Peter Findeisen

Bio: Peter Findeisen is an academic researcher. The author has contributed to research in topics: Immunoassay & Reference range. The author has an hindex of 3, co-authored 6 publications receiving 18 citations.

Performance evaluation of the Roche Elecsys Anti-SARS-CoV-2 S immunoassay

Abstract: Background The Elecsys® Anti-SARS-CoV-2 S immunoassay (Roche Diagnostics International Ltd, Rotkreuz, Switzerland) has been developed for the in vitro quantitative detection of antibodies to the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) spike (S) protein. We evaluated the performance of this assay using samples from seven sites in Germany, Austria, and Switzerland. Methods Anonymized frozen, residual serum, or plasma samples from blood donation centers or routine diagnostic testing were used for this study. For specificity and sensitivity analyses, presumed negative samples collected before October 2019 and SARS-CoV-2 PCR-confirmed single or sequential samples were tested, respectively. The performance of the Elecsys Anti-SARS-CoV-2 S immunoassay was also compared with other commercial immunoassays. Results The overall specificity (n=7880 pre-pandemic samples) and sensitivity (n=240 PCR-positive samples [≥14 days post-PCR]) for the Elecsys Anti-SARS-CoV-2 S immunoassay were 99.95% (95% confidence interval [CI]: 99.87–99.99) and 97.92% (95% CI: 95.21– 99.32), respectively. Compared with seven other immunoassays, the Elecsys Anti-SARS-CoV-2 S assay had comparable or greater specificity and sensitivity. The Elecsys Anti-SARS-CoV-2 S immunoassay had significantly higher specificity compared with the LIAISON® SARS-CoV-2 S1/S2 IgG, ADVIA Centaur® SARS-CoV-2 Total, ARCHITECT SARS-CoV-2 IgG, iFlash-SARS-CoV-2 IgM, and EUROIMMUN Anti-SARS-CoV-2 IgG and IgA assays, and significantly higher sensitivity (≥14 days post-PCR) compared with the ARCHITECT SARS-CoV-2 IgG, iFlash-SARS-CoV-2 IgG and IgM, and EUROIMMUN Anti-SARS-CoV-2 IgG assays. Conclusion The Elecsys Anti-SARS-CoV-2 S assay demonstrated a robust and favorable performance across samples from multiple European sites, with a very high specificity and sensitivity for the detection of anti-S antibodies.

Multicentre Performance Evaluation of the Elecsys Anti-SARS-CoV-2 Immunoassay as an Aid in Determining Previous Exposure to SARS-CoV-2.

Abstract: We performed a multicentre evaluation of the Elecsys® Anti-SARS-CoV-2 immunoassay (Roche Diagnostics), an assay utilising a recombinant protein representing the nucleocapsid (N) antigen, for the in vitro qualitative detection of antibodies to severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). Specificity was evaluated using serum/plasma samples from blood donors and routine diagnostic specimens collected before September 2019 (i.e., presumed negative for SARS-CoV-2-specific antibodies); sensitivity was evaluated using samples from patients with polymerase chain reaction (PCR)-confirmed SARS-CoV-2 infection. Point estimates and 95% confidence intervals (CIs) were calculated. Method comparison was performed versus commercially available assays. Overall specificity for the Elecsys Anti-SARS-CoV-2 immunoassay (n = 9575) was 99.85% (95% CI 99.75–99.92): blood donors (n = 6714; 99.82%), routine diagnostic specimens (n = 2861; 99.93%), pregnant women (n = 2256; 99.91%), paediatric samples (n = 205; 100.00%). The Elecsys Anti-SARS-CoV-2 immunoassay demonstrated significantly higher specificity versus LIAISON SARS-CoV-2 S1/S2 IgG (99.71% vs. 98.48%), EUROIMMUN Anti-SARS-CoV-2 IgG (100.00% vs. 94.87%), ADVIA Centaur SARS-CoV-2 Total (100.00% vs. 87.32%) and iFlash SARS-CoV-2 IgM (100.00% vs. 99.58%) assays, and comparable specificity to ARCHITECT SARS-CoV-2 IgG (99.75% vs. 99.65%) and iFlash SARS-CoV-2 IgG (100.00% vs. 100.00%) assays. Overall sensitivity for Elecsys Anti-SARS-CoV-2 immunoassay samples drawn at least 14 days post-PCR confirmation (n = 219) was 93.61% (95% CI 89.51–96.46). No statistically significant differences in sensitivity were observed between the Elecsys Anti-SARS-CoV-2 immunoassay versus EUROIMMUN Anti-SARS-CoV-2 IgG (90.32% vs. 95.16%) and ARCHITECT SARS-CoV-2 IgG (84.81% vs. 87.34%) assays. The Elecsys Anti-SARS-CoV-2 immunoassay showed significantly lower sensitivity versus ADVIA Centaur SARS-CoV-2 Total (85.19% vs. 95.06%) and iFlash SARS-CoV-2 IgG (86.25% vs. 93.75%) assays, but significantly higher sensitivity versus the iFlash SARS-CoV-2 IgM assay (86.25% vs. 33.75%). The Elecsys Anti-SARS-CoV-2 immunoassay demonstrated very high specificity and high sensitivity in samples collected at least 14 days post-PCR confirmation of SARS-CoV-2 infection, supporting its use to aid in determination of previous exposure to SARS-CoV-2.

Performance of an automated anti-SARS-CoV-2 immunoassay in prepandemic cohorts

Abstract: Background The Elecsys® Anti-SARS-CoV-2 immunoassay (Roche Diagnostics) was developed to provide an accurate and reliable method for the detection of antibodies to severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). We evaluated the specificity of the Elecsys Anti-SARS-CoV-2 immunoassay in prepandemic sample cohorts across five sites in Germany, Austria and Switzerland. Methods Specificity of the immunoassay was evaluated using anonymised, frozen, residual serum and/or plasma samples from blood donors or routine diagnostic testing. All samples were collected before September 2019 and therefore presumed negative for SARS-CoV-2-specific antibodies. Cohorts included samples from blood donors, pregnant women and paediatric patients. Point estimates and 95% confidence intervals (CIs) were calculated. Results Overall specificities for the Elecsys Anti-SARS-CoV-2 immunoassay in 9575 samples from blood donors (n = 6714) and diagnostic specimens (n = 2861) were 99.82% (95% CI 99.69-99.91) and 99.93% (95% CI 99.75-99.99), respectively. Among 2256 samples from pregnant women, specificity was 99.91% (95% CI 99.68-99.99). Among 205 paediatric samples, specificity was 100% (95% CI 98.22-100). Conclusion The Elecsys Anti-SARS-CoV-2 immunoassay demonstrated a very high specificity across blood donor samples and diagnostic specimens from Germany, Austria and Switzerland. Our findings support the use of the Elecsys Anti-SARS-CoV-2 immunoassay as a potential tool for determination of an immune response following previous exposure to SARS-CoV-2 in the general population, including in blood donors, pregnant women and paediatric populations.

Multicenter Evaluation of a New, Fully Automated Androstenedione Electrochemiluminescence Immunoassay: Precision Analysis, Method Comparison, and Determination of Reference Ranges.

Abstract: BACKGROUND Androstenedione (ASD) levels can aid diagnosis of hyperandrogenism together with other clinical/laboratory findings. We evaluated performance of the new, automated Elecsys® ASD assay vs an ASD isotope dilution-liquid chromatography-tandem mass spectrometry (ID-LC-MS/MS) reference measurement procedure and determined reference ranges. METHODS Repeatability/intermediate precision were assessed using 3 control levels and 5 human serum pools (n = 75 each; Clinical and Laboratory Standards Institute EP05-A3). Method comparisons vs commercially available immunoassays [IMMULITE ASD (Siemens) and LIAISON ASD (DiaSorin)] and an ID-LC-MS/MS measurement procedure method were conducted using 421 serum samples; Passing-Bablok regression and Pearson's correlation coefficients were calculated. Reference ranges and distribution of values associated with polycystic ovary syndrome (PCOS) were determined in five clinical cohorts using samples from several sites/vendors. RESULTS Repeatability/intermediate precision coefficients of variation across all sites were 2.01% to 3.91% and 2.43% to 4.30%, respectively (mean ASD: 7.80-34.7 nmol/L). The Elecsys ASD assay showed poor agreement with IMMULITE ASD (slope = 0.459; r = 0.856; n = 320), fair agreement with LIAISON ASD (slope = 0.625; r = 0.984; n = 327), and very good agreement with ID-LC-MS/MS (slope = 1.040; r = 0.996; n = 332). Reference ranges (2.5th-97.5th percentiles) were: children (≤8 years; n = 140), <0.525 to 1.81 nmol/L; males (≥18 years; n = 138), 0.979 to 5.32 nmol/L; and postmenopausal females (n = 140), 0.654 to 3.74 nmol/L. Reference range (5th-95th percentiles) for females with fertile cycle (≥18 years; n = 84) was 1.71 to 4.58 nmol/L. The distribution of values (2.5th-97.5th percentiles) in females with PCOS (n = 125) was 2.26 to 12.1 nmol/L. CONCLUSIONS Elecsys ASD assay demonstrated excellent precision and very good agreement with ID-LC-MS/MS. Reference ranges were established to support results interpretation in routine practice.

Antibody response to inactivated COVID-19 vaccine (CoronaVac) in immune-mediated diseases: a controlled study among hospital workers and elderly.

Abstract: To assess antibody response to inactivated COVID-19 vaccine in patients with immune-mediated diseases (IMD) among hospital workers and people aged 65 and older. In this cross-sectional study, we studied 82 hospital workers with IMD (mean age: 42.2 ± 10.0 years) and 300 (mean age: 41.7 ± 9.9 years) controls. Among + 65 aged population, we studied 22 (mean age: 71.4 ± 4.5 years) patients and 47 controls (mean age: 70.9 ± 4.8 years). All study subjects had a negative history for COVID-19. Sera were obtained after at least 21 days following the second vaccination. Anti-spike IgG antibody titers were measured quantitatively using a commercially available immunoassay method. Patients with IMD were significantly less likely to have detectable antibodies than healthy controls both among the hospital workers (92.7% vs 99.7%, p < 0.001) and elderly population (77.3% vs 97.9%, p = 0.011). Among patients with IMD, those using immunosuppressive or immune-modulating drugs (64/75, 85.3%) were significantly less likely to have detectable antibodies compared to those off treatment (29/29, 100%) (p = 0.029). Additionally, a negative association between age and the antibody titer categories among patients (r = − 0.352; p < 0.001) and controls (r = − 0.258; p < 0.001) were demonstrated. Among hospital workers, the vast majority of patients with IMD and immunocompetent controls developed a significant humoral response following the administration of the second dose of inactivated COVID-19 vaccine. This was also true for the elderly population, albeit with lower antibody titers. Immunosuppressive use, particularly rituximab significantly reduced antibody titers. Antibody titers were significantly lower among those aged ≥ 60 years both in patient and control populations. Whether these individuals should get a booster dose warrants further studies.

Anti-SARS-CoV-2 Receptor-Binding Domain Total Antibodies Response in Seropositive and Seronegative Healthcare Workers Undergoing COVID-19 mRNA BNT162b2 Vaccination

Abstract: Background: This study monitored total anti-SARS-CoV-2 (severe acute respiratory syndrome coronavirus 2) RBD (receptor-binding domain) antibodies levels in a large population of healthcare workers undergoing mRNA COVID-19 vaccination. Methods. The study population consisted of employees of Pederzoli Hospital of Peschiera del Garda (Verona, Italy), who underwent voluntary vaccination with two doses of COVID-19 mRNA BNT162b2 (Comirnaty; Pfizer Inc). Venous blood was drawn immediately before the first vaccine dose, as well as 21 days (immediately before second vaccine dose) and 50 days afterwards. Humoral response was assessed with Roche Elecsys Anti-SARS-CoV-2 S total antibodies, on Roche Cobas 6000 (Roche Diagnostics). Results: The final study population consisted of 925 subjects (mean age, 44 ± 13 years; 457 women), 206 (22.3%) anti-SARS-CoV-2 baseline seropositive. The increase of total anti-SARS-CoV-2 RBD antibodies levels 21 days after the first vaccine dose was ~3 orders of magnitude higher in seropositive than in seronegative individuals (11782 vs. 42 U/mL; p < 0.001). Total anti-SARS-CoV-2 RBD antibodies levels further increased by over 30-fold after the second vaccine dose in baseline seronegative subjects, while such increase was only ~1.3-fold in baseline seropositive subjects. In multivariate analysis, total anti-SARS-CoV-2 RBD antibodies level was inversely associated with age after both vaccine doses and male sex after the second vaccine dose in baseline seronegative subjects, while baseline antibodies value significantly predicted immune response after both vaccine doses in baseline seropositive recipients. Conclusion: Significant difference exists in post-mRNA COVID-19 vaccine immune response in baseline seronegative and seropositive subjects, which seems dependent on age and sex in seronegative subjects, as well as on baseline anti-SARS-CoV-2 antibodies level in seropositive patients.

Spike-antibody responses following first and second doses of ChAdOx1 and BNT162b2 vaccines by age, gender, and clinical factors - a prospective community cohort study (Virus Watch)

Abstract: Background Vaccination constitutes the best long-term solution against Coronavirus Disease 2019 (COVID-19). Real-world immunogenicity data are sparse, particularly for ChAdOx1 and in populations with chronic conditions; and given the UK’s extended dosing interval, it is also important to understand antibody responses in SARS-CoV-2-naive individuals following a single dose. Methods Adults aged ≥18 years from households enrolled in Virus Watch, a prospective community cohort study in England and Wales, provided capillary blood samples and self-reported vaccination status. Primary outcome variables were quantitative Spike total antibody levels (U/ml) and seropositivity to Spike (≥0.8 U/ml), as per Roche’s Elecsys Anti-SARS-CoV-2 S assay. Samples seropositive for Nucleocapsid, and samples taken prior to vaccination, were excluded. Outcomes were analysed by days since vaccination, vaccine type (BNT162b2 and ChAdOx1), and a range of self-reported demographic and clinical factors. Results 8,837 vaccinated participants (median age 65 years [IQR: 58, 71]), contributed 17,160 samples (10,508 following ChAdOx1, 6,547 following BNT162b2). Seropositivity to Spike was 96.79% (95% CI 96.42, 97.12) from 28 days following a single dose, reaching 99.34% (98.91, 99.60) from 14 days after a second dose. Seropositivity rates, and Spike-antibody levels rose more quickly following the first dose of BNT162b2, however, were equivalent for both vaccines by 4 and 8 weeks, respectively. There was evidence for lower S-antibody levels with increasing age (p=0.0001). In partially vaccinated 65-79 year-olds, lower S-antibody levels were observed in men compared with women (26.50 vs 44.01 U/ml, p Interpretation A single dose of either BNT162b2 or ChAdOx1 leads to high Spike seropositivity rates in SARS-CoV-2-naive individuals. Observed disparities in antibody levels by vaccine type, age, and comorbidities highlight the importance of ongoing non-pharmaceutical preventative measures for partially vaccinated adults, particularly those who are older and more clinically vulnerable; and high antibody levels across all groups following a second dose demonstrate the importance of complete vaccination. However, the relationship between Spike-antibody levels and protection against COVID-19, and thus the clinical significance of observed disparities, is not yet clear.

Clinical Utility of Elecsys Anti-SARS-CoV-2 S Assay in COVID-19 Vaccination: An Exploratory Analysis of the mRNA-1273 Phase 1 Trial

Abstract: Background The ability to quantify an immune response after vaccination against severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is essential. This study assessed the clinical utility of the quantitative Roche Elecsys® Anti-SARS-CoV-2 S assay (ACOV2S) using samples from the 2019-nCoV vaccine (mRNA-1273) phase 1 trial (NCT04283461). Methods Samples from 30 healthy participants, aged 18–55 years, who received two injections with mRNA-1273 at a dose of 25 μg (n=15) or 100 μg (n=15), were collected at Days 1 (first vaccination), 15, 29 (second vaccination), 43 and 57. ACOV2S results (shown in U/mL – equivalent to BAU/mL per the first WHO international standard) were compared with results from ELISAs specific to antibodies against the Spike protein (S-2P) and the receptor binding domain (RBD) as well as neutralization tests including nanoluciferase (nLUC80), live-virus (PRNT80), and a pseudovirus neutralizing antibody assay (PsVNA50). Results RBD-specific antibodies were already detectable by ACOV2S at the first time point of assessment (d15 after first vaccination), with seroconversion before in all but two participants (25 μg dose group); all had seroconverted by Day 29. Across all post-baseline visits, geometric mean concentration of antibody levels was 3.27–7.48-fold higher in the 100 μg compared with the 25 μg dose group. ACOV2S measurements were highly correlated with those from RBD ELISA (Pearson’s r=0.938; p<0.0001) and S-2P ELISA (r=0.918; p<0.0001). For both ELISAs, heterogeneous baseline results and smaller increases in antibody levels following the second vs first vaccination compared with ACOV2S were observed. ACOV2S showed absence of any baseline noise indicating high specificity detecting vaccine-induced antibody response. Moderate–strong correlations were observed between ACOV2S and neutralization tests (nLUC80 r=0.933; PsVNA50, r=0.771; PRNT80, r=0.672; all p ≤ 0.0001). Conclusion The Elecsys Anti-SARS-CoV-2 S assay (ACOV2S) can be regarded as a highly valuable method to assess and quantify the presence of RBD-directed antibodies against SARS-CoV-2 following vaccination and may indicate the presence of neutralizing antibodies. As a fully automated and standardized method, ACOV2S could qualify as the method of choice for consistent quantification of vaccine-induced humoral response.