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Serological assays for the detection of SARS-CoV-2 infections are important to understand the immune response in patients and to obtain epidemiological data about the number of infected people, especially to identify asymptomatic persons not aware of a past infection.<\/jats:p>\n              <\/jats:sec><jats:sec>\n                <jats:title>Methods<\/jats:title>\n                <jats:p>We recombinantly produced SARS-CoV-2 nucleocapsid (N)-protein in <jats:italic>Escherichia coli<\/jats:italic>. We used the purified protein to develop an indirect enzyme-linked immunosorbent assay (ELISA) for the detection of SARS-CoV-2 specific antibodies. This ELISA method was optimized and validated with serum samples collected from 113 patients with RT-PCR-confirmed SARS-CoV-2 infections including hospitalized COVID-19 patients and 1500 control sera mostly collected before 2015 with different clinical background.<\/jats:p>\n              <\/jats:sec><jats:sec>\n                <jats:title>Results<\/jats:title>\n                <jats:p>The optimized N-protein-ELISA provided a sensitivity of 89.7% (n\u2009=\u200968) for samples collected from patients with confirmed SARS-CoV-2 infections and mild to severe symptoms more than 14\u00a0days after symptom onset or a positive PCR test. The antibody levels remained low for serum samples collected in the first six days (n\u2009=\u200923) and increased in the second week (n\u2009=\u200922) post symptom onset or PCR confirmation. At this early phase, the ELISA provided a sensitivity of 39.1% and 86.4%, respectively, reflecting the time of an IgG immune response against pathogens. The assay specificity was 99.3% (n\u2009=\u20091500; 95% CI 0.995\u20130.999). Serum samples from persons with confirmed antibody titers against human immunodeficiency viruses 1\/2, parvovirus B19, hepatitis A\/B virus, cytomegalovirus, Epstein Barr virus, and herpes simplex virus were tested negative.<\/jats:p>\n              <\/jats:sec><jats:sec>\n                <jats:title>Conclusions<\/jats:title>\n                <jats:p>We conclude that the N-protein-based ELISA developed here is well suited for the sensitive and specific serological detection of SARS-CoV-2 specific IgG antibodies in human serum for symptomatic infections. It may also prove useful to identify previous SARS-CoV-2 infections in vaccinated people, as all currently approved vaccines rely on the SARS-CoV-2 spike (S-) protein.<\/jats:p>\n              <\/jats:sec>","DOI":"10.1186\/s12985-022-01768-4","type":"journal-article","created":{"date-parts":[[2022,3,19]],"date-time":"2022-03-19T19:02:31Z","timestamp":1647716551000},"update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":40,"title":["Sensitive and specific serological ELISA for the detection of SARS-CoV-2 infections"],"prefix":"10.1186","volume":"19","author":[{"given":"Ji","family":"Luo","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Alexandra","family":"Brakel","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Andor","family":"Krizsan","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Tobias","family":"Ludwig","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Marina","family":"M\u00f6tzing","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Daniela","family":"Volke","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Nicole","family":"Lakowa","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-2955-3085","authenticated-orcid":false,"given":"Thomas","family":"Gr\u00fcnewald","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Claudia","family":"Lehmann","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Johannes","family":"Wolf","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Stephan","family":"Borte","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sanja","family":"Milkovska-Stamenova","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"J\u00f6rg","family":"Gabert","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Felix","family":"Fingas","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Markus","family":"Scholz","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-9932-5646","authenticated-orcid":false,"given":"Ralf","family":"Hoffmann","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"297","published-online":{"date-parts":[[2022,3,19]]},"reference":[{"issue":"7","key":"1768_CR1","doi-asserted-by":"publisher","first-page":"1033","DOI":"10.1038\/s41591-020-0913-5","volume":"26","author":"F Amanat","year":"2020","unstructured":"Amanat F, Stadlbauer D, Strohmeier S, Nguyen T, Chromikova V, McMahon M, et al. 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JL, SMS, and FF are employees of Adversis Pharma GmbH. JG is cofounder and CEO of Adversis Pharma GmbH. All other authors declare that they have no competing interests.","order":4,"name":"Ethics","group":{"name":"EthicsHeading","label":"Competing interests"}}],"article-number":"50"}}