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

• Published in: Journal of immunological methods 2021-06, Vol.493, p.113043-113043, Article 113043
• Main Authors: Mylemans, Marnix, Van Honacker, Eveline, Nevejan, Louis, Van Den Bremt, Stefanie, Hofman, Laura, Poels, Jeroen, Cattoir, Lien, Boel, An, Van Hoovels, Lieve
• Format: Article
• Language: English
• Subjects: Adolescent; Adult; Aged; Aged, 80 and over; Antibodies, Viral - blood; Antibody; Biomarkers - blood; COVID-19; COVID-19 - blood; COVID-19 - diagnosis; COVID-19 - immunology; COVID-19 - virology; COVID-19 Serological Testing; Female; Host-Pathogen Interactions; Humans; Humoral response; Immunity, Humoral; Immunoglobulin G - blood; Male; Middle Aged; Predictive Value of Tests; Reagent Kits, Diagnostic; Reproducibility of Results; Retrospective Studies; SARS-CoV-2; SARS-CoV-2 - immunology; Serology; Young Adult
• ISSN: 0022-1759; 1872-7905; 1872-7905
• DOI: 10.1016/j.jim.2021.113043

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). 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. 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. 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. •Evaluation diagnostic performance of ten commercial SARS-CoV-2 serological assays.•Antibody detection can complement real-time reverse transcriptase-PCR for diagnosis of COVID-19.•Sensitivity depends on time of sampling; >90% in samples taken >20 days post symptom onset.•Antibody signal response was significantly higher in the critically ill patient group.•Addition of IgM in the lateral flow immunoassays did not improve sensitivity compared to IgG alone.