Evaluation of four commercial, fully automated SARS-CoV-2 antibody tests suggests a revision of the Siemens SARS-CoV-2 IgG assay

Abstract

Objectives: Serological tests detect antibodies against Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2) in the ongoing coronavirus disease-19 (COVID-19) pandemic. Independent external clinical validation of performance characteristics is of paramount importance. Methods: Four fully automated assays, Roche Elecsys Anti-SARS-CoV-2, Abbott SARS-CoV-2 IgG, Siemens SARS-CoV-2 total (COV2T) and SARS-CoV-2 IgG (COV2G) were evaluated using 350 pre-pandemic samples and 700 samples from 245 COVID-19 patients (158 hospitalized, 87 outpatients). Results: All tests showed very high diagnostic specificity. Sensitivities in samples collected at least 14 days after disease onset were slightly lower than manufacturers' claims for Roche (93.04%), Abbott (90.83%), and Siemens COV2T (90.26%), and distinctly lower for Siemens COV2G (78.76%). Concordantly negative results were enriched for immunocompromised patients. ROC curve analyses suggest a lowering of the cut-off index for the Siemens COV2G assay. Finally, the combination of two anti-SARS-CoV-2 antibody assays is feasible when considering borderline reactive results. Conclusions: Thorough on-site evaluation of commercially available serologic tests for detection of antibodies against SARS-CoV-2 remains imperative for laboratories. The potentially impaired sensitivity of the Siemens COV2G necessitates a switch to the company's newly filed SARS-CoV-2 IgG assay (sCOVG) for follow-up studies. A combination of tests could be considered in clinical practice.

Clinical validation of the quantitative Siemens SARS-CoV-2 spike IgG assay (sCOVG) reveals improved sensitivity and a good correlation with virus neutralization titers

“…In contrast, the new Siemens sCOVG was significantly more sensitive (90.5%). This is well in line with the sensitivities observed for all other assays evaluated with our cohort (range 90.4% to 93%) [19]. Additionally, the sensitivity is essentially in line with the manufacturer’s claims, which state a sensitivity of 91.14% for samples between day 14-20 after PCR-diagnosis and 96.41% for samples dated ≥ 21 days after PCR diagnosis (Supplemental Table S1).…”

“…193 patients with reverse transcription polymerase chain reaction (RT-PCR)-confirmed SARS-CoV-2 infection dating between March and August, 2020, were screened for this study. All samples have been previously tested with the Siemens SARS-CoV-2 IgG assay (COV2G) [19]. 15 patients (7.8%) were excluded, as no sample material was available for analysis.…”

“…Blood samples were prepared as described previously [19]. We evaluated the Siemens SARS-CoV-2 IgG assay (sCOVG) on the Siemens ADVIA Centaur XP platform (Siemens, Munich, Germany).…”

“…Recently, we reported a clinical evaluation of the Siemens SARS-CoV-2 IgG (COV2G) in comparison to three other fully automated SARS-CoV-2 chemiluminescence immunoassays on high throughput random access analysers (Roche Elecsys Anti-SARS-CoV-2, Abbott SARS-CoV-2 IgG, Siemens SARS-CoV-2 total). In that study, the sensitivity of the Siemens COV2G test (78.8%) was unexpectedly low and inferior to that of the other assays (range 90.8% to 93%) [19]. In the meantime, Siemens has launched a new SARS-CoV-2 IgG test (sCOVG) by November 18, 2020.…”

A comprehensive antigen production and characterization study for easy-to-implement, highly specific and quantitative SARS-CoV-2 antibody assays

“…The underlying sample collections were reviewed and approved by the ethics committee of the Medical University of Vienna (EK 595/2005, EK 404/2011, EK 518/2011), or by the ethics committee of the City of Vienna (EK-11-117-0711), respectively. Samples from hospitalized COVID-19 patients at the University Hospital of Innsbruck, reconvalescent COVID-19 patients with persistent cardio-pulmonary damage participating in a prospective observational study (CovILD-study, ClinicalTrials.gov number, NCT04416100, Reference: PMID: 33303539) and reconvalescent persons volunteering as plasma donors were used for test validation in Innsbruck ( 66 ). The underlying sample collections were reviewed and approved by the ethics committee of the Medical University of Innsbruck (EK 1103/2020, EK 1167/2020).…”