Evaluation of the IgG antibody response to SARS CoV-2 infection and performance of a lateral flow immunoassay: cross-sectional and longitudinal analysis over 11 months

Abstract

Objective: To evaluate the dynamics and longevity of the humoral immune response to SARS-CoV-2 infection and assess the performance of professional use of the UK-RTC AbC-19 Rapid Test lateral flow immunoassay (LFIA) for the target condition of SARS-CoV-2 spike protein IgG antibodies.

Design: Nationwide serological study.

Setting: Northern Ireland, UK, May 2020-February 2021.

Participants: Plasma samples were collected from a diverse cohort of individuals from the general public (n=279), Northern Ireland healthcare workers (n=195), pre-pandemic blood donations and research studies (n=223) and through a convalescent plasma programme (n=183). Plasma donors (n=101) were followed with sequential samples over 11 months post-symptom onset.

Main outcome measures: SARS-CoV-2 antibody levels in plasma samples using Roche Elecsys Anti-SARS-CoV-2 IgG/IgA/IgM, Abbott SARS-CoV-2 IgG and EuroImmun IgG SARS-CoV-2 ELISA immunoassays over time. UK-RTC AbC-19 LFIA sensitivity and specificity, estimated using a three-reference standard system to establish a characterised panel of 330 positive and 488 negative SARS-CoV-2 IgG samples.

Results: We detected persistence of SARS-CoV-2 IgG antibodies for up to 10 months post-infection, across a minimum of two laboratory immunoassays. On the known positive cohort, the UK-RTC AbC-19 LFIA showed a sensitivity of 97.58% (95.28% to 98.95%) and on known negatives, showed specificity of 99.59% (98.53 % to 99.95%).

Conclusions: Through comprehensive analysis of a cohort of pre-pandemic and pandemic individuals, we show detectable levels of IgG antibodies, lasting over 46 weeks when assessed by EuroImmun ELISA, providing insight to antibody levels at later time points post-infection. We show good laboratory validation performance metrics for the AbC-19 rapid test for SARS-CoV-2 spike protein IgG antibody detection in a laboratory-based setting.

Keywords: COVID-19; diagnostic microbiology; molecular diagnostics.

Figure 1

Two-way correlation scatter plots comparing (A) EuroImmun, (B) Abbott and (C) Roche immunoassays. Pearson χ² test was used to assess correlations. The results for each test were log transformed to ensure results follow a normal distribution. Negative agreement shown as blue dots, red dots show positive agreement for the two immunoassays, while black dots show disagreement and grey dots as the EuroImmun borderline results. Vertical lines mark the Abbott test range 0.25–1.4. n=880. The graphs show positive correlations between all immunoassays evaluated, with the fewest disagreement of results between the log of Roche and the log of EuroImmun. Fit lines locally estimated scatterplot smoothing (LOESS), with 95% CI shaded.

Figure 2

SARS-CoV-2 antibody levels by (A) EuroImmun, (B) Roche and (C) Abbott, relative to weeks since first reported symptoms or positive PCR result (where data available, n=685). RT-PCR-positive individuals are denoted by red dots, while individuals with time since symptom data are denoted in black. Dashed lines delineate log_e equivalent of positivity threshold (EuroImmun 1.1, Roche 1.0, Abbott 1.4) for each test, and the negativity threshold for EuroImmun (0.8; borderline result between the two lines). Black bars indicate median, within IQR boxes for EuroImmun/Roche/Abbott value. Red triangles indicate outliers, based on 1.5×IQR. RT-PCR, reverse transcription-PCR.

Figure 3

AbC-19 extended cohort (n=818) correlation to (A) EuroImmun, (B) Roche and (C) Abbott scores. Box plots overlaid on scatter plot, comparing AbC-19 TT3 test scores with EuroImmun, Roche and Abbott quantitative antibody values. Red linear line of best fit with 95% CI shaded in grey. Black bars indicate median, within IQR boxes for EuroImmun/Roche/Abbott value. Red triangles indicate outliers, based on 1.5×IQR. TT3, Technical Transfer 3.