Side-by-Side Comparison of Three Fully Automated SARS-CoV-2 Antibody Assays with a Focus on Specificity.

In the context of the COVID-19 pandemic, numerous new serological test systems for the detection of anti-SARS-CoV-2 antibodies rapidly have become available. However, the clinical performance of many of these is still insufficiently described. Therefore, we compared 3 commercial CE-marked, SARS-CoV-2 antibody assays side by side. We included a total of 1154 specimens from pre-COVID-19 times and 65 samples from COVID-19 patients (≥14 days after symptom onset) to evaluate the test performance of SARS-CoV-2 serological assays by Abbott, Roche, and DiaSorin. All 3 assays presented with high specificities: 99.2% (98.6-99.7) for Abbott, 99.7% (99.2-100.0) for Roche, and 98.3% (97.3-98.9) for DiaSorin. In contrast to the manufacturers' specifications, sensitivities only ranged from 83.1% to 89.2%. Although the 3 methods were in good agreement (Cohen's Kappa 0.71-0.87), McNemar tests revealed significant differences between results obtained from Roche and DiaSorin. However, at low seroprevalences, the minor differences in specificity resulted in profound discrepancies of positive predictive values at 1% seroprevalence: 52.3% (36.2-67.9), 77.6% (52.8-91.5), and 32.6% (23.6-43.1) for Abbott, Roche, and DiaSorin, respectively. We found diagnostically relevant differences in specificities for the anti-SARS-CoV-2 antibody assays by Abbott, Roche, and DiaSorin that have a significant impact on the positive predictive values of these tests.

Perkmann T ，Perkmann-Nagele N ，Breyer MK ，Breyer-Kohansal R ，Burghuber OC ，Hartl S ，Aletaha D ，Sieghart D ，Quehenberger P ，Marculescu R ，Mucher P ，Strassl R ，Wagner OF ，Binder CJ ，Haslacher H ... -  《-》

Head-to-Head Comparison of Two SARS-CoV-2 Serology Assays.

While molecular techniques remain the gold standard for diagnosis of acute SARS-CoV-2 infection, serological tests have the unique potential to ascertain how much of the population has been exposed to the COVID-19 pathogen. There have been limited published studies to date documenting the performance of SARS-CoV-2 antibody assays. We compared the DiaSorin Liaison SARS-CoV-2 S1/S2 IgG and Roche Diagnostics Elecsys Anti-SARS-CoV-2 assays using 228 samples spanning patients with positive PCR for SARS-CoV-2, patients with compatible symptoms but negative PCR, pre-COVID specimens, and potential cross-reactives. Both assays detected antibodies in 18/19 samples collected at least one week after a positive PCR result. Neither method consistently detected antibodies in specimens collected within one week of a positive PCR result (sensitivity < 50%), but antibodies were detected by only Roche in four samples in this time frame. Using 139 pre-COVID and 35 PCR-negative samples, the Roche and DiaSorin assays demonstrated specificities of 100.0% and 98.9%, respectively. Neither assay demonstrated cross-reactivity from other coronaviruses (229E, HKU1, NL63, OC43), respiratory pathogens (adenovirus, metapneumovirus, rhinovirus/enterovirus), or antibodies to other viruses (HIV, EBV, CMV, HBV, HCV, HAV). Overall, the qualitative interpretations afforded by the Roche and DiaSorin assays agreed for 97% of samples evaluated. Minor discrepancies in sensitivity and specificity were observed between methods, with the differences in specificity more clinically significant for our low-prevalence population. For the DiaSorin assay, all disagreements with the Roche assay occurred in samples with quantitative signals near the cut-off determining positivity.

Merrill AE ，Jackson JB ，Ehlers A ，Voss D ，Krasowski MD ... -  《-》

Clinical evaluation of five different automated SARS-CoV-2 serology assays in a cohort of hospitalized COVID-19 patients.

The global market for SARS-CoV-2-immunoassays is becoming ever more crowded with antibody-tests of various formats, targets and technologies, careful evaluation is crucial for understanding the implications of individual test results. Here, we evaluate the clinical performance of five automated immunoassays on a set of clinical samples. Serum/plasma samples of 75 confirmed COVID-19 patients and 320 pre-pandemic serum samples of healthy blood donors were subjected to two IgG and three total antibody SARS-CoV-2-immunoassays. All test setups were automated workflows. Positivity of assays (onset of symptoms > 10 days) ranged between 68.4 % and 81.6 % (Diasorin 68.4 %, Euroimmun 70.3 %, Siemens 73.7 %, Roche 79.0 % and Wantai 81.6 %). All examined assays demonstrated high specificity of >99 % (Euroimmun, Diasorin: 99.1 %, Wantai: 99.4 %) but only two reached levels above 99.5 % (Roche: 99.7 %, Siemens 100 %). Interestingly, there was no overlap in false positive results between the assays. The strongest correlation of quantitative results was observed between the Diasorin and Euroimmun IgG tests (r2 = 0.76). Overall, we observed no difference in the distribution of test results between female and male patients (p-values: 0.18-0.87). A significant difference between severely versus critically ill patients was demonstrated for the Euroimmun, Diasorin, Wantai and Siemens assays (p-values:0.041). All assays showed good clinical performance. Our data confirm that orthogonal test strategies as recommended by the CDC can enhance clinical specificity. However, the suboptimal rates of test positivity found at time of hospitalization in this cohort underline the importance of molecular diagnostics to rule out/confirm active infection with SARS-CoV-2.

Pflüger LS ，Bannasch JH ，Brehm TT ，Pfefferle S ，Hoffmann A ，Nörz D ，van der Meirschen M ，Kluge S ，Haddad M ，Pischke S ，Hiller J ，Addo MM ，Lohse AW ，Schulze Zur Wiesch J ，Peine S ，Aepfelbacher M ，Lütgehetmann M ... -  《-》

Multi-Platform Comparison of SARS-CoV-2 Serology Assays for the Detection of COVID-19.

COVID-19 is caused by the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), a novel beta-coronavirus that is responsible for the 2019 coronavirus pandemic. Acute infections should be diagnosed by polymerase chain reaction (PCR) based tests, but serology tests can demonstrate previous exposure to the virus. We compared the performance of the Diazyme, Roche, and Abbott SARS-CoV-2 serology assays using 179 negative participants to determine negative percentage agreement (NPA) and in 60 SARS-CoV-2 PCR-confirmed positive patients to determine positive percentage agreement (PPA) at 3 different time frames following a positive SARS-CoV-2 PCR result. At ≥15 days, the PPA (95% CI) was 100 (86.3-100)% for the Diazyme IgM/IgG panel, 96.0 (79.7-99.9)% for the Roche total Ig assay, and 100 (86.3-100)% for the Abbott IgG assay. The NPA (95% CI) was 98.3 (95.2-99.7)% for the Diazyme IgM/IgG panel, 99.4 (96.9-100)% for the Roche total Ig assay, and 98.9 (96.0-99.9)% for the Abbott IgG assay. When the Roche total Ig assay was combined with either the Diazyme IgM/IgG panel or the Abbott IgG assay, the positive predictive value was 100% while the negative predictive value remained greater than 99%. Our data demonstrates that the Diazyme, Roche, and Abbott SARS-CoV-2 serology assays have similar clinical performances. We demonstrated a low false-positive rate across all 3 platforms and observed that false positives observed on the Roche platform are unique compared to those observed on the Diazyme or Abbott assays. Using multiple platforms in tandem increases the PPVs, which is important when screening populations with low disease prevalence.

Suhandynata RT ，Hoffman MA ，Kelner MJ ，McLawhon RW ，Reed SL ，Fitzgerald RL ... -  《-》

Evaluation of SARS-CoV-2 IgG antibody response in PCR positive patients: Comparison of nine tests in relation to clinical data.

Naaber P ，Hunt K ，Pesukova J ，Haljasmägi L ，Rumm P ，Peterson P ，Hololejenko J ，Eero I ，Jõgi P ，Toompere K ，Sepp E ... -  《PLoS One》