Performance of Elecsys® HCV Duo Immunoassay for Diagnosis and Assessment of Treatment Response in HCV Patients with or without HIV Infection.

BACKGROUND/OBJECTIVES: The Elecsys® HCV Duo immunoassay (Roche Diagnostics International Ltd., Rotkreuz, Switzerland) detects both antibodies to hepatitis C virus (anti-HCV) and HCV core antigen (HCV-Ag) and has shown excellent diagnostic performance in blood donor samples. We aim to validate its use for diagnosing chronic HCV infection and assessing sustained virological response (SVR) post-direct-acting antivirals (DAAs) in patients with or without HIV infection. METHODS: Blood samples from 100 healthy controls, as well as 64 HCV mono-infection and 136 HCV-HIV coinfections, were collected before and 12-24 weeks after DAAs. The assay performance for determining active infection at baseline and SVR was compared with HCV RNA. RESULTS: Overall, 156 (78.0%) of HCV-infected patients had HCV genotype 1, and the SVR rate was 96.5%. The sensitivity, specificity, and area under the ROC curve (AUROC) for HCV diagnosis at baseline were 99.50% (95% confidence interval [CI], 96.82-99.97%), 100% (95%CI, 95.39-100%), and 0.998 (95%CI, 0.992-1.003), respectively. The corresponding results for HCV-Ag in determining SVR were 57.14% (95%CI, 20.24-88.19%), 97.41% (95%CI, 93.73-99.04%), and 0.773 (95%CI, 0.543-1.003), respectively. The assay also exhibited comparable sensitivity and specificity between HCV mono- and coinfection. CONCLUSIONS: Our study showed that the Elecsys® HCV Duo immunoassay effectively diagnosed HCV infection, regardless of HIV status, making it suitable for managing high-risk populations in resource-limited settings.

A Dried Blood Spot protocol for high-throughput quantitative analysis of SARS-CoV-2 RBD serology based on the Roche Elecsys system.

SARS-CoV-2 spreads pandemically since 2020; in 2021, effective vaccinations became available and vaccination campaigns commenced. Still, it is hard to track the spread of the infection or to assess vaccination success in the broader population. Measuring specific anti-SARS-CoV-2 antibodies is the most effective tool to track the spread of the infection or successful vaccinations. The need for venous-blood sampling however poses a significant barrier for large studies. Dried-blood-spots on filter-cards (DBS) have been used for SARS-CoV-2 serology in our laboratory, but so far not to follow quantitative SARS-CoV-2 anti-spike reactivity in a longitudinal cohort. We developed a semi-automated protocol or quantitative SARS-CoV-2 anti-spike serology from self-sampled DBS, validating it in a cohort of matched DBS and venous-blood samples (n = 825). We investigated chromatographic effects, reproducibility, and carry-over effects and calculated a positivity threshold as well as a conversion formula to determine the quantitative binding units in the DBS with confidence intervals. Sensitivity and specificity reached 96.63% and 97.81%, respectively, compared to the same test performed in paired venous samples. Between a signal of 0.018 and 250 U/mL, we calculated a correction formula. Measuring longitudinal samples during vaccinations, we demonstrated relative changes in titers over time in several individuals and in a longitudinal cohort over four follow-ups. DBS sampling has proven itself for anti-nucleocapsid serosurveys in our laboratory. Similarly, anti-spike high-throughput DBS serology is feasible as a complementary assay. Quantitative measurements are accurate enough to follow titer dynamics in populations also after vaccination campaigns. This work was supported by the Bavarian State Ministry of Science and the Arts; LMU University Hospital, LMU Munich; Helmholtz Center Munich; University of Bonn; University of Bielefeld; German Ministry for Education and Research (proj. nr.: 01KI20271 and others) and the Medical Biodefense Research Program of the Bundeswehr Medical Service. Roche Diagnostics provided kits and machines for analyses at discounted rates. The project is funded also by the European-wide Consortium ORCHESTRA. The ORCHESTRA project has received funding from the European Union's Horizon 2020 research and innovation program under grant agreement No 101016167. The views expressed in this publication are the sole responsibility of the author, and the Commission is not responsible for any use that may be made of the information it contains.IMPORTANCESARS-CoV-2 has been spreading globally as a pandemic since 2020. To determine the prevalence of SARS-CoV-2 antibodies among populations, the most effective public health tool is measuring specific anti-SARS-CoV-2 antibodies induced by infection or vaccination. However, conducting large-scale studies that involve venous-blood sampling is challenging due to the associated feasibility and cost issues. A more cost-efficient and less invasive method for SARS-CoV-2 serological testing is using Dried-Blood-Spots on filter cards (DBS). In this paper, we have developed a semi-automated protocol for quantifying SARS-CoV-2 anti-spike antibodies from self-collected DBS. Our laboratory has previously successfully used DBS sampling for anti-nucleocapsid antibody surveys. Likewise, conducting high-throughput DBS serology for anti-spike antibodies is feasible as an additional test that can be performed using the same sample preparation as the anti-nucleocapsid analysis. The quantitative measurements obtained are accurate enough to track the dynamics of antibody levels in populations, even after vaccination campaigns.

Alzheimer's disease biomarker utilization at first referral enhances differential diagnostic precision with simultaneous exclusion of Creutzfeldt-Jakob disease.

Most suspected Creutzfeldt-Jakob disease (CJD) cases are eventually diagnosed with other disorders. We assessed the utility of investigating Alzheimer's disease (AD) biomarkers and neurofilament light (NfL) in patients when CJD is suspected. The study cohort consisted of cerebrospinal fluid (CSF) samples referred for CJD biomarker screening wherein amyloid beta 1-42 (Aß1-42), phosphorylated tau 181 (p-tau181), and total tau (t-tau) could be assessed via Elecsys immunoassays (n = 419) and NfL via enzyme-linked immunosorbent assay (ELISA; n = 161). In the non-CJD sub cohort (n = 371), 59% (219/371) had A+T- (abnormal Aß1-42 only) and 21% (79/371) returned A+T+ (abnormal Aß1-42 and p-tau181). In the 48 CJD subjects, a similar AD biomarker profile distribution was observed. To partially address the prevalence of likely pre-symptomatic AD, NfL was utilized to assess for neuronal damage. NfL was abnormal in 76% (25/33) of A+T- subjects 40 to 69 years of age, 80% (20/25) of whom had normal t-tau. This study reinforces AD as an important differential diagnosis of suspected CJD, highlighting that incorporating AD biomarkers and NfL at initial testing is worthwhile.

Interference against a newly labeled substance with ruthenium sulfonate complexes showing discrepant thyroid function test results.

We report here two patients exhibiting a combination of falsely elevated serum levels of free thyroxine (FT4), free triiodothyronine (FT3), and thyrotropin receptor antibodies (TRAb), measured using Elecsys assay kits (Roche Diagnostics GmbH). The first patient was a 74-year-old man misdiagnosed with Graves' disease and treated with methimazole. The second patient was a 48-year-old woman whose serum FT4 and FT3 concentrations were found to be high during a blood test. These patients denied taking biotin or any other supplements. Further detailed examination, including a heterophilic blocking tube test, revealed the presence of serum antibodies. The abnormal reactions were observed only using the improved assay kits using ruthenium (Ru) sulfonate instead of Ru as a chemiluminescent agent. Therefore, serum antibodies to the Ru sulfonate complex caused the pseudo-high levels of FT4, FT3, and TRAb. To our knowledge, this is the first report showing that antibodies to the Ru sulfonate complex in the electrochemiluminescence immunoassay can cause falsely elevated levels of the combination, leading to discrepant thyroid function test results. We emphasize that in cases of abnormal test results, alternative assay methods should be considered for further examination; unusual test results should not be impulsively interpreted, even when using revised assay kits.

A fast and sensitive high-throughput assay to assess polysorbate-degrading hydrolytic activity in biopharmaceuticals.

Hydrolysis of polysorbate in biopharmaceutical products has been ascribed to the enzymatic activity from trace levels of residual host cell proteins. In recent years, significant efforts to identify the causative enzymes typically used elaborate, material-intensive and time-consuming approaches. Therefore, the lack of fast and sensitive assays to monitor their activity remains a major bottleneck for supporting process optimization and troubleshooting activities where time and sample throughput are crucial constraints. To address this bottleneck, we developed a novel Electrochemiluminescence-based Polysorbase Activity (EPA) assay to measure hydrolytic activities in biotherapeutics throughout the drug substance manufacturing process. By combining the favorable features of an in-house designed surrogate substrate with a well-established detection platform, the method yields fast (∼36 h turnaround time) and highly sensitive readouts compatible with high-throughput testing. The assay capability for detecting substrate conversion in a precise and reliable manner was demonstrated by extensive qualification studies and by employing a number of recombinant hydrolases associated with polysorbate hydrolysis. In addition, high assay sensitivity and wide applicability were confirmed for in-process pool samples of three different antibody products by performing a head-to-head comparison between this method and an established liquid chromatography - mass spectrometry based assay for the quantification of free fatty acids. Overall, our results suggest that this new approach is well-suited to resolve differences in hydrolytic activity through all stages of purification.

Accuracy Validation of the Elecsys HBsAg II Quant Assay and Its Utility in Resolving Equivocal Qualitative HBsAg Results.

Background and Objectives: There are reports of false qualitative HBsAg results, because of various causes, such as samples with low HBsAg concentrations that may produce false positives. The main aims of this study were to validate the analytical accuracy and to assess the utility of the Elecsys assay compared to that of the qualitative HbsAg assay as a screening test in resolving equivocal qualitative HbsAg results. Materials and Methods: The limit of blank (LoB), the limit of detection (LoD), the limit of quantification (LoQ), and linearity were estimated to validate the analytical accuracy of the Elecsys HBsAg II Quant assay. A total of 449 serum samples showing initial equivocal results (1-50 index) were evaluated by Elecsys HBsAg II Quant and ADVIA Centaur HBsAg II assays. Results: The LoQ of the assay was determined to be 0.050 IU/mL, as provided by the manufacturer. The Kappa agreement between the two assays was almost perfect, at 0.9669, despite seven discordant results. With a specificity of 100% at new cut-off index value ≥5.42, about 78 samples (17%, 78/449) with index value ≥5.42 were interpreted as positives without further duplicate tests, however the remaining 371 samples with index value <5.42 need to be confirmed with additional HBV marker assays. Conclusions: We confirm that the Elecsys HBsAg II Quant assay is accurate and sensitive for HBV infection and recommend it as an alternative confirmatory HBsAg assay for resolving equivocal qualitative HBsAg results.

Diagnostic performance of CSF biomarkers in a well-characterized Australian cohort of sporadic Creutzfeldt-Jakob disease.

The most frequently utilized biomarkers to support a pre-mortem clinical diagnosis of sporadic Creutzfeldt-Jakob disease (sCJD) include concentrations of the 14-3-3 and total tau (T-tau) proteins, as well as the application of protein amplification techniques, such as the real time quaking-induced conversion (RT-QuIC) assay, in cerebrospinal fluid (CSF). Utilizing CSF from a cohort of neuropathologically confirmed (definite) sCJD (n = 50) and non-CJD controls (n = 48), we established the optimal cutpoints for the fully automated Roche Elecsys® immunoassay for T-tau and the CircuLexTM 14-3-3 Gamma ELISA and compared these to T-tau protein measured using a commercially available assay (INNOTEST hTAU Ag) and 14-3-3 protein detection by western immunoblot (WB). These CSF specimens were also assessed for presence of misfolded prion protein using the RT-QuIC assay. T-tau showed similar diagnostic performance irrespective of the assay utilized, with ~90% sensitivity and specificity. The 14-3-3 protein detection by western blot (WB) has 87.5% sensitivity and 66.7% specificity. The 14-3-3 ELISA demonstrated 81.3% sensitivity and 84.4% specificity. RT-QuIC was the single best performing assay, with a sensitivity of 92.7% and 100% specificity. Our study indicates that a combination of all three CSF biomarkers increases sensitivity and offers the best chance of case detection pre-mortem. Only a single sCJD case in our cohort was negative across the three biomarkers, emphasizing the value of autopsy brain examination on all suspected CJD cases to ensure maximal case ascertainment.

Robustness of CSF Aß42/40 and Aß42/P-tau181 measured using fully automated immunoassays to detect AD-related outcomes.

INTRODUCTION: This study investigated the comparability of cerebrospinal fluid (CSF) cutoffs for Elecsys immunoassays for amyloid beta (Aß)42/Aß40 or Aß42/phosphorylated tau (p-tau)181 and the effects of measurement variability when predicting Alzheimer's disease (AD)-related outcomes (i.e., Aß-positron emission tomography [PET] visual read and AD neuropathology). METHODS: We studied 750 participants (BioFINDER study, Alzheimer's Disease Neuroimaging Initiative [ADNI], and University of California San Francisco [UCSF]). Youden's index was used to identify cutoffs and to calculate accuracy (Aß-PET visual read as outcome). Using longitudinal variability in Aß-negative controls, we identified a gray zone around cut-points where the risk of an inconsistent predicted outcome was >5%. RESULTS: For Aß42/Aß40, cutoffs across cohorts were <0.059 (BioFINDER), <0.057 (ADNI), and <0.058 (UCSF). For Aß42/p-tau181, cutoffs were <41.90 (BioFINDER), <39.20 (ADNI), and <46.02 (UCSF). Accuracy was ≈90% for both Aß42/Aß40 and Aß42/p-tau181 using these cutoffs. Using Aß-PET as an outcome, 8.7% of participants fell within a gray zone interval for Aß42/Aß40, compared to 4.5% for Aß42/p-tau181. Similar findings were observed using a measure of overall AD neuropathologic change (7.7% vs. 3.3%). In a subset with CSF and plasma Aß42/40, the number of individuals within the gray zone was ≈1.5 to 3 times greater when using plasma Aß42/40. DISCUSSION: CSF Aß42/p-tau181 was more robust to the effects of measurement variability, suggesting that it may be the preferred Elecsys-based measure in clinical practice and trials.

Utility of Roche Elecsys anti-SARS-CoV-2 S in ascertaining post-vaccine neutralizing antibodies.

With widespread global COVID-19 vaccine coverage, a scalable, cost-effective, and standardized tool to ascertain post-vaccine immunity is a dire need. Neither clinical evaluations of vaccine efficacy, nor live virus antibody neutralization assays fulfill these criteria. Commercially available anti-S binding immunological assays have the potential to fill this gap, but need to be systematically evaluated for their utility to serve as surrogates for the aforementioned, widely accepted tools of determining vaccine efficacy. In this study, we evaluated an anti-S binding immunological assay (Roche Elecsys Anti-SARS-CoV-2 S) by utilizing two hundred and fifty-five archived serum specimens, either pre-pandemic, or those exposed to natural infections or vaccines with their neutralizing titers pre-determined through a live virus, pseudotyped antibody neutralization assay. Roche Elecsys Anti-SARS-CoV-2 S demonstrated good sensitivity (98%) and specificity (99%), just as has been reported in some other previously conducted studies using this assay. Only a mild correlation, however, with the live virus pseudotyped lentivirus antibody neutralization assay (Spearman's r = 0.26) was observed. We conclude that, as such, Elecsys Anti-SARS-CoV-2 S has a high sensitivity and specificity for detecting anti-SARS-CoV-2 S proteins, though the assay does not always correlate well with live virus assays for quantitative outcomes.

An accurate fully automated panel of plasma biomarkers for Alzheimer's disease.

INTRODUCTION: There is a great need for fully automated plasma assays that can measure amyloid beta (Aß) pathology and predict future Alzheimer's disease (AD) dementia. METHODS: Two cohorts (n = 920) were examined: Panel A+ (n = 32 cognitively unimpaired [CU], n = 106 mild cognitive impairment [MCI], and n = 89 AD) and BioFINDER-1 (n = 461 CU, n = 232 MCI). Plasma Aß42/Aß40, phosphorylated tau (p-tau)181, two p-tau217 variants, ApoE4 protein, neurofilament light, and GFAP were measured using Elecsys prototype immunoassays. RESULTS: The best biomarker for discriminating Aß-positive versus Aß-negative participants was Aß42/Aß40 (are under the curve [AUC] 0.83-0.87). Combining Aß42/Aß40, p-tau181, and ApoE4 improved the AUCs significantly (0.90 to 0.93; P< 0.01). Adding additional biomarkers had marginal effects (ΔAUC ≤0.01). In BioFINDER, p-tau181, p-tau217, and ApoE4 predicted AD dementia within 6 years in CU (AUC 0.88) and p-tau181, p-tau217, and Aß42/Aß40 in MCI (AUC 0.87). DISCUSSION: The high accuracies for Aß pathology and future AD dementia using fully automated instruments are promising for implementing plasma biomarkers in clinical trials and clinical routine.

Dietary Consumption With Vitamin D Status Among Pregnant Women: A Descriptive-Analytic Study.

AIM: This study aimed to investigate the relationship between vitamin D status and diet between pregnant and non-pregnant women who attended a Maternity Teaching Hospital (MTH) in Sulaymaniyah, Iraq. MATERIALS AND METHODS: A descriptive-analytic (cross-sectional) study was conducted at the MTH in Sulaymaniyah, Iraq. Data was collected from January to October 2022, including demographics, obstetric information, and dietary data. Vitamin D levels were measured using the Roche Elecsys assay (Roche Diagnostics, Indianapolis, Indiana, United States). The non-pregnant group consisted of women who were not pregnant at the time of this study, and the pregnant group had women with second trimester pregnancy at the time of enrollment. RESULT: The study revealed a significant prevalence of vitamin D deficiency among pregnant women. In the study, pregnant participants (56.0% aged 30-39) and non-pregnant participants (54.3% aged 20-29) had similar ages (p>0.05). Both groups mostly had overweight individuals, with pregnant participants having a slightly higher mean body mass index (BMI). While vitamin D deficiency was more prevalent among pregnant women, the differences were not statistically significant. Notably, higher dairy intake was positively associated with higher vitamin D levels. Urban residency was common in both groups. Dietary habits were mostly similar, except for tea consumption (p<0.05), with non-tea drinkers having higher vitamin D levels. However, dietary patterns did not strongly correlate with vitamin D levels in the non-pregnant group. CONCLUSION: This study reveals a significant prevalence of vitamin D deficiency among pregnant women, although the differences between pregnant and non-pregnant groups were not statistically significant. The positive association between higher dairy intake and increased vitamin D levels underscores the potential impact of dietary choices on vitamin D status during pregnancy. However, the study also suggests that dietary patterns alone may not strongly correlate with vitamin D levels in non-pregnant women. Overall, this highlights the importance of addressing vitamin D deficiency in pregnant women and underscores the need for personalized dietary guidance, taking into account individual preferences and habits to promote better maternal health.

Long-Term Antibody Response against SARS-CoV-2 in Health Care Workers: Effectiveness of Homologous and Heterologous Regimens and Their Relation to Systemic Vaccine-Associated Symptoms.

This prospective study provides data on the long-term humoral immunogenicity of a heterologous off-label vaccine regimen combining the adenoviral-vectored ChAdOx1 nCoV-19 from Astra-Zeneca (ChAd) with the mRNA-1273 vaccine from Moderna (m1273) in comparison with two different homologous mRNA vaccine schedules. Of the 316 COVID-19 naïve adult health care workers (HCW) included to complete a survey on vaccine-associated symptoms (VAS), 197 had received the homologous BNT162b2 mRNA vaccine from Pfizer/BioNTech (BNT/BNT), 76 the homologous m1273/m1273, and 43 the heterologous ChAd/m1273 vaccine regimen. The concentration of antibodies against SARS-CoV-2 spike protein in plasma 5−7 months after the second vaccine dose was higher in the m1273/m1273 and ChAd/m1273 than the BNT/BNT vaccine group. The frequency of systemic VAS after the first vaccine dose was 86% after ChAd compared with 35% and 39% after BNT and m1273, respectively (p < 0.0001), and after the second vaccine dose, the highest (89%) in the m1273/m1273 group (p < 0.001). Individuals with systemic VAS achieved higher levels of antibodies irrespective of vaccine regimen. In conclusion, VAS serve as a strong predictor of long-term humoral immune response, and the heterologous ChAd/m1273 vaccine regimen provides an at least equal long-term humoral immune response compared with the standard vaccine regimens used in Denmark.

Cortisol values during the standard-dose cosyntropin stimulation test: Personal experience with Elecsys cortisol II assay.

Purpose: There has been debate regarding the appropriate cortisol cutoff during the cosyntropin stimulation test (CST) when newer cortisol assays are used. We aimed to evaluate the proper cortisol values during the standard dose CST in patients with normal hypothalamic-pituitary-adrenal (HPA) axis when the Elecsys® Cortisol II assay from Roche Diagnostics is used. Methods: We retrospectively reviewed the medical records of patients evaluated for possible adrenal insufficiency using the standard-dose (250 mcg) CST from January 2018 to December 2020 and eventually judged to have a normal HPA axis. All the CSTs were done in the outpatient setting. Evaluation by an endocrinologist, restrictive exclusion criteria including prior glucocorticoid and opioid use, and lack of glucocorticoid treatment for at least 6 months after the CST was used to define normal HPA axis. The results are reported in the median (range). Results: We identified 63 patients who met the inclusion criteria and were considered to have a normal HPA axis. The median age was 54.7 (27.6-89.1) years; 32 (51%) were female, and 27 (43%) were white. The duration of follow-up after the CST without any glucocorticoid replacement was 13.9 (6.3-43.9) months. Cortisol levels were 21.7 (15.7-29.1) µg/dl and 24.4 (17.9-35.8) µg/dl at 30- and 60-minutes after cosyntropin administration, respectively. The lowest cortisol levels at 30 and 60 minutes for patients with either normal TSH or gonadal axis (n=47) or in whom both axes were normal (n=18) were similar to the ones of the entire cohort. Conclusion: Our study supports using a lower than previously recommended cortisol cutoff value at 30 minutes after Cosyntropin using the Roche Elecsys® Cortisol II assay. The lowest cortisol levels in our cohort were 15.7 and 17.9 µg/dL at 30 and 60 minutes after the CST, respectively. Therefore, it is essential to consider the time of cortisol draw after cosyntropin administration.

Kinetics of anti-SARS-CoV-2 antibody titer in healthy adults up to 6 months after BNT162b2 vaccination measured by two immunoassays: A prospective cohort study in Japan.

BACKGROUND: Although several assays are used to measure anti-receptor-binding domain (RBD) antibodies induced after severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) vaccination, the assays are not fully comparable in practice. This study evaluated the immunogenicity of the BNT162b2 mRNA vaccine in healthy adults using two immunoassays. METHODS: This prospective cohort study included SARS-CoV-2-naïve adults, predominantly healthcare workers, aged 20-64 years, who received two BNT162b2 vaccine doses between March and May 2021. Blood samples were collected before the first vaccination (S0), before the second vaccination (S1), 4 weeks after the second vaccination (S2), and 6 months after the second vaccination (S3). anti-RBD antibodies were measured using the Architect SARS-CoV-2 IgG II Quant (Abbott Laboratory) and Elecsys anti-SARS-CoV-2 S (Roche Diagnostics) assays. RESULTS: Among the 385 participants, the geometric mean antibody titers (GMTs) on the Architect assay (AU/mL) were 7.5, 693, 7007, and 1030 for S0, S1, S2, and S3, respectively. The corresponding GMTs on the Elecsys assay (U/mL) were 0.40, 24, 928, and 659, respectively. The GMT ratio (S3/S2) was 0.15 on the Architect and 0.71 on the Elecsys assay. The correlation between antibody titers measured with the two assays were strong at all time points after vaccination (Spearman's correlation coefficient: 0.74 to 0.86, P < 0.01 for all). GMT was significantly lower in the older age group after vaccination (P < 0.01), with no significant differences according to sex. Seroprotection (≥5458 AU/mL on the Architect assay and ≥ 753 U/mL on the Elecsys) at each time point was 0 %, 1 %, 67 %, and 1 % on the Architect assay and 0 %, 1 %, 62 %, and 43 % on the Elecsys, respectively. CONCLUSIONS: Two BNT162b2 vaccine doses resulted in adequate anti-RBD antibody response, which varied by age. As the two assays showed different kinetics, the results of single immunoassays should be interpreted with caution.

Comparison between a new assay system, Elecsys® Anti-p53, and conventional MESACUP™ for the detection of serum anti-p53 antibodies: A multi-institutional study.

The sensitivity and specificity of a new automated electrochemiluminescence immunoassay system, Elecsys® Anti-p53 (Elecsys), were compared with that of the conventional serum anti-p53 antibody (s-p53-Ab) enzyme-linked immunosorbent assay kit [MESACUP anti-p53 test (MESACUP)]. Elecsys and MESACUP were used to analyze the levels of s-p53-Abs in patients with esophageal, colorectal and breast cancer. A total of 532 controls and 288, 235 and 329 patients with esophageal, colorectal and breast cancer, respectively, were enrolled. Additionally, the sera of patients with benign diseases of the esophagus, colorectal system and breast, patients with autoimmune diseases and healthy volunteers were analyzed as controls. Sensitivity and specificity were compared between the two assay systems. Positive agreement rates were 58.7% in all samples, 71.2% in esophageal samples, 73.6% in colorectal samples and 35.1% in breast samples. Negative agreement rates for the different cancer types were ≥97.1% and the overall agreement rates were ≥92.3%. When the specificities of the two assays were aligned for all samples, Elecsys demonstrated higher sensitivities for all types of analyzed cancer together, as well as for esophageal, colorectal and breast cancer, respectively. Although positive concordance between the two assay systems was low in terms of specificity, Elecsys had a higher sensitivity than the MESACUP.

Bias in IGF-1 concentrations and interpretation across three different clinical laboratory assays.

In this study, we compared the DiaSorin LiaisonXL IGF-1 immunoassay to both the Roche Elecsys IGF-1 immunoassay and to the liquid chromatography-high resolution mass spectrometry (LC-MS) IGF-1 assay. Our study shows a constant positive bias in DiaSorin compared to the Roche immunoassay (mean 42 µg/L, 24%), and a proportional positive bias in DiaSorin compared to the LC-MS method (mean 49 µg/L, 29%). Further, we demonstrate the potential clinical impact of this bias by evaluating 43 adult samples, collected over a 2-month period, which were shown to be discrepant based on a chart review. Despite the positive analytical bias in the Diasorin assay compared to the LC-MS assay, the Diasorin assay upper reference limits were lower than those of the LC-MS assay. This effect caused nine out of forty-three samples to show falsely elevated results when they were clinically diagnosed as negative for acromegaly. Discussed in the context of previous literature, our findings emphasize the importance of adjusting reference intervals for IGF-1 assays based on the clinical needs of a patient population.

Seroprevalence of SARS-CoV-2 infection among frontline police personnel in Mumbai, India.

Introduction: A serosurvey was designed to ascertain the extent of infection among police personnel in Mumbai, India, during the last week of January 2021, at the end of the first wave of the COVID-19 pandemic, and just before the introduction of vaccination. Methods: The survey was carried out to screen for SARS-CoV-2 among 3232 police personnel. Of the 3176 participants willing for blood sample collection, 3077 personnel were found to be eligible for testing antibodies against the SARS-CoV-2 virus using the Roche Diagnostics' Elecsys Anti-SARS-CoV-2 assay. Results: The overall seroprevalence was 74.1% (95% CI 72.5-75.6). Males (75.1%, 73.4-76.8) had significantly higher seroprevalence than females (69.8%, 66.0-73.3), 18-39 years age group (76.4%, 74.4-78.3) than 40-59 years age group (70.6%, 67.9-73.1), non-officers (75.2%, 73.5-76.7) than officers (63.8%, 58.2-69.0), and personnel without comorbidities (75.0%, 73.3-76.6) than with comorbidities (69.7%, 65.6-73.5). Additionally, personnel with resident members positive for COVID-19 (89.6%, 84.7-93.1), personnel having reported COVID-19 earlier (95.5%, 93.8-96.7), and personnel having PCR positivity earlier (96.4%, 94.7-97.6) had significantly higher seroprevalences than others. All other variables, including diabetes and blood glucose status, lipid levels and thyroid enzymes, were not significantly associated with the seroprevalence levels. Conclusions: Almost three-fourths of frontline police personnel had evidence of past COVID-19 infection at the end of the first wave in January 2021, just before the introduction of COVID-19 vaccination. These frontline non-healthcare essential workers are an important risk group, and amenable to rapid serosurveys. These findings may help in estimating transmission status in the general community, along with disease burden, aiding prioritization of healthcare services.

Comparison of ACCEL ELISA COVID-19 with Elecsys Anti-SARS-CoV-2 for Screening of COVID-19.

OBJECTIVE: Although real-time reverse transcription-PCR (RT-PCR) is the gold standard for diagnosing coronavirus disease 2019 (COVID-19), simpler and faster antibody detection tests can be complementary for diagnosis of COVID-19. To manage the COVID-19 pandemic, the need for serologic testing has increased. In this report, the newly developed antibody detection assays ACCEL ELISA COVID-19 (ACCEL) and Elecsys anti-SARS-CoV-2 (Elecsys) were evaluated. METHODS: Serum samples submitted for routine laboratory testing were analyzed (66 and 161 PCR-positive and PCR-negative samples). After the samples were aliquoted, antibody detection tests were performed using ACCEL and Elecsys assays. RESULTS: When detection of viral RNA using RT-PCR was set as the reference method for diagnosis of COVID-19, the sensitivity was 83.3% and 75.8, and the specificity was 96.9 and 99.4% in ACCEL and Elecsys, respectively. The true positivity rates of ACCEL and Elecsys assays were 57.1%/42.9%, 57.1%/28.6%, 77.8%/66.7%, and 97.1%/97.1% among the specimens collected ≤3, 4-7, 8-14, and >14 days after symptom onset, respectively. CONCLUSIONS: The ACCEL assay showed high sensitivity in samples collected within 7 days after symptom onset. Because many patients are asymptomatic in the early stage of SARS-CoV-2 infection, the ACCEL assay could be a good screening tool due to high sensitivity in the early stage of SARS-CoV-2 infection.

Comparing SARS-CoV-2 Antibody Responses after Various COVID-19 Vaccinations in Healthcare Workers.

Coronavirus disease 2019 (COVID-19) vaccination began for healthcare workers in South Korea at the end of February 2021. This study investigated severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) antibody responses after various COVID-19 vaccinations in healthcare workers. Blood specimens of 497 vaccinated healthcare workers were collected. Inoculated vaccines were ChAdOx1 (AstraZeneca/Oxford), BNT162b2 (Pfizer/BioNTech), JNJ-78436735 (Janssen), and mRNA-1273 (Moderna). Each specimen was tested for antibodies against SARS-CoV-2 using Elecsys Anti-SARS-CoV-2 S assay (Roche Diagnostics), SARS-CoV-2 IgG II Quant assay (Abbott), and R-FIND SARS-CoV-2 Neutralizing Antibody kit (SG medical Inc.). A questionnaire was used to investigate adverse events related to vaccination. We found that 99.5% of the subjects showed a 96-100% positive rate in all three antibody assays, regardless of the vaccine type. The antibody-positive rate of completed vaccination groups reached 96-100%, and antibody quantities significantly increased 2 weeks after vaccination. The antibody values measured approximately 3 months after BNT162b2 inoculation significantly correlated with adverse events.