article-title":"Results of the first external quality assessment scheme (EQA) for isolation and analysis of circulating tumour DNA (ctDNA)","volume":"56","author":"Haselmann","year":"2018","journal-title":"Clin. Chem. Lab. Med. (CCLM)"},{"key":"ref_42","doi-asserted-by":"crossref","first-page":"103101","DOI":"10.1016\/j.ebiom.2020.103101","article-title":"Analytical and clinical performances of five immunoassays for the detection of SARS-CoV-2 antibodies in comparison with neutralization activity","volume":"62","author":"Padoan","year":"2020","journal-title":"EBioMedicine"},{"key":"ref_43","doi-asserted-by":"crossref","first-page":"2001","DOI":"10.1515\/cclm-2020-1413","article-title":"IFCC interim guidelines on serological testing of antibodies against SARS-CoV-2","volume":"58","author":"Bohn","year":"2020","journal-title":"Clin. Chem. Lab. Med."},{"key":"ref_44","unstructured":"NIBSC (2022, May 03). COVID-19-Related Research Reagents, Available online: https:\/\/www.nibsc.org\/science_and_research\/idd\/cfar\/covid-19_reagents.aspx."},{"key":"ref_45","unstructured":"Commission, R.-J.S.H.-E. (2022, May 03). Welcome to the Certified Reference Materials catalogue of the JRC. Available online: https:\/\/crm.jrc.ec.europa.eu\/?ref=1."},{"key":"ref_46","doi-asserted-by":"crossref","first-page":"1670","DOI":"10.1373\/clinchem.2011.168641","article-title":"Proficiency testing\/external quality assessment: Current challenges and future directions","volume":"57","author":"Miller","year":"2011","journal-title":"Clin. Chem."}],"container-title":["Viruses"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.mdpi.com\/1999-4915\/14\/8\/1662\/pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,10,10]],"date-time":"2025-10-10T23:58:33Z","timestamp":1760140713000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.mdpi.com\/1999-4915\/14\/8\/1662"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2022,7,28]]},"references-count":46,"journal-issue":{"issue":"8","published-online":{"date-parts":[[2022,8]]}},"alternative-id":["v14081662"],"URL":"https:\/\/doi.org\/10.3390\/v14081662","relation":{},"ISSN":["1999-4915"],"issn-type":[{"value":"1999-4915","type":"electronic"}],"subject":[],"published":{"date-parts":[[2022,7,28]]}}}