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SARS-CoV-2 Serologic Assays Dependent on Dual-Antigen Binding Demonstrate Diverging Kinetics Relative to Other
Elitza S Theel1, Patrick W Johnson2, Katie L Kunze3
1Department of Laboratory Medicine and Pathology, Mayo Clinicgrid.66875.3a, Rochester, Minnesota, USA.
Journal of Clinical Microbiology
|June 24, 2021
Summary
Antibody detection after COVID-19 depends on the assay used. While most tests show declining severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) antibody levels, some Roche assays reveal stable or increasing titers over 120 days.
Area of Science:
- Immunology
- Infectious Diseases
- Biochemistry
Background:
- Conflicting results exist regarding the durability of the anti-severe acute respiratory syndrome coronavirus 2 (anti-SARS-CoV-2) humoral immune response.
- Discrepancies may stem from varied patient cohorts, non-standardized methods, and assays measuring different humoral response aspects.
Purpose of the Study:
- To longitudinally assess severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) antibody profiles in convalescent plasma donors.
- To compare the performance of eight different commercially available serologic assays over 120 days post-symptom onset.
Main Methods:
- Serial measurement of SARS-CoV-2 antibodies in 44 convalescent plasma donors over 120 days.
- Utilized eight distinct assays varying in antigen source, antibody isotype detection, and measured activity (binding, blocking, neutralizing).
- Focused on assays with Food and Drug Administration emergency use authorization.
Main Results:
- Most assays indicated a gradual decline in antibody titers over 120 days.
- Two Roche electrochemiluminescence immunoassay assays (nucleocapsid and spike-based) showed stable or increasing antibody titers.
- Dual-antigen binding in Roche assays may contribute to sustained antibody detection.
Conclusions:
- SARS-CoV-2 antibody detection is highly dependent on the specific serologic assay employed.
- Assay methodology significantly impacts the interpretation of humoral immune response durability.
- Findings have implications for the clinical utility and future application of serologic assays for COVID-19.

