Validation of a commercially available SARS-CoV-2 serological immunoassay.

Meyer, Benjamin; Torriani, Giulia; Yerly, Sabine; Mazza, Lena; Calame, Adrien; Arm-Vernez, Isabelle; Zimmer, Gert; Agoritsas, Thomas; Stirnemann, Jérôme; Spechbach, Hervé; Guessous, Idris; Stringhini, Silvia; Pugin, Jérôme; Roux-Lombard, Pascale; Fontao, Lionel; Siegrist, Claire-Anne; Eckerle, Isabella; Vuilleumier, Nicolas; Kaiser, Laurent (2020). Validation of a commercially available SARS-CoV-2 serological immunoassay. Clinical microbiology and infection, 26(10), pp. 1386-1394. Elsevier 10.1016/j.cmi.2020.06.024

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OBJECTIVES

To validate the diagnostic accuracy of a Euroimmun SARS-CoV-2 IgG and IgA immunoassay for COVID-19.

METHODS

In this unmatched (1:2) case-control validation study, we used sera of 181 laboratory-confirmed SARS-CoV-2 cases and 326 controls collected before SARS-CoV-2 emergence. Diagnostic accuracy of the immunoassay was assessed against a whole spike protein-based recombinant immunofluorescence assay (rIFA) by receiver operating characteristic (ROC) analyses. Discrepant cases between ELISA and rIFA were further tested by pseudo-neutralization assay.

RESULTS

COVID-19 patients were more likely to be male and older than controls, and 50.3% were hospitalized. ROC curve analyses indicated that IgG and IgA had high diagnostic accuracies with AUCs of 0.990 (95% Confidence Interval [95%CI]: 0.983-0.996) and 0.978 (95%CI: 0.967-0.989), respectively. IgG assays outperformed IgA assays (p=0.01). Taking an assessed 15% inter-assay imprecision into account, an optimized IgG ratio cut-off > 2.5 displayed a 100% specificity (95%CI: 99-100) and a 100% positive predictive value (95%CI: 96-100). A 0.8 cut-off displayed a 94% sensitivity (95%CI: 88-97) and a 97% negative predictive value (95%CI: 95-99). Substituting the upper threshold for the manufacturer's, improved assay performance, leaving 8.9% of IgG ratios indeterminate between 0.8-2.5.

CONCLUSIONS

The Euroimmun assay displays a nearly optimal diagnostic accuracy using IgG against SARS-CoV-2 in patient samples, with no obvious gains from IgA serology. The optimized cut-offs are fit for rule-in and rule-out purposes, allowing determination of whether individuals in our study population have been exposed to SARS-CoV-2 or not. IgG serology should however not be considered as a surrogate of protection at this stage.

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