Characterization of a Pan-Immunoglobulin Assay Quantifying Antibodies Directed against the Receptor Binding Domain of the SARS-CoV-2 S1-Subunit of the Spike Protein: A Population-Based Study
Pan-immunoglobulin assays can simultaneously detect IgG, IgM and IgA directed against the receptor binding domain (RBD) of the S1 subunit of the spike protein (S) of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2 S1-RBD Ig). In this work, we aim to evaluate a quantitative SARS-CoV-2 S1-...
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| Language: | English |
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MDPI AG
2020-12-01
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| Series: | Journal of Clinical Medicine |
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| Online Access: | https://www.mdpi.com/2077-0383/9/12/3989 |
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| author | Anna Schaffner Lorenz Risch Stefanie Aeschbacher Corina Risch Myriam C. Weber Sarah L. Thiel Katharina Jüngert Michael Pichler Kirsten Grossmann Nadia Wohlwend Thomas Lung Dorothea Hillmann Susanna Bigler Thomas Bodmer Mauro Imperiali Harald Renz Philipp Kohler Pietro Vernazza Christian R. Kahlert Raphael Twerenbold Matthias Paprotny David Conen Martin Risch |
| author_facet | Anna Schaffner Lorenz Risch Stefanie Aeschbacher Corina Risch Myriam C. Weber Sarah L. Thiel Katharina Jüngert Michael Pichler Kirsten Grossmann Nadia Wohlwend Thomas Lung Dorothea Hillmann Susanna Bigler Thomas Bodmer Mauro Imperiali Harald Renz Philipp Kohler Pietro Vernazza Christian R. Kahlert Raphael Twerenbold Matthias Paprotny David Conen Martin Risch |
| author_sort | Anna Schaffner |
| collection | DOAJ |
| description | Pan-immunoglobulin assays can simultaneously detect IgG, IgM and IgA directed against the receptor binding domain (RBD) of the S1 subunit of the spike protein (S) of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2 S1-RBD Ig). In this work, we aim to evaluate a quantitative SARS-CoV-2 S1-RBD Ig electrochemiluminescence immunoassay (ECLIA) regarding analytical, diagnostic, operational and clinical characteristics. Our work takes the form of a population-based study in the principality of Liechtenstein, including 125 cases with clinically well-described and laboratory confirmed SARS-CoV-2 infection and 1159 individuals without evidence of coronavirus disease 2019 (COVID-19). SARS-CoV-2 cases were tested for antibodies in sera taken with a median of 48 days (interquartile range, IQR, 43–52) and 139 days (IQR, 129–144) after symptom onset. Sera were also tested with other assays targeting antibodies against non-RBD-S1 and -S1/S2 epitopes. Sensitivity was 97.6% (95% confidence interval, CI, 93.2–99.1), whereas specificity was 99.8% (95% CI, 99.4–99.9). Antibody levels linearly decreased from hospitalized patients to symptomatic outpatients and SARS-CoV-2 infection without symptoms (<i>p</i> < 0.001). Among cases with SARS-CoV-2 infection, smokers had lower antibody levels than non-smokers (<i>p</i> = 0.04), and patients with fever had higher antibody levels than patients without fever (<i>p</i> = 0.001). Pan-SARS-CoV-2 S1-RBD Ig in SARS-CoV-2 infection cases significantly increased from first to second follow-up (<i>p</i> < 0.001). A substantial proportion of individuals without evidence of past SARS-CoV-2 infection displayed non-S1-RBD antibody reactivities (248/1159, i.e., 21.4%, 95% CI, 19.1–23.4). In conclusion, a quantitative SARS-CoV-2 S1-RBD Ig assay offers favorable and sustained assay characteristics allowing the determination of quantitative associations between clinical characteristics (e.g., disease severity, smoking or fever) and antibody levels. The assay could also help to identify individuals with antibodies of non-S1-RBD specificity with potential clinical cross-reactivity to SARS-CoV-2. |
| first_indexed | 2024-03-10T14:13:02Z |
| format | Article |
| id | doaj.art-c0d5282dcba3437dab6da6009c1103b4 |
| institution | Directory Open Access Journal |
| issn | 2077-0383 |
| language | English |
| last_indexed | 2024-03-10T14:13:02Z |
| publishDate | 2020-12-01 |
| publisher | MDPI AG |
| record_format | Article |
| series | Journal of Clinical Medicine |
| spelling | doaj.art-c0d5282dcba3437dab6da6009c1103b42023-11-21T00:02:16ZengMDPI AGJournal of Clinical Medicine2077-03832020-12-01912398910.3390/jcm9123989Characterization of a Pan-Immunoglobulin Assay Quantifying Antibodies Directed against the Receptor Binding Domain of the SARS-CoV-2 S1-Subunit of the Spike Protein: A Population-Based StudyAnna Schaffner0Lorenz Risch1Stefanie Aeschbacher2Corina Risch3Myriam C. Weber4Sarah L. Thiel5Katharina Jüngert6Michael Pichler7Kirsten Grossmann8Nadia Wohlwend9Thomas Lung10Dorothea Hillmann11Susanna Bigler12Thomas Bodmer13Mauro Imperiali14Harald Renz15Philipp Kohler16Pietro Vernazza17Christian R. Kahlert18Raphael Twerenbold19Matthias Paprotny20David Conen21Martin Risch22Landesspital Liechtenstein, Heiligkreuz, 9490 Vaduz, LiechtensteinLabormedizinisches Zentrum Dr Risch, Wuhrstrasse 14, 9490 Vaduz, LiechtensteinCardiovascular Research Institute Basel (CRIB), University Hospital Basel, University of Basel, Spitalstrasse 2, 4056 Basel, SwitzerlandLabormedizinisches Zentrum Dr Risch, Wuhrstrasse 14, 9490 Vaduz, LiechtensteinLandesspital Liechtenstein, Heiligkreuz, 9490 Vaduz, LiechtensteinLandesspital Liechtenstein, Heiligkreuz, 9490 Vaduz, LiechtensteinLandesspital Liechtenstein, Heiligkreuz, 9490 Vaduz, LiechtensteinLandesspital Liechtenstein, Heiligkreuz, 9490 Vaduz, LiechtensteinLabormedizinisches Zentrum Dr Risch, Wuhrstrasse 14, 9490 Vaduz, LiechtensteinLabormedizinisches Zentrum Dr Risch, Wuhrstrasse 14, 9490 Vaduz, LiechtensteinLabormedizinisches Zentrum Dr Risch, Wuhrstrasse 14, 9490 Vaduz, LiechtensteinLabormedizinisches Zentrum Dr Risch, Wuhrstrasse 14, 9490 Vaduz, LiechtensteinLabormedizinisches Zentrum Dr Risch, Waldeggstrasse 37, 3097 Liebefeld, SwitzerlandLabormedizinisches Zentrum Dr Risch, Waldeggstrasse 37, 3097 Liebefeld, SwitzerlandCentro Medicina di Laboratorio Dr Risch, Via Arbostra 2, 6963 Pregassona, SwitzerlandInstitute of Laboratory Medicine and Pathobiochemistry, Molecular Diagnostics, University Hospital Giessen and Marburg, Philipps University Marburg, Baldingerstraße, 35043 Marburg, GermanyDepartment of Infectious Diseases and Hospital Epidemiology, Cantonal Hospital St. Gallen, Rohrschacherstrasse 95, 9007 St. Gallen, SwitzerlandDepartment of Infectious Diseases and Hospital Epidemiology, Cantonal Hospital St. Gallen, Rohrschacherstrasse 95, 9007 St. Gallen, SwitzerlandDepartment of Infectious Diseases and Hospital Epidemiology, Cantonal Hospital St. Gallen, Rohrschacherstrasse 95, 9007 St. Gallen, SwitzerlandCardiovascular Research Institute Basel (CRIB), University Hospital Basel, University of Basel, Spitalstrasse 2, 4056 Basel, SwitzerlandLandesspital Liechtenstein, Heiligkreuz, 9490 Vaduz, LiechtensteinPopulation Health Research Institute, McMaster University, 237 Barton Street East, Hamilton, ON L8L 2X2, CanadaCentral Laboratory, Kantonsspital Graubünden, Loësstrasse 170, 7000 Chur, SwitzerlandPan-immunoglobulin assays can simultaneously detect IgG, IgM and IgA directed against the receptor binding domain (RBD) of the S1 subunit of the spike protein (S) of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2 S1-RBD Ig). In this work, we aim to evaluate a quantitative SARS-CoV-2 S1-RBD Ig electrochemiluminescence immunoassay (ECLIA) regarding analytical, diagnostic, operational and clinical characteristics. Our work takes the form of a population-based study in the principality of Liechtenstein, including 125 cases with clinically well-described and laboratory confirmed SARS-CoV-2 infection and 1159 individuals without evidence of coronavirus disease 2019 (COVID-19). SARS-CoV-2 cases were tested for antibodies in sera taken with a median of 48 days (interquartile range, IQR, 43–52) and 139 days (IQR, 129–144) after symptom onset. Sera were also tested with other assays targeting antibodies against non-RBD-S1 and -S1/S2 epitopes. Sensitivity was 97.6% (95% confidence interval, CI, 93.2–99.1), whereas specificity was 99.8% (95% CI, 99.4–99.9). Antibody levels linearly decreased from hospitalized patients to symptomatic outpatients and SARS-CoV-2 infection without symptoms (<i>p</i> < 0.001). Among cases with SARS-CoV-2 infection, smokers had lower antibody levels than non-smokers (<i>p</i> = 0.04), and patients with fever had higher antibody levels than patients without fever (<i>p</i> = 0.001). Pan-SARS-CoV-2 S1-RBD Ig in SARS-CoV-2 infection cases significantly increased from first to second follow-up (<i>p</i> < 0.001). A substantial proportion of individuals without evidence of past SARS-CoV-2 infection displayed non-S1-RBD antibody reactivities (248/1159, i.e., 21.4%, 95% CI, 19.1–23.4). In conclusion, a quantitative SARS-CoV-2 S1-RBD Ig assay offers favorable and sustained assay characteristics allowing the determination of quantitative associations between clinical characteristics (e.g., disease severity, smoking or fever) and antibody levels. The assay could also help to identify individuals with antibodies of non-S1-RBD specificity with potential clinical cross-reactivity to SARS-CoV-2.https://www.mdpi.com/2077-0383/9/12/3989area under the curvecoronavirusCOVID-19diagnostic accuracyimmunoassaypredictive values |
| spellingShingle | Anna Schaffner Lorenz Risch Stefanie Aeschbacher Corina Risch Myriam C. Weber Sarah L. Thiel Katharina Jüngert Michael Pichler Kirsten Grossmann Nadia Wohlwend Thomas Lung Dorothea Hillmann Susanna Bigler Thomas Bodmer Mauro Imperiali Harald Renz Philipp Kohler Pietro Vernazza Christian R. Kahlert Raphael Twerenbold Matthias Paprotny David Conen Martin Risch Characterization of a Pan-Immunoglobulin Assay Quantifying Antibodies Directed against the Receptor Binding Domain of the SARS-CoV-2 S1-Subunit of the Spike Protein: A Population-Based Study Journal of Clinical Medicine area under the curve coronavirus COVID-19 diagnostic accuracy immunoassay predictive values |
| title | Characterization of a Pan-Immunoglobulin Assay Quantifying Antibodies Directed against the Receptor Binding Domain of the SARS-CoV-2 S1-Subunit of the Spike Protein: A Population-Based Study |
| title_full | Characterization of a Pan-Immunoglobulin Assay Quantifying Antibodies Directed against the Receptor Binding Domain of the SARS-CoV-2 S1-Subunit of the Spike Protein: A Population-Based Study |
| title_fullStr | Characterization of a Pan-Immunoglobulin Assay Quantifying Antibodies Directed against the Receptor Binding Domain of the SARS-CoV-2 S1-Subunit of the Spike Protein: A Population-Based Study |
| title_full_unstemmed | Characterization of a Pan-Immunoglobulin Assay Quantifying Antibodies Directed against the Receptor Binding Domain of the SARS-CoV-2 S1-Subunit of the Spike Protein: A Population-Based Study |
| title_short | Characterization of a Pan-Immunoglobulin Assay Quantifying Antibodies Directed against the Receptor Binding Domain of the SARS-CoV-2 S1-Subunit of the Spike Protein: A Population-Based Study |
| title_sort | characterization of a pan immunoglobulin assay quantifying antibodies directed against the receptor binding domain of the sars cov 2 s1 subunit of the spike protein a population based study |
| topic | area under the curve coronavirus COVID-19 diagnostic accuracy immunoassay predictive values |
| url | https://www.mdpi.com/2077-0383/9/12/3989 |
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