Abstract
Sensitive and specific serological tests are mandatory for epidemiological studies evaluating severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) prevalence as well as coronavirus disease 2019 (COVID-19) morbidity and mortality rates. The accuracy of results is challenged by antibody waning after convalescence and by cross-reactivity induced by previous infections with other pathogens. By employing a patented platform technology based on capturing antigen-antibody complexes with a solid-phase-bound Fcγ receptor (FcγR) and truncated nucleocapsid protein as the antigen, two SARS-CoV-2 IgG enzyme-linked immunosorbent assays (ELISAs), featuring different serum and antigen dilutions, were developed. Validation was performed using a serum panel comprising 213 longitudinal samples from 35 COVID-19 patients and a negative-control panel consisting of 790 pre-COVID-19 samples from different regions of the world. While both assays show similar diagnostic sensitivities in the early convalescent phase, ELISA 2 (featuring a higher serum concentration) enables SARS-CoV-2 IgG antibody detection for a significantly longer time postinfection (≥15 months). Correspondingly, analytical sensitivity referenced to indirect immunofluorescence testing (IIFT) is significantly higher for ELISA 2 in samples with a titer of ≤1:640; for high-titer samples, a prozone effect is observed for ELISA 2. The specificities of both ELISAs were excellent not only for pre-COVID-19 serum samples from Europe, Asia, and South America but also for several challenging African sample panels. The SARS-CoV-2 IgG FcγR ELISAs, methodically combining antigen-antibody binding in solution and isotype-specific detection of immune complexes, are valuable tools for seroprevalence studies requiring the (long-term) detection of anti-SARS-CoV-2 IgG antibodies in populations with a challenging immunological background and/or in which spike-protein-based vaccine programs have been rolled out.
Keywords: immunoassay; immunoglobulins; infectious disease; laboratory methods and tools; viral diseases.
【저자키워드】 immunoglobulins, Infectious disease, immunoassay, Viral diseases, laboratory methods and tools, 【초록키워드】 COVID-19, coronavirus disease, serological test, SARS-CoV-2, Coronavirus disease 2019, Vaccine, coronavirus, Europe, antibody, immunoglobulins, Infection, diagnostic, Infectious disease, severe acute respiratory syndrome Coronavirus, ELISA, Population, nucleocapsid protein, Laboratory, Antigen, Immune complexes, Asia, cross-reactivity, Prevalence, immunoassay, serum, sensitivity, specificity, enzyme-linked immunosorbent assay, Region, validation, IgG antibody, Viral, Serological tests, Accuracy, anti-SARS-CoV-2 IgG, anti-SARS-CoV-2 IgG antibodies, enzyme-linked immunosorbent assays, SARS-CoV-2 IgG antibody, titer, African, morbidity, convalescence, Pathogens, morbidity and mortality, receptor, immunofluorescence, respiratory, sensitive, South America, mortality rates, Viral diseases, platform, ELISAs, SARS-CoV-2 IgG, antibody waning, binding, analytical sensitivity, Concentration, COVID-19 patient, indirect immunofluorescence, diagnostic sensitivities, acute respiratory syndrome, antigen-antibody complexes, solution, acute respiratory syndrome coronavirus, serum samples, acute respiratory syndrome coronavirus 2, convalescent phase, epidemiological studies, Epidemiological study, FcγR, Specificities, dilutions, while, serum sample, longitudinal samples, immunological, prozone, Postinfection, significantly, was performed, significantly higher, complexes, anti-SARS-CoV-2 IgG antibody, mandatory, 【제목키워드】 IgG, Human, detection, persistent, sensitive, Specific,