Comparison of four commercial, automated antigen tests to detect SARS-CoV-2 variants of concern

• Published in: Medical microbiology and immunology Vol. 210; no. 5-6; pp. 263 - 275
• Main Authors: Osterman, Andreas, Iglhaut, Maximilian, Lehner, Andreas, Späth, Patricia, Stern, Marcel, Autenrieth, Hanna, Muenchhoff, Maximilian, Graf, Alexander, Krebs, Stefan, Blum, Helmut, Baiker, Armin, Grzimek-Koschewa, Natascha, Protzer, Ulrike, Kaderali, Lars, Baldauf, Hanna-Mari, Keppler, Oliver T.
• Format: Journal Article
• Language: English
• Published: Berlin/Heidelberg Springer Berlin Heidelberg 01.12.2021; Springer Nature B.V
• Subjects: Amino acids; Antigens; Antigens, Viral - analysis; Antigens, Viral - immunology; Automation; Automation - economics; Automation - methods; Biomedical and Life Sciences; Biomedicine; Clinical isolates; Cohort Studies; Coronaviruses; COVID-19 - diagnosis; COVID-19 - virology; COVID-19 Serological Testing - economics; COVID-19 Serological Testing - methods; Enzyme-linked immunosorbent assay; False Negative Reactions; Germany; Humans; Immunology; Laboratories; Medical Microbiology; Nucleocapsids; Original Investigation; Pandemics; Patients; SARS-CoV-2 - genetics; SARS-CoV-2 - immunology; SARS-CoV-2 - isolation & purification; Sensitivity and Specificity; Severe acute respiratory syndrome coronavirus 2; Virology; Germany; Diagnostic test; Sensitivity; Specificity; VOC; Nucleocapsid protein; Automated SARS-CoV-2 antigen test
• ISSN: 0300-8584; 1432-1831
• DOI: 10.1007/s00430-021-00719-0

A versatile portfolio of diagnostic tests is essential for the containment of the severe acute respiratory syndrome coronavirus type 2 (SARS-CoV-2) pandemic. Besides nucleic acid-based test systems and point-of-care (POCT) antigen (Ag) tests, quantitative, laboratory-based nucleocapsid Ag tests for SARS-CoV-2 have recently been launched. Here, we evaluated four commercial Ag tests on automated platforms and one POCT to detect SARS-CoV-2. We evaluated PCR-positive ( n  = 107) and PCR-negative ( n  = 303) respiratory swabs from asymptomatic and symptomatic patients at the end of the second pandemic wave in Germany (February–March 2021) as well as clinical isolates EU1 (B.1.117), variant of concern (VOC) Alpha (B.1.1.7) or Beta (B.1.351), which had been expanded in a biosafety level 3 laboratory. The specificities of automated SARS-CoV-2 Ag tests ranged between 97.0 and 99.7% (Lumipulse G SARS-CoV-2 Ag (Fujirebio): 97.03%, Elecsys SARS-CoV-2 Ag (Roche Diagnostics): 97.69%; LIAISON ® SARS-CoV-2 Ag (Diasorin) and SARS-CoV-2 Ag ELISA (Euroimmun): 99.67%). In this study cohort of hospitalized patients, the clinical sensitivities of tests were low, ranging from 17.76 to 52.34%, and analytical sensitivities ranged from 420,000 to 25,000,000 Geq/ml. In comparison, the detection limit of the Roche Rapid Ag Test (RAT) was 9,300,000 Geq/ml, detecting 23.58% of respiratory samples. Receiver-operating-characteristics (ROCs) and Youden’s index analyses were performed to further characterize the assays’ overall performance and determine optimal assay cutoffs for sensitivity and specificity. VOCs carrying up to four amino acid mutations in nucleocapsid were detected by all five assays with characteristics comparable to non-VOCs. In summary, automated, quantitative SARS-CoV-2 Ag tests show variable performance and are not necessarily superior to a standard POCT. The efficacy of any alternative testing strategies to complement nucleic acid-based assays must be carefully evaluated by independent laboratories prior to widespread implementation.