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

Abstract

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 available in April 2020 in Switzerland.

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 viruses.

Results: In the preliminary phase, among eight IgG/pan-Ig ELISA or CLIA/ECLIA tests, five 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 test showed particular cross-reaction. We observed an important heterogeneity in the development of the antibody response.

Conclusions: The majority of the evaluated tests exhibited high performances of IgG/pan-Ig sensitivity and specificity to detect the serological response of moderately to critically ill hospitalized patients. The IgM and IgA tests showed mostly insufficient performances with no added value for the early diagnostic on the cohort tested in this study.

Keywords: Evaluation; Kits; SARS-CoV-2; Serology.

Fig. 1

Preliminary evaluation: Sensitivity at 0-5, 6-10, 11-15 and above 15 days post-symptoms. Specificity is indicated below each graph. Poor specificities are in red characters.

Fig. 2

Preliminary evaluation. Comparison of the sensitivity and specificity. The sensitivity is given for the sample above 15 days post symptoms.

Fig. 3

Complete evaluation: Sensitivity at 0-5, 6-10, 11-15 and above 15 days post-symptoms. Specificity is indicated below each graph.

Fig. 4

Complete evaluation: Comparison of the sensitivity and specificity. The sensitivity is given for the sample above 15 days post symptoms.

Fig. 5

Kinetic of antibody production per patient. False negative results above 15 days post-symptoms are indicated with red dots and borderline results with orange dots. Patients with several collected sera are represented by connecting lines. Blue lines represent patients that became positive for anti-SARS-CoV-2 IgG more than 15 days post-symptoms.