Abstract
Purpose: To assess the diagnostic performances of five automated anti-SARS-CoV-2 immunoassays, Epitope (N), Diasorin (S1/S2), Euroimmun (S1), Roche N (N), and Roche S (S-RBD), and to provide a testing strategy based on pre-test probability. Methods: We assessed the receiver operating characteristic (ROC) areas under the curve (AUC) values, along with the sensitivity, specificity, positive predictive values (PPVs), and negative predictive values (NPVs), of each assay using a validation sample set of 172 COVID-19 sera and 185 negative controls against a validated S1-immunofluorescence as a reference method. The three assays displaying the highest AUCs were selected for further serodetection of 2033 sera of a large population-based cohort. Results: In the validation analysis (pre-test probability: 48.1%), Roche N, Roche S and Euroimmun showed the highest discriminant accuracy (AUCs: 0.99, 0.98, and 0.98) with PPVs and NPVs above 96% and 94%, respectively. In the population-based cohort (pre-test probability: 6.2%) these three assays displayed AUCs above 0.97 and PPVs and NPVs above 90.5% and 99.4%, respectively. A sequential strategy using an anti-S assay as screening test and an anti-N as confirmatory assays resulted in a 96.7% PPV and 99.5% NPV, respectively. Conclusions: Euroimmun and both Roche assays performed equally well in high pre-test probability settings. At a lower prevalence, sequentially combining anti-S and anti-N assays resulted in the optimal trade-off between diagnostic performances and operational considerations.
Highlights
Determination of the antibody response against SARS-CoV-2 is a common strategy to monitor the prevalence of SARS-CoV-2 exposure populations across the world [1,2,3,4,5,6].In specific contexts, SARS-CoV-2 serologies might be instrumental for acute diagnostic purposes, when the RT-PCR fails to identify SARS-CoV-2, for example in cases of suboptimal specific pre-analytical situations [7,8]
Our analysis showed that the positive predictive values (PPVs) could be maximized to 100% using either Roche S or Roche N as a screening assay followed by Euroimmun as a confirmatory assay while maintaining an negative predictive values (NPVs) above 99%
At the manufacturer cut-offs, Diasorin and Epitope assays displayed suboptimal NPVs for confident rule-out in high pre-test probability situations, as the low end of the 95% CI observed was 77.9%. These results are in line with a recently published study indicating that the Roche N assay encompassed the highest areas under the curve (AUC) among six existing solutions [20,21]
Summary
Determination of the antibody response against SARS-CoV-2 is a common strategy to monitor the prevalence of SARS-CoV-2 exposure populations across the world [1,2,3,4,5,6]. SARS-CoV-2 serologies might be instrumental for acute diagnostic purposes, when the RT-PCR fails to identify SARS-CoV-2, for example in cases of suboptimal specific pre-analytical situations [7,8]. COVID-19 immunoassays have been developed to assess anti-SARS-CoV-2 antibody response, and enzyme-linked immunosorbent assay (ELISA)/ electrochemiluminescent immunoassay (ECLIA) tests constitute the current analytical standard to quantify these antibodies. Several CE IVD-marked, fully automated SARS-CoV-2 serological assays are currently available on the market. There are substantial differences among them, regarding the kind of antibody isotypes detected (IgG, IgA, IgM or total antibodies), and in terms of the antigen(s) detected, varying between full trimeric Spike protein (S), its specific S1 or S2 subdomains, the receptor binding domain (RBD) located on S1, the nucleocapsid (N), or a combination thereof [2,11,12,13]
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