Performance of the Abbott SARS-CoV-2 IgG II Quantitative Antibody Assay Including the New Variants of Concern, VOC 202012/V1 (United Kingdom) and VOC 202012/V2 (South Africa), and First Steps towards Global Harmonization of COVID-19 Antibody Methods

Abstract

In the initial stages of the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) COVID-19 pandemic, a plethora of new serology tests were developed and introduced to the global market. Many were not evaluated rigorously, and there is a significant lack of concordance in results across methods. To enable meaningful clinical decisions to be made, robustly evaluated, quantitative serology methods are needed. These should be harmonized to a primary reference material, allowing for the comparison of trial data and improved clinical decision making. A comprehensive evaluation of the new Abbott IgG II anti-SARS-CoV-2 IgG method was undertaken using CLSI-based protocols. Two different candidate primary reference materials and verification panels were assessed with a goal to move toward harmonization. The Abbott IgG II method performed well across a wide range of parameters with excellent imprecision (<3.5%) and was linear throughout the positive range (tested to 38,365 AU/ml). The sensitivity (based on ≥14-day post-positive reverse transcription-PCR [RT-PCR] samples) and specificity were 98.3% (90.6% to 100.0%) and 99.5% (97.1% to 100%), respectively. The candidate reference materials showed poor correlation across methods, with mixed responses noted in methods that use the spike protein versus the nucleocapsid proteins as their binding antigen. The Abbott IgG II anti-SARS-CoV-2 measurement appears to be the first linear method potentially capable of monitoring the immune response to natural infection, including from new emerging variants. The candidate reference materials assessed did not generate uniform results across several methods, and further steps are needed to enable the harmonization process.

Keywords: COVID-19; SARS-CoV-2; analytical performance; antibody assay; evaluation; harmonization; serology; variants.

FIG 1

Linearity of method over the complete working range of the Abbott IgG II assay using a range of dilutions of a high positive (mean, 38,365 AU/ml) in the Abbott diluent. Dash-dot line indicates the identity line. The darker dotted line represents the 95% likelihood asymmetrical CI of the slope.

FIG 2

Cohen’s kappa concordance analysis of the assays and overall (all samples included) agreement of results given as percent. Equivocal results were considered negative.

FIG 3

Representative examples of the quantitative immune response in three different variants of the SARS-CoV-2 virus, including the “UK” and “South Africa” variants. The days post-PCR do not necessarily correlate to the day of onset of symptoms or the day of hospitalization.

FIG 4

Comparison graphs of the values obtained for the Technopath positive panel with different methods: (A) Abbott IgG II versus DiaSorin Liaison XL; (B) Abbott IgG II versus EDI; (C) Abbott IgG II quantitative (S) versus Abbott IgG qualitative (R). Only the Abbott quantitative assay showed linearity (r² = 0.9984) and was plotted against DiaSorin, quadratic (r² = 0.9988) (A), EDI, 4-PL (r² = 0.9574) (B), and Abbott qualitative, 4-PL (r² = 0.9946) (C).

FIG 5

Dilution of NIBSC working standard 20/162 using the Abbott diluent. Dash-dot line indicates the identity line. The darker dotted line represents the 95% likelihood asymmetrical CI of the slope.