Diagnostic and analytical performance evaluation of ten commercial assays for detecting SARS-CoV-2 humoral immune response.

Abstract Objective Analytical validation of newly released SARS-CoV-2 antibody assays in the clinical laboratory is crucial to ensure sufficient performance in respect to its intended use. We aimed to assess analytical and diagnostic performance of 8 (semi-)quantitative assays detecting anti-nucleocapsid IgG (Euroimmun, Id-Vet) or total Ig (Roche), anti-spike protein IgG (Euroimmun, Theradiag, DiaSorin, Thermo Fisher) or both (Theradiag) and 2 rapid lateral flow assays (LFA) (AAZ-LMB and Theradiag). Methods Specificity was evaluated using a cross-reactivity panel of 85 pre-pandemic serum samples. Sensitivity was determined at both the manufacturer's and a 95% specificity cut-off level, using 81 serum samples of patients with a positive rRT-PCR. Sensitivity was determined in function of time post symptoms onset. Results Specificity for all assays ranged from 92.9% to 100% (Roche and Thermo Fisher) with the exception of the Theradiag IgM LFA (82.4%). Sensitivity in asymptomatic patients ranged between 41.7% and 58.3%. Sensitivity on samples taken  20 days since symptom onset (80%–96% and 92.9%–100%, respectively). From 20 days after symptom onset, the Roche, Id-vet and Thermo Fisher assays all met the sensitivity (>95%) and specificity (>97%) targets determined by the WHO. Antibody signal response was significantly higher in the critically ill patient group. Conclusion Antibody detection can complement rRT-PCR for the diagnosis of COVID-19, especially in the later stage, or in asymptomatic patients for epidemiological purposes. Addition of IgM in LFAs did not improve sensitivity.