Evaluation of five widely used serologic assays for antibodies to SARS-CoV-2

Christopher Stocking, Laura de Miguel, Gabriela Suteu, Alexander Dressel, Andrea Soricelli, Martin Roskos, Santiago Valor, Caren Mutschmann, Winfried März, Christopher Stocking, Laura de Miguel, Gabriela Suteu, Alexander Dressel, Andrea Soricelli, Martin Roskos, Santiago Valor, Caren Mutschmann, Winfried März

Abstract

Reliable diagnostic technologies are pivotal to the fight against COVID-19. While real-time reverse transcription-polymerase chain reaction (rRT-PCR) remains the gold standard, commercial assays for antibodies against (SARS-CoV-2) have emerged. We sought to examine 5 widely used commercial methods. We measured antibodies against SARS-CoV-2 with assays, Abbott-IgG, Roche-IgT (total antibodies, isotype-unspecific), EUROIMMUN-IgG, EUROIMMUN-IgA, DiaSorin-IgG, in 191 serum samples from patients with rRT-PCR proven COVID-19 between days 0 and 47 after the onset of clinical symptoms and in biobank samples collected in 2018. The assays were calibrated using the manufacturers' instructions; results are in multiples of the assay specific cut-offs (Abbott, Roche, EUROIMMUN) or in arbitrary units (AU/mL, DiaSorin). The assays for IgG and IgT have approximately the same sensitivity and specificity for detecting seroconversion which starts at approximately day 3 after symptom onset, sensitivity reached 93% on day 16 and was 100% for each assay on day 20. The assay for IgA antibodies was superior in sensitivity and had a lower specificity than the others. Bivariate non-parametric correlation coefficients ranged between 0.738 and 0.991. Commercial assays for IgG or total antibodies against SARS-CoV-2 are largely equivalent for establishing seroconversion but differ at high antibody titres. Increased sensitivity to detect seroconversion is afforded by including IgA antibodies. Further international efforts to harmonise assays for antibodies against SARS-CoV-2 are urgently needed.

Keywords: COVID-19; SARS-Cov-2; antibodies; serologic testing.

Copyright © 2021 The Authors. Published by Elsevier Inc. All rights reserved.

Figures

Fig. 1
Fig. 1
Scatterplots of relative concentrations of antibodies against SARS-CoV-2 produced by 5 commercial assays. Top left panel: Roche-IgT versus Abbott-IgG; top right panel: EUROIMMUN-IgG versus Abbott IgG; bottom left panel: EUROIMMUN-IgA versus Abbott-IgG; bottom right panel D: DiaSorin-IgG versus Abbott-IgG. The colours of the data points indicate the time of blood sampling after the onset of clinical symptoms of COVID-19. Green: 1 to 5 days; orange: 6 to 10 days; red: 11 to 20 days; blue: 21 to 47 days. The solid line represents a spline with knots at the 5th, 27.5th, 50th, 72.5th and 95th percentiles of the values on the abscissa variable. AU: arbitrary units, multiples of the cut-off (Color version of the figure is available online.)
Fig. 2
Fig. 2
Time course of antibody concentrations. Medians (and interquartile ranges) plotted against the day of blood sampling after day 0 using the same day groups as in Table 5A. First panel: Abbott-IgG; second panel: EUROIMMUN-IgG; third panel: EUROIMMUN-IgA; fourth panel: Roche-IgT; fifth panel: DiaSorin-IgG.
Fig. 3
Fig. 3
Time course of the sensitivities of 5 commercial assays for antibodies for SARS-CoV2. The abscissa shows the day of blood sampling after symptom onset, the ordinate the respective sensitivities (with lower and higher 95% CI bounds in dotted lines) modelled as monotonous cubic spline with nodes at the means of day quartiles (less than 3 days, 3 days through 7 days, 8 days through 13 days, more than 14 days, highlighted by black vertical lines). Panel A: black: Abbott-IgG; red: EUROIMMUN-IgG; green: EUROIMMUN-IgA; blue: Roche-IgT; orange: Diasorin-IgG; Panel B: black: Abbott-IgG; blue: Roche-IgT; orange: Diasorin-IgG; cyan: Euroimmun-IgG and Euroimmun-IgA combined (Euroimmun-IgG/A) (Color version of the figure is available online.)
Fig. 4
Fig. 4
Predictive values of positive tests (PPV, panel A) and predictive values of negative tests (NPV, panel B) of 5 commercial assays for antibodies against SARS-CoV-2 in relation to disease prevalence rates between 0.001 and 0.05. Dark blue: Abbott-IgG; green: Roche IgT; gray: EUROIMMUN-IgG; orange: EUROIMMUN-IgG; light blue: DiaSorin. Note that the lines for Abbott-IgG and Roche-IgT and for Abbott-IgG, Roche-IgT and EUROIMMUN-IgG in panels A and B, respectively, are coinciding (Color version of the figure is available online.)

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Source: PubMed

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