An evaluation of COVID-19 serological assays informs future diagnostics and exposure assessment

Abstract

The world is entering a new era of the COVID-19 pandemic in which there is an increasing call for reliable antibody testing. To support decision making on the deployment of serology for either population screening or diagnostics, we present a detailed comparison of serological COVID-19 assays. We show that among the selected assays there is a wide diversity in assay performance in different scenarios and when correlated to virus neutralizing antibodies. The Wantai ELISA detecting total immunoglobulins against the receptor binding domain of SARS CoV-2, has the best overall characteristics to detect functional antibodies in different stages and severity of disease, including the potential to set a cut-off indicating the presence of protective antibodies. The large variety of available serological assays requires proper assay validation before deciding on deployment of assays for specific applications.

Fig. 1. Performance of commercial assays for the detection of SARS-CoV-2-specific antibodies.

Correlation of SARS-CoV-2 neutralizing antibody titers tested by a plaque reduction neutralization assay (PRNT50) to antibodies measured by selected assays. (a) Wantai Ig total ELISA, (b) Wantai IgM ELISA, (c) Euroimmun IgG ELISA, (d) Euroimmun IgA ELISA, (e)  DiaSorin Liaison XL IgG chemiluminescence immunoassay, (f) Cellex IgM/IgG, (g) InTec IgM/IgG, (h) Orient gene/Healgen IgM/IgG. Turquoise dots indicate patient specimen collected ≤7 days post onset of  symptoms  (dps), magenta  dots indicate samples collected from 8–14 dps, gray dots indicate specimen collected more than 14 dps. Dotted lines indicate the cut-off for positivity of each assay, as indicated by the manufacturer: Wantai ELISAs, OD ratio > 1; Euroimmun ELISAs, OD ratio > 1.1; DiaSorin Liaison IgG >15 AU/ml. OD: optical density, AU: arbitrary units, r: correlation coefficient. (i) Percentages of specificities and sensitivities of the various platforms tested. The arrow bar indicates the upper and lower limit of the 95% CI. Source data are provided as a Source Data file.