Clinical performance of four immunoassays for antibodies to SARS-CoV-2, including a prospective analysis for the diagnosis of COVID-19 in a real-life routine care setting

Abstract

Objectives: The aim of the present study was to evaluate the clinical performance of four SARS-CoV-2 immunoassays and their contribution in routine care for the diagnosis of COVID-19, in order to benefit of robust data before their extensive use.

Methods: The clinical performance of Euroimmun ELISA SARS-CoV-2 IgG, Abbott SARS-CoV-2 IgG, Wantai SARS-CoV-2 Ab ELISA, and DiaPro COVID-19 IgG confirmation were evaluated in the context of both a retrospective and a prospective analysis of COVID-19 patients. The retrospective analysis included plasma samples from 63 COVID-19 patients and 89 control (pre-pandemic) patients. The prospective study included 203 patients who tested either negative (n = 181) or positive (n = 22) by RT-PCR before serology sampling.

Results: The specificity was 92.1 %, 98.9 %, 100 % and 98.9 % and the sensitivity 14 days after onset of symptoms was 95.6 %, 95.6 %, 97.8 % and 95.6 % for Euroimmun IgG, Abbott IgG, Wantai Ab, and DiaPro IgG confirmation SARS-CoV-2 immunoassays, respectively. The low specificity of Euroimmun IgG (for ratio <5) was not confirmed in routine care setting (98.5 % negative agreement). Serology was complementary to RT-PCR in routine care and lead to identification of false positive (Ct>38, <2 targets detected) and false negative RT-PCR results (>1 month post onset of symptoms).

Conclusions: Serology was complementary to RT-PCR for the diagnosis of COVID-19 at least 14 days after onset of symptoms. First line serology testing can be performed with Wantai Ab or Abbott IgG assays, while DiaPro IgG confirmation assay can be used as an efficient confirmation assay.

Keywords: Antibody; CLIA; COVID-19; ELISA; Immunoassay; RT-PCR; SARS-CoV-2; Serology.

Fig. 1

Clinical performance of SARS-CoV-2 immunoassays. A) Comparison of SARS-CoV-2 immunoassays results between COVID-19 patients and control patients. Black arrow indicates the heart transplant patient who tested negative with all immunoassays more than 14 days after onset of symptoms. B) ROC curves for evaluation of performances of SARS-CoV-2 immunoassays for samples ≥14 days post onset of symptoms.

Fig. 2

Agreement between RT-PCR and serology for 203 patients. COVID-19 confirmed if positive RT-PCR (>1 gene) and/or Ab detected with two or more immunoassays.

Fig. 3

Delay between serology and first RT-PCR or onset of symptoms. Delay between serology and first RT-PCR (plain dots) or onset of symptoms (empty dots). The dashed line represents early serology testing before 14 days after onset of symptoms.