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A chip-based assay for detection and avidity assessment of SARS-CoV-2 antibodies in serum and saliva

The pathogenic virus SARS-CoV-2 has caused millions of infections and deaths from coronavirus disease 2019 (COVID-19) worldwide. Antibody-based testing of SARS-CoV-2 is crucial for detecting infections in resource-limited regions, as well as for assessing antibody levels needed for immunity and vaccine efficacy. However, current antibody tests based on immunosorbent ELISA and chemiluminescence CLIA technologies are prone to false positives and are unable to assess antibody avidity and maturation which can help distinguish recent versus old infections. Recent advances in nanotechnology have led to the use of plasmonic gold (pGOLD) substrates for antibody assays. This technology takes advantage of near-infrared (NIR) fluorescence for enhanced sensitivity and is capable of measuring antibody avidity.

In a recent publication in Nature Biomedical Engineering, Liu et al. report a pGOLD-based antibody assay for detection of IgG and IgM antibodies against SARS-CoV-2. The authors developed an optimized pGOLD slide with antigen spots for the S1 subunit of the spike protein and the receptor binding domain (RBD). Captured IgG and IgM antibodies were then labeled using anti-human IgG-IRDye800 and anti-human IgM-CF®647. The pGOLD chip was imaged using a confocal microscopy scanner to interpret results. To evaluate the assay, the authors tested ~500 negative and positive SARS-CoV-2 patient serum samples. The pGOLD SARS-CoV-2 assay was successful in detecting 100% of COVID-19 positive sera after 14 days of infection. An IgG avidity test was also validated with the assay showing a lower avidity for SARS-CoV-2 compared to more common human coronaviruses in patient samples collected between 6 and 45 days post infection. The authors note that a low avidity is expected due to the recent infection and a lack of immune memory for a completely new virus. Lastly, the authors tested the assay for detection of SARS-CoV-2 antibodies in human saliva. They found that the pGOLD assay was successful in differentiating between positive COVID-19 saliva samples and healthy controls. Overall, the authors demonstrate a promising pGOLD-based antibody assay for sensitive detection and avidity assessment of SARS-CoV-2 antibodies that could be used with non-invasive sample collection.

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Full Citation:

Liu, T., Hsiung, J., Zhao, S., Kost. et al. Quantification of antibody avidities and accurate detection of SARS-CoV-2 antibodies in serum and saliva on plasmonic substrates. Nature Biomedical Engineering 4:12, 4(12), 1188–1196 (2020).