Performance assessment of 11 commercial serological tests for SARS-CoV-2 on hospitalised COVID-19 patients

Abstract

Background: Commercial availability of serological tests to evaluate immunoglobulins (Ig) targeting severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) has grown exponentially since the start of the coronavirus disease 2019 (COVID-19) outbreak. Thorough validation of these tests is important before use as epidemiological tools to infer seroprevalence in specific populations and as diagnostic tools to complement molecular approaches (e.g., quantitative reverse transcription-polymerase chain reaction).

Methods: Commercial serological tests from 11 suppliers were assayed side-by-side using 126 samples from SARS-CoV-2-infected inpatients and 36 from healthy and HIV-infected individuals.

Results: The majority of the tests assayed have >95% specificity. For the sensitivity calculation, samples were stratified by days since symptoms onset; sensitivity peaks at 16-21 days for IgM and IgA (maximum 91.2%, Euroimmun) and, dependant on the test, at 16-21 or >21 days for IgG (maximum 94.1%, Snibe). Data from semiquantitative tests show that patients with a severe clinical presentation have lower levels of Ig targeting SARS-CoV-2 at <10 days since symptoms onset and higher levels at >21 days, compared to patients with a non-severe presentation.

Conclusions: This study highlights the heterogeneity of sensitivity and generally high specificity of the serological tests and establishes a basis for their usefulness to complement diagnostic techniques and population seroprevalence studies.

Keywords: COVID-19; Clinical presentation; Qualitative and semiquantitative tests; Sensitivity; Serological tests; Specificity.

Figure 1

Receiver operator characteristic (ROC) curves of the assayed semiquantitative tests. AUC: Area Under the Curve. Ig: Immunoglobulin.

Figure 2

Comparison of the Ig levels in patients with a severe and non-severe clinical presentation using the semiquantitative tests Abbott, Euroimmun and Snibe. Each dot represents one sample and the solid thick lines correspond to the group’s median. Solid thin lines represent each test’s cut-off value. In the case of Euroimmun test, the shadowed grey banner refers to borderline values according to the manufacturer (between 0.8 and 1.1). Since the y-axis has a log scale that does not allow the representation of zero, in those situations (Snibe IgG and IgM) arbitrary values were attributed, and a dashed grey line was represented in this value. For values above the detection limit (Euroimmun IgA), a random value of 20 was attributed and represented as a dashed grey line. Groups median were compared using a Mann–Whitney U-tests; significant differences were represented as: * for P < 0.05; ** for P < 0.01; ***, P < 0.001.