Performance of six SARS-CoV-2 immunoassays in comparison with microneutralisation

Abstract

There is an urgent need for reliable high-throughput serological assays for the management of the ongoing COVID-19 pandemic. Preferably, the performance of serological tests for a novel virus should be determined with clinical specimens against a gold standard, i.e. virus neutralisation. We compared the performance of six commercial immunoassays for the detection of SARS-COV-2 IgG, IgA and IgM antibodies, including four automated assays [Abbott SARS-COV-2 IgG (CE marked), Diasorin Liaison® SARS-COV-2 S1/S2 IgG (research use only, RUO), and Euroimmun SARS-COV-2 IgG and IgA (CE marked)], and two rapid lateral flow (immunocromatographic) tests [Acro Biotech 2019-nCoV IgG/IgM (CE marked) and Xiamen Biotime Biotechnology SARS-COV-2 IgG/IgM (CE marked)] with a microneutralisation test (MNT). Two specimen panels from serum samples sent to Helsinki University Hospital Laboratory (HUSLAB) were compiled: the patient panel (N=70) included sera from PCR confirmed COVID-19 patients, and the negative panel (N=81) included sera sent for screening of autoimmune diseases and respiratory virus antibodies in 2018 and 2019. The MNT was carried out for all COVID-19 samples (70 serum samples, 62 individuals) and for 53 samples from the negative panel. Forty-one out of 62 COVID-19 patients showed neutralising antibodies.The specificity and sensitivity values of the commercial tests against MNT, respectively, were as follows: 95.1 %/80.5 % (Abbott Architect SARS-CoV-2 IgG), 94.9 %/43.8 % (Diasorin Liaison SARS-CoV-2 IgG; RUO), 68.3 %/87.8 % (Euroimmun SARS-CoV-2 IgA), 86.6 %/70.7 % (Euroimmun SARS-CoV-2 IgG), 74.4 %/56.1 % (Acro 2019-nCoV IgG), 69.5 %/46.3 % (Acro 2019-nCoV IgM), 97.5 %/71.9 % (Xiamen Biotime SARS-CoV-2 IgG), and 88.8 %/81.3 % (Xiamen Biotime SARS-CoV-2 IgM). This study shows variable performance values. Laboratories should carefully consider their testing process, such as a two-tier approach, in order to optimize the overall performance of SARS- CoV-2 serodiagnostics.

Keywords: COVID-19; IgA; IgG; Neutralisation; SARS-CoV-2; Serology.

Fig. 1

Comparison of microneutralisation test (MNT) and immunoassay results, and onset of illness. A) Abbott SARS-CoV-2 IgG assay (index); n = 70. B) Euroimmun SARS-CoV-2 IgA (ratio), n = 70. C) Euroimmun SARS-CoV-2 IgG (ratio), n = 70, D) Liaison SARS-CoV-2 IgG (RUO) (AU/mL), n = 62. E) Microneutralisation titers for 63 serum samples collected from 55 COVID-19 patients, organized according to the time lapse between the onset of symptoms and the sample collection. The geometric mean is marked for each titer with a solid line and immunoassay cut-off values are indicated with a dotted line.

Fig. 2

Test results from the automated immunoassays plotted against each other. A) Euroimmun IgG vs Abbott IgG, B) Euroimmun IgG vs. Euroimmun IgA, C) Euroimmun IgG vs. Liaison IgG (RUO), D) Abbott IgG vs Liaison IgG (RUO), E) Abbott IgG vs Euroimmun IgA, F) Liaison IgG (RUO) vs Euroimmun IgA. The immunoassay cut-off values (dotted line) and trendlines are provided.