{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,22]],"date-time":"2026-10-22T09:22:55Z","timestamp":1792660975635,"version":"4.5.0"},"reference-count":27,"publisher":"MDPI AG","issue":"5","license":[{"start":{"date-parts":[[2021,4,24]],"date-time":"2021-04-24T00:00:00Z","timestamp":1619222400000},"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>The emerging SARS-CoV-2 pandemic entails an urgent need for specific and sensitive high-throughput serological assays to assess SARS-CoV-2 epidemiology. We, therefore, aimed at developing a fluorescent-bead based SARS-CoV-2 multiplex serology assay for detection of antibody responses to the SARS-CoV-2 proteome. Proteins of the SARS-CoV-2 proteome and protein N of SARS-CoV-1 and common cold Coronaviruses (ccCoVs) were recombinantly expressed in E. coli or HEK293 cells. Assay performance was assessed in a COVID-19 case cohort (n = 48 hospitalized patients from Heidelberg) as well as n = 85 age- and sex-matched pre-pandemic controls from the ESTHER study. Assay validation included comparison with home-made immunofluorescence and commercial enzyme-linked immunosorbent (ELISA) assays. A sensitivity of 100% (95% CI: 86\u2013100%) was achieved in COVID-19 patients 14 days post symptom onset with dual sero-positivity to SARS-CoV-2 N and the receptor-binding domain of the spike protein. The specificity obtained with this algorithm was 100% (95% CI: 96\u2013100%). Antibody responses to ccCoVs N were abundantly high and did not correlate with those to SARS-CoV-2 N. Inclusion of additional SARS-CoV-2 proteins as well as separate assessment of immunoglobulin (Ig) classes M, A, and G allowed for explorative analyses regarding disease progression and course of antibody response. This newly developed SARS-CoV-2 multiplex serology assay achieved high sensitivity and specificity to determine SARS-CoV-2 sero-positivity. Its high throughput ability allows epidemiologic SARS-CoV-2 research in large population-based studies. Inclusion of additional pathogens into the panel as well as separate assessment of Ig isotypes will furthermore allow addressing research questions beyond SARS-CoV-2 sero-prevalence.<\/jats:p>","DOI":"10.3390\/v13050749","type":"journal-article","created":{"date-parts":[[2021,4,25]],"date-time":"2021-04-25T02:12:57Z","timestamp":1619316777000},"page":"749","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":21,"title":["From Multiplex Serology to Serolomics\u2014A Novel Approach to the Antibody Response against the SARS-CoV-2 Proteome"],"prefix":"10.3390","volume":"13","author":[{"given":"Julia","family":"Butt","sequence":"first","affiliation":[{"name":"Infections and Cancer Epidemiology, German Cancer Research Center (Deutsches Krebsforschungszentrum, DKFZ), 69120 Heidelberg, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-0336-7268","authenticated-orcid":false,"given":"Rajagopal","family":"Murugan","sequence":"additional","affiliation":[{"name":"B Cell Immunology, German Cancer Research Center (Deutsches Krebsforschungszentrum, DKFZ), 69120 Heidelberg, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Theresa","family":"Hippchen","sequence":"additional","affiliation":[{"name":"Department of Internal Medicine IV, University Hospital Heidelberg, 69120 Heidelberg, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sylvia","family":"Olberg","sequence":"additional","affiliation":[{"name":"Department of Infectious Diseases, Virology, University Hospital Heidelberg, 69120 Heidelberg, Germany"},{"name":"German Center for Infection Research (DZIF), Heidelberg Partner Site, 69120 Heidelberg, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Monique","family":"van Straaten","sequence":"additional","affiliation":[{"name":"Division of Structural Biology of Infection and Immunity, German Cancer Research Center (Deutsches Krebsforschungszentrum, DKFZ), 69120 Heidelberg, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Hedda","family":"Wardemann","sequence":"additional","affiliation":[{"name":"B Cell Immunology, German Cancer Research Center (Deutsches Krebsforschungszentrum, DKFZ), 69120 Heidelberg, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Erec","family":"Stebbins","sequence":"additional","affiliation":[{"name":"Division of Structural Biology of Infection and Immunity, German Cancer Research Center (Deutsches Krebsforschungszentrum, DKFZ), 69120 Heidelberg, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-8756-329X","authenticated-orcid":false,"given":"Hans-Georg","family":"Kr\u00e4usslich","sequence":"additional","affiliation":[{"name":"Department of Infectious Diseases, Virology, University Hospital Heidelberg, 69120 Heidelberg, Germany"},{"name":"German Center for Infection Research (DZIF), Heidelberg Partner Site, 69120 Heidelberg, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ralf","family":"Bartenschlager","sequence":"additional","affiliation":[{"name":"German Center for Infection Research (DZIF), Heidelberg Partner Site, 69120 Heidelberg, Germany"},{"name":"Department of Infectious Diseases, Molecular Virology, Heidelberg University, 69120 Heidelberg, Germany"},{"name":"Division Virus-Associated Carcinogenesis, German Cancer Research Center (DKFZ), 69120 Heidelberg, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-6129-1572","authenticated-orcid":false,"given":"Hermann","family":"Brenner","sequence":"additional","affiliation":[{"name":"Division of Clinical Epidemiology and Aging Research, German Cancer Research Center (Deutsches Krebsforschungszentrum, DKFZ), 69120 Heidelberg, Germany"},{"name":"Network Aging Research, University of Heidelberg, 69120 Heidelberg, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Vibor","family":"Laketa","sequence":"additional","affiliation":[{"name":"Department of Infectious Diseases, Virology, University Hospital Heidelberg, 69120 Heidelberg, Germany"},{"name":"German Center for Infection Research (DZIF), Heidelberg Partner Site, 69120 Heidelberg, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-1217-4521","authenticated-orcid":false,"given":"Ben","family":"Sch\u00f6ttker","sequence":"additional","affiliation":[{"name":"Division of Clinical Epidemiology and Aging Research, German Cancer Research Center (Deutsches Krebsforschungszentrum, DKFZ), 69120 Heidelberg, Germany"},{"name":"Network Aging Research, University of Heidelberg, 69120 Heidelberg, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-5726-5585","authenticated-orcid":false,"given":"Barbara","family":"M\u00fcller","sequence":"additional","affiliation":[{"name":"Department of Infectious Diseases, Virology, University Hospital Heidelberg, 69120 Heidelberg, 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