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SARS-CoV-2-Specific Antibody Detection for Seroepidemiology: A Multiplex Analysis Approach Accounting for Accurate Seroprevalence.
J Infect Dis. 2020 10 01; 222(9):1452-1461.JI

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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Authors+Show Affiliations

den Hartog G
Centre for Immunology of Infectious Diseases and Vaccines, National Institute for Public Health and the Environment, Bilthoven, the Netherlands.
Schepp RM
Centre for Immunology of Infectious Diseases and Vaccines, National Institute for Public Health and the Environment, Bilthoven, the Netherlands.
Kuijer M
Centre for Immunology of Infectious Diseases and Vaccines, National Institute for Public Health and the Environment, Bilthoven, the Netherlands.
GeurtsvanKessel C
Department of Viroscience, Erasmus Medical Center, Rotterdam, the Netherlands.
van Beek J
Centre for Immunology of Infectious Diseases and Vaccines, National Institute for Public Health and the Environment, Bilthoven, the Netherlands.
Rots N
Centre for Immunology of Infectious Diseases and Vaccines, National Institute for Public Health and the Environment, Bilthoven, the Netherlands.
Koopmans MPG
Department of Viroscience, Erasmus Medical Center, Rotterdam, the Netherlands.
van der Klis FRM
Centre for Immunology of Infectious Diseases and Vaccines, National Institute for Public Health and the Environment, Bilthoven, the Netherlands.
van Binnendijk RS
Centre for Immunology of Infectious Diseases and Vaccines, National Institute for Public Health and the Environment, Bilthoven, the Netherlands.

MeSH

Adaptive ImmunityAdultAgedAged, 80 and overAntibodies, ViralArea Under CurveBetacoronavirusCOVID-19Case-Control StudiesCoronavirus InfectionsFemaleHumansImmunoassayImmunoglobulin GMaleMiddle AgedNetherlandsNuclear ProteinsPandemicsPatient AcuityPneumonia, ViralROC CurveSARS-CoV-2SeroconversionSeroepidemiologic StudiesSpike Glycoprotein, Coronavirus

Pub Type(s)

Journal Article
Research Support, Non-U.S. Gov't

Language

eng

PubMed ID

32766833

Citation

den Hartog, Gerco, et al. "SARS-CoV-2-Specific Antibody Detection for Seroepidemiology: a Multiplex Analysis Approach Accounting for Accurate Seroprevalence." The Journal of Infectious Diseases, vol. 222, no. 9, 2020, pp. 1452-1461.
den Hartog G, Schepp RM, Kuijer M, et al. SARS-CoV-2-Specific Antibody Detection for Seroepidemiology: A Multiplex Analysis Approach Accounting for Accurate Seroprevalence. J Infect Dis. 2020;222(9):1452-1461.
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. (2020). SARS-CoV-2-Specific Antibody Detection for Seroepidemiology: A Multiplex Analysis Approach Accounting for Accurate Seroprevalence. The Journal of Infectious Diseases, 222(9), 1452-1461. https://doi.org/10.1093/infdis/jiaa479
den Hartog G, et al. SARS-CoV-2-Specific Antibody Detection for Seroepidemiology: a Multiplex Analysis Approach Accounting for Accurate Seroprevalence. J Infect Dis. 2020 10 1;222(9):1452-1461. PubMed PMID: 32766833.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - SARS-CoV-2-Specific Antibody Detection for Seroepidemiology: A Multiplex Analysis Approach Accounting for Accurate Seroprevalence. AU - den Hartog,Gerco, AU - Schepp,Rutger M, AU - Kuijer,Marjan, AU - GeurtsvanKessel,Corine, AU - van Beek,Josine, AU - Rots,Nynke, AU - Koopmans,Marion P G, AU - van der Klis,Fiona R M, AU - van Binnendijk,Robert S, PY - 2020/06/02/received PY - 2020/07/30/accepted PY - 2020/8/9/pubmed PY - 2020/10/21/medline PY - 2020/8/9/entrez KW - COVID-19 KW - IgG KW - RBD KW - endemic coronavirus KW - influenza-like Illness (ILI) KW - multiplex bead-based immune assay KW - nucleoprotein KW - sensitivity KW - specificity KW - spike S1 SP - 1452 EP - 1461 JF - The Journal of infectious diseases JO - J Infect Dis VL - 222 IS - 9 N2 - 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. SN - 1537-6613 UR - https://www.unboundmedicine.com/medline/citation/32766833/SARS_CoV_2_Specific_Antibody_Detection_for_Seroepidemiology:_A_Multiplex_Analysis_Approach_Accounting_for_Accurate_Seroprevalence_ L2 - https://academic.oup.com/jid/article-lookup/doi/10.1093/infdis/jiaa479 DB - PRIME DP - Unbound Medicine ER -