Concordance of SARS-CoV-2 Antibody Results during a Period of Low Prevalence
ABSTRACT Accurate, highly specific immunoassays for severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) are needed to evaluate seroprevalence. This study investigated the concordance of results across four immunoassays targeting different antigens for sera collected at the beginning of the...
| Main Authors: | , , , , , , , , , , , , , , , , , , |
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| Format: | Article |
| Language: | English |
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American Society for Microbiology
2022-10-01
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| Series: | mSphere |
| Subjects: | |
| Online Access: | https://journals.asm.org/doi/10.1128/msphere.00257-22 |
| _version_ | 1811330030635057152 |
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| author | Cheryl N. Miller Keri N. Althoff David J. Schlueter Hoda Anton-Culver Qingxia Chen Shawn Garbett Francis Ratsimbazafy Isaac Thomsen Elizabeth W. Karlson Mine Cicek Ligia A. Pinto Bradley A. Malin Lucila Ohno-Machado Carolyn Williams David Goldstein Aymone Kouame Andrea Ramirez Kelly A. Gebo Sheri D. Schully |
| author_facet | Cheryl N. Miller Keri N. Althoff David J. Schlueter Hoda Anton-Culver Qingxia Chen Shawn Garbett Francis Ratsimbazafy Isaac Thomsen Elizabeth W. Karlson Mine Cicek Ligia A. Pinto Bradley A. Malin Lucila Ohno-Machado Carolyn Williams David Goldstein Aymone Kouame Andrea Ramirez Kelly A. Gebo Sheri D. Schully |
| author_sort | Cheryl N. Miller |
| collection | DOAJ |
| description | ABSTRACT Accurate, highly specific immunoassays for severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) are needed to evaluate seroprevalence. This study investigated the concordance of results across four immunoassays targeting different antigens for sera collected at the beginning of the SARS-CoV-2 pandemic in the United States. Specimens from All of Us participants contributed between January and March 2020 were tested using the Abbott Architect SARS-CoV-2 IgG (immunoglobulin G) assay (Abbott) and the EuroImmun SARS-CoV-2 enzyme-linked immunosorbent assay (ELISA) (EI). Participants with discordant results, participants with concordant positive results, and a subset of concordant negative results by Abbott and EI were also tested using the Roche Elecsys anti-SARS-CoV-2 (IgG) test (Roche) and the Ortho-Clinical Diagnostics Vitros anti-SARS-CoV-2 IgG test (Ortho). The agreement and 95% confidence intervals were estimated for paired assay combinations. SARS-CoV-2 antibody concentrations were quantified for specimens with at least two positive results across four immunoassays. Among the 24,079 participants, the percent agreement for the Abbott and EI assays was 98.8% (95% confidence interval, 98.7%, 99%). Of the 490 participants who were also tested by Ortho and Roche, the probability-weighted percentage of agreement (95% confidence interval) between Ortho and Roche was 98.4% (97.9%, 98.9%), that between EI and Ortho was 98.5% (92.9%, 99.9%), that between Abbott and Roche was 98.9% (90.3%, 100.0%), that between EI and Roche was 98.9% (98.6%, 100.0%), and that between Abbott and Ortho was 98.4% (91.2%, 100.0%). Among the 32 participants who were positive by at least 2 immunoassays, 21 had quantifiable anti-SARS-CoV-2 antibody concentrations by research assays. The results across immunoassays revealed concordance during a period of low prevalence. However, the frequency of false positivity during a period of low prevalence supports the use of two sequentially performed tests for unvaccinated individuals who are seropositive by the first test. IMPORTANCE What is the agreement of commercial SARS-CoV-2 immunoglobulin G (IgG) assays during a time of low coronavirus disease 2019 (COVID-19) prevalence and no vaccine availability? Serological tests produced concordant results in a time of low SARS-CoV-2 prevalence and no vaccine availability, driven largely by the proportion of samples that were negative by two immunoassays. The CDC recommends two sequential tests for positivity for future pandemic preparedness. In a subset analysis, quantified antinucleocapsid and antispike SARS-CoV-2 IgG antibodies do not suggest the need to specify the antigen targets of the sequential assays in the CDC’s recommendation because false positivity varied as much between assays targeting the same antigen as it did between assays targeting different antigens. |
| first_indexed | 2024-04-13T15:54:11Z |
| format | Article |
| id | doaj.art-7930847087474e8a85c0a61186606340 |
| institution | Directory Open Access Journal |
| issn | 2379-5042 |
| language | English |
| last_indexed | 2024-04-13T15:54:11Z |
| publishDate | 2022-10-01 |
| publisher | American Society for Microbiology |
| record_format | Article |
| series | mSphere |
| spelling | doaj.art-7930847087474e8a85c0a611866063402022-12-22T02:40:45ZengAmerican Society for MicrobiologymSphere2379-50422022-10-017510.1128/msphere.00257-22Concordance of SARS-CoV-2 Antibody Results during a Period of Low PrevalenceCheryl N. Miller0Keri N. Althoff1David J. Schlueter2Hoda Anton-Culver3Qingxia Chen4Shawn Garbett5Francis Ratsimbazafy6Isaac Thomsen7Elizabeth W. Karlson8Mine Cicek9Ligia A. Pinto10Bradley A. Malin11Lucila Ohno-Machado12Carolyn Williams13David Goldstein14Aymone Kouame15Andrea Ramirez16Kelly A. Gebo17Sheri D. Schully18Frederick National Laboratory for Cancer Research, National Cancer Institute, Frederick, Maryland, USADepartment of Epidemiology, Johns Hopkins Bloomberg School of Public Health, Baltimore, Maryland, USANational Human Genome Research Institute, National Institutes of Health, Bethesda, Maryland, USADepartment of Medicine, School of Medicine, University of California, Irvine, Irvine, California, USADepartment of Biomedical Informatics, Vanderbilt University Medical Center, Nashville, Tennessee, USADepartment of Biomedical Informatics, Vanderbilt University Medical Center, Nashville, Tennessee, USADepartment of Biomedical Informatics, Vanderbilt University Medical Center, Nashville, Tennessee, USADepartment of Pediatrics, Division of Infectious Diseases, Vanderbilt University Medical Center, Nashville, Tennessee, USAHarvard Medical School, Brigham and Women’s Hospital, Boston, Massachusetts, USAMayo Clinic, Rochester, Minnesota, USAFrederick National Laboratory for Cancer Research, National Cancer Institute, Frederick, Maryland, USADepartment of Biomedical Informatics, Vanderbilt University Medical Center, Nashville, Tennessee, USADepartment of Biomedical Informatics, University of California—San Diego Health, La Jolla, California, USANational Institute of Allergy and Infectious Disease, National Institutes of Health, Bethesda, Maryland, USAColumbia University Medical Center, New York, New York, USADepartment of Biomedical Informatics, Vanderbilt University Medical Center, Nashville, Tennessee, USAAll of Us Research Program, National Institutes of Health, Bethesda, Maryland, USADepartment of Medicine, Johns Hopkins University School of Medicine, Baltimore, Maryland, USAAll of Us Research Program, National Institutes of Health, Bethesda, Maryland, USAABSTRACT Accurate, highly specific immunoassays for severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) are needed to evaluate seroprevalence. This study investigated the concordance of results across four immunoassays targeting different antigens for sera collected at the beginning of the SARS-CoV-2 pandemic in the United States. Specimens from All of Us participants contributed between January and March 2020 were tested using the Abbott Architect SARS-CoV-2 IgG (immunoglobulin G) assay (Abbott) and the EuroImmun SARS-CoV-2 enzyme-linked immunosorbent assay (ELISA) (EI). Participants with discordant results, participants with concordant positive results, and a subset of concordant negative results by Abbott and EI were also tested using the Roche Elecsys anti-SARS-CoV-2 (IgG) test (Roche) and the Ortho-Clinical Diagnostics Vitros anti-SARS-CoV-2 IgG test (Ortho). The agreement and 95% confidence intervals were estimated for paired assay combinations. SARS-CoV-2 antibody concentrations were quantified for specimens with at least two positive results across four immunoassays. Among the 24,079 participants, the percent agreement for the Abbott and EI assays was 98.8% (95% confidence interval, 98.7%, 99%). Of the 490 participants who were also tested by Ortho and Roche, the probability-weighted percentage of agreement (95% confidence interval) between Ortho and Roche was 98.4% (97.9%, 98.9%), that between EI and Ortho was 98.5% (92.9%, 99.9%), that between Abbott and Roche was 98.9% (90.3%, 100.0%), that between EI and Roche was 98.9% (98.6%, 100.0%), and that between Abbott and Ortho was 98.4% (91.2%, 100.0%). Among the 32 participants who were positive by at least 2 immunoassays, 21 had quantifiable anti-SARS-CoV-2 antibody concentrations by research assays. The results across immunoassays revealed concordance during a period of low prevalence. However, the frequency of false positivity during a period of low prevalence supports the use of two sequentially performed tests for unvaccinated individuals who are seropositive by the first test. IMPORTANCE What is the agreement of commercial SARS-CoV-2 immunoglobulin G (IgG) assays during a time of low coronavirus disease 2019 (COVID-19) prevalence and no vaccine availability? Serological tests produced concordant results in a time of low SARS-CoV-2 prevalence and no vaccine availability, driven largely by the proportion of samples that were negative by two immunoassays. The CDC recommends two sequential tests for positivity for future pandemic preparedness. In a subset analysis, quantified antinucleocapsid and antispike SARS-CoV-2 IgG antibodies do not suggest the need to specify the antigen targets of the sequential assays in the CDC’s recommendation because false positivity varied as much between assays targeting the same antigen as it did between assays targeting different antigens.https://journals.asm.org/doi/10.1128/msphere.00257-22SARS-CoV-2IgG antibodiesspike proteinnucleocapsid proteinlow prevalence |
| spellingShingle | Cheryl N. Miller Keri N. Althoff David J. Schlueter Hoda Anton-Culver Qingxia Chen Shawn Garbett Francis Ratsimbazafy Isaac Thomsen Elizabeth W. Karlson Mine Cicek Ligia A. Pinto Bradley A. Malin Lucila Ohno-Machado Carolyn Williams David Goldstein Aymone Kouame Andrea Ramirez Kelly A. Gebo Sheri D. Schully Concordance of SARS-CoV-2 Antibody Results during a Period of Low Prevalence mSphere SARS-CoV-2 IgG antibodies spike protein nucleocapsid protein low prevalence |
| title | Concordance of SARS-CoV-2 Antibody Results during a Period of Low Prevalence |
| title_full | Concordance of SARS-CoV-2 Antibody Results during a Period of Low Prevalence |
| title_fullStr | Concordance of SARS-CoV-2 Antibody Results during a Period of Low Prevalence |
| title_full_unstemmed | Concordance of SARS-CoV-2 Antibody Results during a Period of Low Prevalence |
| title_short | Concordance of SARS-CoV-2 Antibody Results during a Period of Low Prevalence |
| title_sort | concordance of sars cov 2 antibody results during a period of low prevalence |
| topic | SARS-CoV-2 IgG antibodies spike protein nucleocapsid protein low prevalence |
| url | https://journals.asm.org/doi/10.1128/msphere.00257-22 |
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