SARS-CoV-2–Specific Antibody Detection for Seroepidemiology: A Multiplex Analysis Approach Accounting for Accurate Seroprevalence
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Abstract
Background: The COVID-19 pandemic necessitates better understanding of the kinetics of antibody production induced by infection with SARS-CoV-2. We aimed to develop a high-throughput multiplex assay to detect antibodies to SARS-CoV-2 to assess immunity to the virus in the general population. Methods: Spike protein subunits S1 and receptor binding domain, and nucleoprotein were coupled to microspheres. Sera collected before emergence of SARS-CoV-2 (n = 224) and of non-SARS-CoV-2 influenza-like illness (n = 184), and laboratory-confirmed cases of SARS-CoV-2 infection (n = 115) with various severities of COVID-19 were tested for SARS-CoV-2–specific IgG concentrations. Results: Our assay discriminated SARS-CoV-2–induced antibodies and those induced by other viruses. The assay specificity was 95.1%–99.0% with sensitivity 83.6%–95.7%. By merging the test results for all 3 antigens a specificity of 100% was achieved with a sensitivity of at least 90%. Hospitalized COVID-19 patients developed higher IgG concentrations and the rate of IgG production increased faster compared to nonhospitalized cases. Conclusions: The bead-based serological assay for quantitation of SARS-CoV-2–specific antibodies proved to be robust and can be conducted in many laboratories. We demonstrated that testing of antibodies against multiple antigens increases sensitivity and specificity compared to single-antigen–specific IgG determination.
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The Luminex MIA allowed clear interpretation and quantitative comparison of antibody responses within groups and at different time points.
“The Luminex MIA, on the other hand, allowed clear interpretation and quantitative comparison of antibody responses within the groups and at different time points (45).”
From SARS-CoV-2 variants of concern partially escape humoral but not T cell responses in COVID-19 convalescent donors and vaccine recipients (2021) · cites this paper as [45]
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- Authors
- den Hartog, G., Schepp, R. M., Kuijer, M., GeurtsvanKessel, C., van Beek, J., Rots, N., Koopmans, M. P. G., van der Klis, F. R. M., & van Binnendijk, R. S.
- Affiliations
- Centre for Immunology of Infectious Diseases and Vaccines, National Institute for Public Health and the Environment, Bilthoven, the Netherlands
- National Institute for Public Health and the Environment (NL)
- Erasmus MC (NL)
- ORCID
- Venue
- The Journal of Infectious Diseases
- Publisher
- Oxford University Press (OUP)
- Published
- 2020-08-08
- Volume
- 222
- Issue
- 9
- Pages
- 1452-1461
- ISSN
- 0022-1899 (ISSN-L)
- 1537-6613
- PMC
- PMC7454740
- OpenAlex
- W3048274045
- Cited by
- 137
- References
- 25
- Citations by year
- 2026: 1 · 2025: 7 · 2024: 30 · 2023: 18 · 2022: 31 · 2021: 37 · 2020: 13
- FWCI
- 3.24
- Type
- journal article
- Language
- en
- Open access
- hybrid
- doi.org
- Licence
- Locations
- The Journal of Infectious Diseases (publishedVersion, cc-by-nc-nd)
- medRxiv (acceptedVersion, cc-by-nc-nd)
- PubMed Central (publishedVersion, cc-by-nc-nd)
- PubMed (publishedVersion)
- EUR Research Repository (Erasmus University Rotterdam) (publishedVersion, other-oa)
- EUR Research Repository (Erasmus University Rotterdam) (submittedVersion, other-oa)
- RePub (Erasmus University Rotterdam) (submittedVersion, other-oa)
- Rivm (National Institute for Public Health and the Environment) (submittedVersion)
- Rivm (National Institute for Public Health and the Environment) (submittedVersion, other-oa)
- Funders
- National Institute for Public Health and the Environment
- Topics
- Health Sciences › Medicine › Infectious Diseases › SARS-CoV-2 and COVID-19 Research
- Health Sciences › Medicine › Infectious Diseases › SARS-CoV-2 detection and testing
- Health Sciences › Medicine › Infectious Diseases › COVID-19 Clinical Research Studies
- Keywords
- SARS-CoV-2, COVID-19 pandemic, seroepidemiology, seroprevalence, multiplex bead immunoassay, SARS-CoV-2 antibodies, IgG quantification, spike protein S1, receptor binding domain, nucleocapsid protein, assay sensitivity and specificity, COVID-19 severity, antibody kinetics
- MeSH terms
- Seroconversion, Betacoronavirus, COVID-19, SARS-CoV-2, Adult, Aged, Aged, 80 and over, Antibodies, Viral, Female, Humans, Immunoglobulin G, Immunoassay, Male, Middle Aged, Netherlands, Nuclear Proteins, Pneumonia, Viral, ROC Curve, Case-Control Studies, Seroepidemiologic Studies, Coronavirus Infections, Area Under Curve, Adaptive Immunity, Pandemics, Patient Acuity, Spike Glycoprotein, Coronavirus
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