High-Accuracy Multiplexed SARS-CoV-2 Antibody Assay with Avidity and Saliva Capability on a Nano-Plasmonic Platform

Abstract

The outbreak and rapid spread of SARS-CoV-2 virus has led to a dire global pandemic with millions of people infected and ~ 400,000 deaths thus far. Highly accurate detection of antibodies for COVID-19 is an indispensable part of the effort to combat the pandemic 1,2 . Here we developed two-plex antibody detection against SARS-CoV-2 spike proteins 3 (the S1 subunit and receptor binding domain RBD) in human serum and saliva on a near-infrared nanoplasmonic gold (pGOLD) platform 4-8 . By testing nearly 600 serum samples, pGOLD COVID-19 assay achieved ~ 99.78 % specificity for detecting both IgG and IgM with 100 % sensitivity in sera collected > 14 days post disease symptom onset, with zero cross-reactivity to other diseases. Two-plex correlation analysis revealed higher binding of serum IgM to RBD than to S1. IgG antibody avidity toward multiple antigens were measured, shedding light on antibody maturation in COVID-19 patients and affording a powerful tool for differentiating recent from remote infections and identifying re-infection by SARS-CoV-2. Just as important, due to high analytical sensitivity, the pGOLD COVID-19 assay detected minute amounts of antibodies in human saliva, offering the first non-invasive detection of SARS-CoV-2 antibodies.

Vaccination versus infection with SARS‐CoV‐2: Establishment of a high avidity IgG response versus incomplete avidity maturation

“…An initial analysis revealed that avidity maturation after SARS‐CoV‐2 infection remained at an untypical low level in most cases 12 . This is in line with the reports by other groups 9,10,17–20 …”

“…These findings of incomplete avidity maturation after natural infection with SARS‐CoV‐2 are in line with the findings by several other groups. 9 , 10 , 17 , 18 , 19 , 20 Also, the study by Luo et al 24 is indirectly confirming this view, as Luo et al used 3 M urea. This resulted in an overestimation of avidity in comparison with the use of the discriminatory concentration of 7 M urea.…”

Clinical characteristics and antibody response to SARS-CoV-2 spike 1 protein using VITROS Anti-SARS-CoV-2 antibody tests in COVID-19 patients in Japan

“…Taken together, the IgG antibody assay is preferable to the total antibody assay for surveillance of COVID-19 seroprevalence. Liu et al [ 30 ] reported a strong correlation of the IgG titre against S1 with the RBD. Although further study is still needed to clarify the correlation of antibody titre determined by the VITROS Anti-SARS-CoV-2 antibody assays and neutralization antibody, the weight of evidence to date suggests that the VITROS Anti-SARS-CoV-2 antibody assays also may be used for the evaluation of humoral immunity against SARS-CoV-2.…”

“…AST (IU l −1 ) 30 27 [20][21][22][23][24][25][26][27][28][29][30][31][32][33] 55 <0.001 ** ALT (IU l −1 ) 31 27 utility of serological assays as supporting diagnostic tools and to understand the pathogenicity of SARS-CoV-2.…”

Clinical characteristics and antibody response to SARS-CoV-2 spike 1 protein using the VITROS Anti-SARS-CoV-2 antibody tests in COVID-19 patients in Japan

“…Liu et al reported a strong correlation of the IgG titer against S1 with the RBD. [27] Although further study is still needed to clarify the correlation of antibody titer determined by the VITROS Anti-SARS-CoV-2 antibody assays and neutralization antibody, the weight of evidence to date suggests that the VITROS Anti-SARS-CoV-2 antibody assays also may be used for the evaluation of humoral immunity against SARS-CoV-2.…”