Evaluation of three fully-automated SARS-CoV-2 antibody assays

Abstract

ObjectivesSerological assays for detection of SARS-CoV-2 antibodies are increasingly used during the COVID-19 pandemic caused by the SARS-Coronavirus-2. Here we evaluated the analytical and clinical performance of three commercially available SARS-CoV-2 antibody assays.MethodsA total of 186 samples from 58 patients with PCR-confirmed COVID-19 infection were measured using SARS-CoV-2 antibody assays by Siemens Healthineers, Roche Diagnostics and Euroimmun. Additionally, 123 control samples, including samples collected before December 2019 and samples with potential cross-reactive antibodies were analyzed. Diagnostic specificity, sensitivity, agreement between assays and ROC curve-derived optimized thresholds were determined. Furthermore, intra- and inter-assay precision and the potential impact of interfering substances were investigated.ResultsSARS-CoV-2 antibody assays by Siemens and Roche showed 100% specificity. The Euroimmun assay had 98 and 100% specificity, when borderline results are considered as positive or negative, respectively. Diagnostic sensitivity for samples collected ≥14 days after PCR-positivity was 97.0, 89.4 and 95.5% using the Siemens, Roche and Euroimmun assay, respectively. Sensitivity of the Roche assay can be increased using an optimized cut-off index (0.095). However, a simultaneous decrease in specificity (98.4%) was observed. Siemens showed 95.8 and 95.5% overall agreement with results of Euroimmun and Roche assay, respectively. Euroimmun and Roche assay exhibited 92.6% overall agreement. Discordant results were observed in three COVID-19 patients and in one COVID-19 patient none of the investigated assays detected antibodies.ConclusionsThe investigated assays were highly specific and sensitive in detecting SARS-CoV-2 antibodies in samples obtained ≥14 days after PCR-confirmed infection. Discordant results need to be investigated in further studies.

Differences in Performance Characteristics Among Four High-Throughput Assays for the Detection of Antibodies Against SARS-CoV-2 Using a Common Set of Patient Samples

“…The specificities would remain high even if the two presumed false-negative RT-PCR patient samples were included in the analysis. There has been little literature regarding the Siemens assay, although recent reports indicate excellent specificity, 13 , 20-22 which our findings further support with a wide array of samples. The specificities of the DiaSorin and EUROIMMUN assays are similar to, or modestly lower, than other evaluations, 2-4 , 8 -11,13-17,19,21,36 although some of the studies reporting better performance had very small number of samples or nonchallenging cross-reactivity panels.…”

Multicenter Evaluation of the Clinical Performance and the Neutralizing Antibody Activity Prediction Properties of 10 High-Throughput Serological Assays Used in Clinical Laboratories

“…For instance, we obtained 85% and 83% sensitivities for the Roche and Abbott assays in the ≥15 days period while the companies claimed 100% sensitivity at the same time frame. Similarly to our findings, other studies reported smaller Se values varying from 73 to 89% and 82 to 92% for the Roche and Abbott assays respectively (19)(20)(21). Clinical performance characteristic variations between serological studies are not unusual and are highly dependant on the patient cohort used for evaluation.…”

“…Regarding the rapid antibody detection devices, we obtained relatively good Se and Sp values which were lower than those claimed by the manufacturers but similar to published studies (19,26). Downloaded from so far that could be bypassed by several proposed strategies.…”

Structures of the SARS ‐CoV‐2 nucleocapsid and their perspectives for drug design

“…In addition, as the N protein could interact with many host proteins during the infection process and cause a robust humoral immune response after infection, the divergent charge distribution surfaces could be critical to identify specific interacting cellular proteins and develop specific immune‐based rapid diagnostic test (Burbelo et al , ; Ni et al , ). Besides the serological assays for detection of SARS‐CoV‐2 antibodies (Hörber et al , ), the rapid detection of viral antigens based on specific antibodies can provide essential information for disease monitoring (Che et al , ). Therefore, to develop high‐affinity and specific anti‐N antibodies would be critical to enhance the rapid molecular diagnosis for COVID‐19.…”