Comparison of SARS-CoV-2 serological tests with different antigen targets

Abstract

<jats:p>Background These last months, dozens of SARS-CoV-2 serological tests have become available with varying performances. A major effort was completed to compare 17 serological tests. Methods In a preliminary phase, we compared 17 IgG, IgM, IgA and pan Ig serological tests including ELISA, LFA, CLIA and ECLIA on a panel of 182 sera, comprising 113 sera from hospitalized patients with a positive RT-PCR, and 69 sampled before 1st November 2019, expected to give a positive and negative results, respectively. In a second phase, the five best performing and most available tests were further evaluated on a total of 582 sera (178 and 404 expected positive and negative, respectively), allowing the assessment of 20 possible cross-reactions with other virus. Results In the preliminary phase, among eight IgG/pan-Ig ELISA or CLIA/ECLIA tests, four had a sensitivity and specificity above 90% and 98% respectively, and on six IgM/IgA tests, only one was acceptable. Only one LFA test on three showed good performances for both IgG and IgM. For all the tests IgM and IgG aroused concomitantly. In the second phase, no tests showed particular cross-reaction. We observed an important heterogeneity in the development of the antibody response, and that anti-nucleocapside (anti-N) antibodies appeared earlier than the anti-spike (anti-S) proteins. Conclusions The identified SARS-CoV-2 serology tests may be used for the diagnostic of CoviD-19 for negative RT-PCR patients presenting severe to mild suggestive symptoms or particular clinical presentation. Detection of both anti-N and anti-S could be complementary to increase the sensitivity of the analysis.</jats:p>

Temporal Course of SARS-CoV-2 Antibody Positivity in Patients with COVID-19 following the First Clinical Presentation

“…Furthermore, the SARS-CoV-2 IgM test should be used with caution to assess an immune response to COVID-19 that has already been apparent for longer than 21 days. This result is consistent with the findings of Coste et al, who, because of the simultaneous occurrence with IgG, judged IgM to be of no value in diagnosing acute or subacute SARS-CoV-2 infections [ 21 ]. Our study clearly illustrates that an orthogonal testing approach adds valuable diagnostic information.…”

Temporal course of SARS-CoV-2 antibody positivity in patients with COVID-19 following the first clinical presentation

“…IgM test should be used with caution to assess an immune response to COVID-19 that has already been apparent for longer than 21 days. This result is consistent with the findings of Costa et al, who, because of the simultaneous occurrence with IgG, judged IgM to be of no value in diagnosing acute or subacute SARS-CoV-2 infections21 . Our study clearly illustrates that an orthogonal testing approach adds valuable diagnostic information.…”

Performance evaluation of five ELISA kits for detecting anti-SARS-COV-2 IgG antibodies

“…Most developed serology assays target either the spike (S) or the nucleocapsid (N) protein of SARS-CoV-2. Previous studies performed on other HCoV suggested that the anti-nucleocapsid (anti-N) antibody response may appear earlier than the anti-spike (anti-S) response and may wane more rapidly ( Coste et al, 2020 , Chia et al, 2020 ). Here, we expect that the differences in sensitivity between ELISA kits depend on the targeted protein used in each assay.…”

“…However, the sensitivity increased in the kit that solely targets the S1 protein (Lionex). Therefore, a possible explanation for this is that the level of anti-N and anti-S antibodies may be similar during the acute phase of COVID-19 illness, but anti-N antibodies could be waning after the second week ( Coste et al, 2020 , Chia et al, 2020 ). Moreover, this could also explain the high specificity of Lionex compared to the other assays ( Figure 1 ).…”