Abbott Architect Research Articles

Performance of 4 Automated SARS-CoV-2 Serology Assay Platforms in a Large Cohort Including Susceptible COVID-19-Negative and COVID-19-Positive Patients.

Background Anti-SARS-CoV-2 serological responses may have a vital role in controlling the spread of the disease. However, the comparative performance of automated serological assays has not been determined in susceptible patients with significant co-morbidities.MethodsIn this study, we used a large number of COVID-19 negative patient samples (n = 2030) as well as COVID-19 positive patient samples (n = 112) to compare the performance of four serological assay platforms; Siemens Healthineers Atellica IM Analyzer, Siemens Healthineers Dimension EXL Systems, Abbott ARCHITECT, and Roche cobas.ResultsAll four serology assay platforms exhibited comparable negative percent agreement with negative COVID-19 status ranging from 99.2-99.7%, and positive percent agreement from 84.8-87.5% with positive real-time reverse transcriptase polymerase chain reaction (RT-PCR) results. Of the 2142 total samples, only 38 samples (1.8%) yielded discordant results on one or more platforms. However, only 1.1% (23/2030) of COVID-19 negative cohort results was discordant whereas discordance was 10-fold higher for the COVID-19 positive cohort at 11.3% (15/112). Of the total 38 discordant results, 34 were discordant on only one platform.ConclusionSerology assay performance was comparable across the four platforms assessed in a large population of COVID-19 negative patients with relevant comorbidities. The pattern of discordance shows that samples were discordant on a single assay platform, and discordance rate was 10-fold higher in the COVID-19 positive population.Impact statementHigh negative percent agreement reinforces the reliability of serology testing especially in a cohort of at-risk patients. Serology platform discordance highlights the importance of a two-test strategy for properly identifying seroconverted patients.

Diagnostic accuracy comparison of three fully automated chemiluminescent immunoassay platforms for the detection of SARS-CoV-2 antibodies

BackgroundSerological test is an essential surveillance tool to track down the extensiveness of SARS-CoV-2 transmission and subsequently to move out from the enforced lockdown stage. ObjectiveThe study measures the diagnostic accuracy of three popular chemiluminescent immunoassay (CLIA) based automated platforms for the detection of anti-SARS-CoV-2 antibodies and compares their agreements. Study designSerum samples of 594 COVID-19 positive patients and 100 samples from pre-COVID cases were tested by three CLIA based automated platforms: Abbott architect i2000SR, Roche cobas e411 and Yhlo iFlash 1800 and their diagnostic accuracy were compared by the area under the curves (AUC) value obtained from receiver operator characteristic (ROC) curves. Cohen’s kappa statistic and McNemar’s test were used to interpret the agreement between the platforms. ResultsAll three platforms showed high specificity as claimed by the manufacturer. Sensitivity was calculated as 64.48 % (58.67–70.3) for Abbott, 80.48 % (76.62–84.34) for Roche and 76.94 % (72.65–81.23) for Yhlo. AUC was maximum for Roche (0.929). The Cohen’s kappa value was determined in between 0.69−0.89 as the inter-rater agreements. ConclusionThe overall statistical analysis demonstrated cobas e411 as the diagnostically most accurate platform among the three.

A high prevalence of potential HIV elite controllers identified over 30 years in Democratic Republic of Congo

BackgroundIn-depth analysis of the HIV pandemic at its epicenter in the Congo basin has been hampered by 40 years of political unrest and lack of functional public health infrastructure. In recent surveillance studies (2017-18), we found that the prevalence of HIV in Kinshasa, Democratic Republic of Congo (11%) far exceeded previous estimates.Methods10,457 participants were screened in Kinshasa with rapid tests from 2017-2019. Individuals confirmed as reactive by the Abbott ARCHITECT HIV Ag/Ab Combo assay (n=1968) were measured by the Abbott RealTime HIV-1 viral load assay. Follow up characterization of samples was performed with alternate manufacturer viral load assays, qPCR for additional blood borne viruses, unbiased next generation sequencing, and HIV Western blotting.FindingsOur data suggested the existence of a significant cohort (n=429) of HIV antibody positive/viral load negative individuals. We systematically eliminated collection site bias, sample integrity, and viral genetic diversity as alternative explanations for undetectable viral loads. Mass spectroscopy unexpectedly detected the presence of 3TC antiviral medication in approximately 60% of those tested (209/354), and negative Western blot results indicated false positive serology in 12% (49/404). From the remaining Western blot positives (n=53) and indeterminates (n=31) with reactive Combo and rapid test results, we estimate 2.7-4.3% of infections in DRC to be potential elite controllers. We also analyzed samples from the DRC collected in 1987 and 2001-03, when antiretroviral drugs were not available, and found similarly elevated trends.InterpretationViral suppression to undetectable viral loads without therapy occurs infrequently in HIV-1 infected patients around the world. Mining of global data suggests a unique ability to control HIV infection arose early in central Africa and occurs in <1% of founder populations. Identification of this group of elite controllers presents a unique opportunity to study potentially novel genetic mechanisms of viral suppression.FundingAbbott Laboratories funded surveillance in DRC and subsequent research efforts. Additional funding was received from a MIZZOU Award from the University of Missouri. Research was supported in part by the Division of Intramural Research, National Institute of Allergy and Infectious Diseases, NIH.

Identification of Paraproteins via Serum Immunofixation or Serum Immunosubtraction and Immunoturbidimetric Quantitation of Serum Immunoglobulins in the Laboratory Testing for Monoclonal Gammopathies.

In laboratory testing for monoclonal gammopathies, paraproteins are identified via serum immunofixation or serum immunosubtraction, and immunoturbidimetric quantitation of serum immunoglobulins is often used. To evaluate methodologic differences between serum immunofixation and serum immunosubtraction, as well as in the quantitation of serum immunoglobulins on different clinical chemical platforms. Three hundred twenty-two unique routine patient samples were blinded and used for comparison between serum immunofixation on Sebia's HYDRASIS 2 and serum immunosubtraction on Sebia's CAPILLARYS 2, as well as between quantitation results of immunoglobulin A, G, and M on Abbott's ARCHITECT c16000PLUS and Roche's Cobas c 502 module. Microsoft Excel 2019 with the add-on Abacus 2.0 and MedCalc were used for statistical analysis and graphic depiction via bubble diagram, Passing-Bablok regressions, and Bland-Altman plots. The median age of patients was 75 years, and samples with paraproteinemia were nearly evenly split between sexes. Paraprotein identification differed remarkably between immunofixation and immunosubtraction. Quantitation of serum immunoglobulins showed higher values on Abbott's ARCHITECT c16000PLUS when compared with Roche's Cobas c 502 module. Identification of paraproteins via serum immunosubtraction is inferior to serum immunofixation, which can have implications on the diagnosis and monitoring of patients with monoclonal gammopathy. If immunoturbidimetric quantitation of immunoglobulins is used for follow-up, the same clinical-chemical platform should be used consistently.

SARS-CoV-2 seroprevalence among blood donors after the first COVID-19 wave in Canada.

BackgroundCase detection underestimates the burden of the COVID‐19 pandemic. Following the first COVID‐19 wave, we estimated the seroprevalence of severe acute respiratory syndrome coronavirus 2 (SARS‐CoV‐2) among blood donors across Canada.Study Design and MethodsThis serial cross‐sectional study was conducted between May 9 and July 21, 2020 from blood donors donating at all Canadian Blood Services locations. We used the Abbott Architect assay to detect SARS‐CoV‐2 IgG antibodies from retention plasma. Seroprevalence was standardized to population‐level demographics and assay characteristics were adjusted using the Rogan‐Gladen equation. Results were stratified by region, age, ethnicity, ABO groups, and quantiles of material and social deprivation indices. Temporal trends were evaluated at 2‐week intervals. Univariate and multivariate logistic regression compared SARS‐CoV‐2 reactive to non‐reactive donors by sociodemographic variables.ResultsOverall 552/74642 donors, had detectable antibodies, adjusted seroprevalence was 7.0/1000 donors (95% CI; 6.3, 7.6). Prevalence was differential by geography, Ontario had the highest rate, 8.8/1000 donors (7.8, 9.8), compared to the Atlantic region 4.5/1000 donors (2.6, 6.4); adjusted odds ratio (aOR) 2.2 (1.5, 3.3). Donors that self‐identified as an ethnic minority were more likely than white donors to be sero‐reactive aOR 1.5 (1.2, 1.9). No temporal trends were observed.DiscussionWorldwide, blood services have leveraged their operational capacity to inform public health. While >99% of Canadians did not show humoral evidence of past infection, we found regional variability and disparities by ethnicity. Seroprevalence studies will continue to play a pivotal role in evaluating public health policies by identifying trends and monitor disparities.

Hepatitis C virus core antigen as alternative diagnostic algorithm for active hepatitis C virus infection among haemodialysis population: Cost implications.

In Malaysia, majority anti-HCV positive haemodialysis patients do not undergo hepatitis C confirmation due to the high cost of HCV RNA. HCV Core Antigen might be a cost-effective diagnostic test to identify HD patients who have active HCV infection eligible for Direct Acting Anti-viral therapy. A cross-sectional study was conducted to assess the correlation between HCV Ag and HCV RNA and the cost implications of different diagnostic algorithms to diagnose active HCV infection using Anti-HCV, HCV Ag, and HCV RNA. Pre-dialysis blood was tested for both HCV Ag and HCV RNA. HCV Ag was tested with Abbott ARCHITECT HCV Ag test. Two-hundred twenty-seven haemodialysis patients were recruited from 20 centres with mean age of 57.68 ± 12.48 years, and male constitutes 56.8% (129) of the study population. HCV Ag correlated well with HCV RNA (Spearman test coefficient 0.943, p < .001) with sensitivity of 93.9%, specificity 99.3%, and the accuracy was 97.36%. Cost analysis indicated that a sequential test involving Anti-HCV antibody as initial screening, followed by HCV Ag on Anti-HCV positive and HCV RNA on HCV Ag negative cases translated to a modest cost-saving algorithm compared to standard diagnostic algorithm. HCV Ag correlated well with HCV RNA and can potentially be fused in an alternative diagnostic algorithm to generate cost savings methods to diagnose active HCV infection among haemodialysis patients. This alternative algorithm is especially relevant in low to middle-income countries such as Malaysia to optimize the use of the healthcare resource and gains in clinical outcomes.

Longitudinal evaluation of the Abbott ARCHITECT SARS-CoV-2 IgM and IgG assays in a pediatric population

BackgroundClinical laboratory testing has been an essential part of COVID-19 management. Serology can provide valuable information regarding a patient’s exposure to virus, and may have a larger role to play as vaccines becomes available. Limited data is available on the serological response in pediatric patients. Here we investigate the use of one manufacturer’s commercial assays for detecting IgM and IgG in an exclusively pediatric population. MethodsAbbott SARS-CoV-2 IgM and IgG assays were performed on an Abbott ARCHITECT i1000. For specificity studies, we tested 78 patient specimens collected before the COVID-19 pandemic, and 66 specimens from patients who tested negative for SARS-CoV-2 nucleic acid amplification test (NAAT) during the COVID-19 pandemic. For sensitivity we tested 181 specimens from 41 patients with a positive NAAT result. Precision data was acquired for 20 days. ResultsFor IgM, the highest qualitative positive agreement with molecular results was observed to be 15–30 days after a positive NAAT result or after symptom onset. For IgG, the highest positive agreement was 31–60 days after a positive NAAT result or 61–90 days after the start of symptoms. IgM started to decline 30 days after NAAT results and faded by 90 days. IgG started to decrease 60 days after a positive NAAT result. ConclusionThe Abbott IgM and IgG assays have negative agreements of 98.7–100% relative to NAAT results. The IgM and IgG levels assayed by these methods start to decline months after positive molecular results and onset of symptoms in a pediatric population.

Assessment of commercial SARS-CoV-2 antibody assays, Jamaica

BackgroundThe performance of the Roche Elecsys® Anti-SARS-CoV-2, Abbott Architect SARS-CoV-2 IgM, Abbott Architect SARS-CoV-2 IgG, Euroimmun SARS-CoV-2 IgA, Euroimmun SARS-CoV-2 IgG ELISA, and Trillium IgG/IgM rapid assays was evaluated in Jamaica. MethodsDiagnostic sensitivities of the assays were assessed by testing serum samples from SARS-CoV-2 PCR-confirmed persons and diagnostic specificity was assessed by testing serum samples collected during 2018–2019 from healthy persons and from persons with antibodies to a wide range of viral infections. ResultsSerum samples collected ≥14 days after onset of symptoms, or an initial SARS-CoV-2 RT-PCR positive test for asymptomatics, showed diagnostic sensitivities ranging from 67.9 to 75.0% when including all possible disease severities and increased to 90.0–95.0% when examining those with moderate to critical disease. Grouping moderate to critical disease showed a significant association with a SARS-CoV-2 antibody positive result for all assays. Diagnostic specificity ranged from 96.7 to 100.0%. For all assays examined, SARS-CoV-2 real-time PCR cycle threshold (Ct) values of the initial nasopharyngeal swab sample testing positive were significantly different for samples testing antibody positive versus negative. ConclusionsThese data from a predominantly African descent Caribbean population show comparable diagnostic sensitivities and specificities for all testing platforms assessed and limited utility of these tests for persons with asymptomatic and mild infections.

Longitudinal follow-up of IgG anti-nucleocapsid antibodies in SARS-CoV-2 infected patients up to eight months after infection.

BackgroundMost SARS-CoV-2 infected patients develop IgG antibodies within 2–3 weeks after symptom onset. Antibody levels have been shown to gradually decrease in the first months after infection, but few data are available at six months or later.MethodsA retrospective multi-center study was performed using 652 samples of 236 PCR-confirmed SARS-CoV-2 infected patients from 2 Belgian University hospitals. Patients were included if at least two samples were available (range 2–7 samples); including at least one sample collected 30 days or later after first positive PCR (range 0–240 days). Of those 236 patients, 19.1 % were classified as mild/asymptomatic (mild) and 80.9 % as moderate to critical (severe). IgG anti-nucleocapsid antibodies (anti-N) were measured using the Abbott Architect immunoassay.Results22.2 % of mild and 2.6 % of severe COVID-19 cases never seroconverted (p < 0.001). Of the mild patients who seroconverted 0–59 days after PCR; 18.8 %, 40.0 % and 61.1 % were seronegative in the windows 60–119 days, 120–179 days and 180–240 days after PCR, respectively. In severe patients, these numbers were 1.9 %, 10.8 % and 29.4 % respectively (p < 0.05 each). Antibody levels were significantly higher in severe patients compared to mild patients in each 60 day window (p < 0.001 each).ConclusionsSARS-CoV-2 anti-N IgG antibody levels steadily decreased after 2 months up to 8 months post PCR. Of severe COVID-19 patients, 70.6 % remained positive up to eight months after infection. Antibody levels were significantly lower in mild SARS-CoV-2 infected patients and 61.1 % became seronegative within 6 months after the first positive PCR.

Stringent thresholds in SARS-CoV-2 IgG assays lead to under-detection of mild infections

BackgroundThresholds for SARS-CoV-2 antibody assays have typically been determined using samples from symptomatic, often hospitalised, patients. In this setting the sensitivity and specificity of the best performing assays can both exceed 98%. However, antibody assay performance following mild infection is less clear.MethodsWe assessed quantitative IgG responses in a cohort of healthcare workers in Oxford, UK, with a high pre-test probability of Covid-19, in particular the 991/11,475(8.6%) who reported loss of smell/taste. We use anosmia/ageusia and other risk factors as probes for Covid-19 infection potentially undiagnosed by immunoassays by investigating their relationship with antibody readings either side of assay thresholds.ResultsThe proportion of healthcare workers reporting anosmia/ageusia increased at antibody readings below diagnostic thresholds using an in-house ELISA (n = 9324) and the Abbott Architect chemiluminescent microparticle immunoassay (CMIA; n = 11,324): 426/906 (47%) reported anosmia/ageusia with a positive ELISA, 59/449 (13.1%) with high-negative and 326/7969 (4.1%) with low-negative readings. Similarly, by CMIA, 518/1093 (47.4%) with a positive result reported anosmia/ageusia, 106/686 (15.5%) with a high-negative and 358/9563 (3.7%) with a low-negative result. Adjusting for the proportion of staff reporting anosmia/ageusia suggests the sensitivity of both assays in mild infection is lower than previously reported: Oxford ELISA 89.8% (95%CI 86.6–92.8%) and Abbott CMIA 79.3% (75.9–82.7%).ConclusionFollowing mild SARS-CoV-2 infection 10–30% of individuals may have negative immunoassay results. While lowered diagnostic thresholds may result in unacceptable specificity, our findings have implications for epidemiological analyses and result interpretation in individuals with a high pre-test probability. Samples from mild PCR-confirmed infections should be included in SARS-CoV-2 immunoassay evaluations.

Multiple Biomarker Approach to Risk Stratification in COVID-19

Multiple Biomarker Approach to Risk Stratification in COVID-19

Familial Dysalbuminemic Hyperthyroxinemia as a Cause for Discordant Thyroid Function Tests

IntroductionDiscordant thyroid function tests are routinely encountered in clinical practice. Differential diagnoses include acute thyroxine (T4) ingestion, laboratory interference from heterophilic antibodies, thyroid hormone resistance, thyroid-stimulating hormone (TSH)-secreting pituitary adenomas, and T4 protein binding abnormalities. The impact of abnormal binding proteins may be less recognized since widespread use of free T4 (FT4) assays compared to older total T4 assays.Case reportA 69-year-old female was referred for assessment of discordant thyroid function tests. Biochemistry since July 2015 showed persistently elevated FT4 levels by immunoassay ranging between 25 to 34 pmol/L with normal or slightly decreased TSH ranging between 0.05 to 2.74 mU/L. The patient was clinically euthyroid on 100 mcg daily of levothyroxine for Hashimoto’s thyroiditis. FT4 measured using liquid chromatography-tandem mass spectrometry (LC-MS/MS) was 19.5 pmol/L. Exome sequencing (confirmed by Sanger sequencing) detected a guanine to adenine substitution at residue 725 of the ALB gene previously associated with dysalbuminemic hyperthyroxinemia. The patient’s daughter had similar thyroid function tests and the same genetic variant. FT4 results from 3 different automated immunoassays showed the Roche Cobas and Siemens Centaur platforms to be most affected by the variant, and Abbott Architect had the best agreement with LC-MS/MS.ConclusionFamilial dysalbuminemic hyperthyroxinemia is a potential cause of discordant thyroid function tests. Clinicians suspecting protein-binding abnormalities may further investigate using reference methods such as LC-MS/MS and equilibrium dialysis if available. The increasing accessibility of exome sequencing offers a cost-effective method of diagnosing genetic variants that cause discordant thyroid function tests.

Life Sciences Discovery and Technology Highlights

Serological severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) assays are urgently needed for diagnosis, for contact tracing, and for epidemiological studies. So far, there are limited data on how recently commercially available high-throughput immunoassays, using different recombinant SARS-CoV-2 antigens, perform with clinical samples. Focusing on immunoglobulin G (IgG) and total antibodies, Kohmer et al. demonstrate the performance of four automated immunoassays—the Abbott Architect i2000 (N protein based), Roche cobas e 411 analyzer (N protein based, not differentiating between IgA, IgM, or IgG antibodies), LIAISON XL platform (S1 and S2 protein based), and VIRCLIA automation system (S1 and N protein based)—in comparison to two enzyme-linked immunosorbent assays (ELISAs) (Euroimmun SARS-CoV-2 IgG, S1 protein based; and Virotech SARS-CoV-2 IgG ELISA, N protein based) and an in-house–developed plaque reduction neutralization test (PRNT).

Performance of two rapid point of care SARS-COV-2 antibody assays against laboratory-based automated chemiluminescent immunoassays for SARS-COV-2 IG-G, IG-M and total antibodies

IntroductionWe evaluated two SARS-CoV-2 antibody point-of-care tests (POCTs) (Abbott Panbio COVID-19 IgG/IgM and Roche SARS-CoV-2 Rapid Antibody tests) and compared the results to their respective chemiluminescent immunoassays (CLIAs) (Abbott Architect IgM, Architect IgG, Roche Cobas total antibody assays). Method200 pre-pandemic sera and 48 samples positive for various conditions (18 viral hepatitis, 18 dengue, 11 ANA and 1 dsDNA) were used as controls and to assess for cross-reactivity. Anonymised residual leftover sera positive for SARS-CoV-2 on RT-PCR were recruited as cases (n ​= ​133). The sensitivity/specificity/cross-reactivity/positive predictive value (PPV)/negative predictive value (NPV) of the POCTs were assessed. Concordance between the POCTs and chemiluminescent immunoassays (CLIAs) were analysed. ResultsAbbott/Roche POCT specificity was 98.7%/100% (95% CI 96.5–99.8/98.5–100) and sensitivity was 97.2%/97.2% (95% CI 85.5–99.9/85.5–99.9) in cases ≥14 days post-first positive RT-PCR (POS), PPV was 68.7%/100% (95% CI 41.3–87.2/94.7–100.0), and NPV was 97.4%/97.6% (95% CI 97.0–97.8/97.2–98.0). In cases ≥14 days POS, concordance of Abbott/Roche POCT and CLIAs was 97.2%/100% (35/36 and 36/36 results). The sensitivity of individual IgM-band results on both POCTs did not increase >95% even after 14 days POS (Abbott 2.78%, Roche 44.4%). ConclusionBoth POCTs have good specificity, little cross-reactivity with other antibodies, and sensitivity >95% when used in subjects ≥14 days POS. Analysis of individual POCT IgG/IgM-bands did not provide any additional information. POCTs can substitute for CLIAs in cases ≥14 days POS. In low prevalence areas, POCTs would be especially useful when combined with antigen testing in an orthogonal format to increase the PPV of COVID-19 results.

Clinical Evaluation of a New High-Sensitivity Cardiac Troponin I Assay for Diagnosis and Risk Assessment of Patients with Suspected Acute Myocardial Infarction

Introduction: Current assays based on the 0-hour/1-hour (0-/1-h) algorithm using high-sensitivity cardiac troponin (hs-cTn) are limited to only Abbott Architect hs-cTnI, Siemens Vista hs-cTnI, and Roche Elecsys hs-cTnT. Objective: This study aimed to evaluate this new hs-cTnI assay, LumipulsePresto hs Troponin I, for diagnosis of acute myocardial infarction (AMI) on admission and on 0-/1-h algorithm to stratify AMI patients precisely. Methods: This prospective cohort study included 442 patients with suspected non-ST-elevation myocardial infarction in three hospitals in Japan and Taiwan from June 2016 to January 2019. We enrolled patients presenting to the emergency department with symptoms suggestive of AMI and collected blood samples on admission and 1 hour later. Two independent cardiologists centrally adjudicated final diagnoses; all clinical information was reviewed twice: first, using serial hs-cTnT (Roche-Elecsys, primary analysis) and Lumipulse Presto Lumipulse Presto, second, using the Lumipulse Presto hs-cTnI measurements. At first, we compared diagnostic accuracy quantified using receiver operating characteristic (ROC) curves for AMI. Then, we evaluated major adverse cardiovascular events (cardiac death, AMI) in the rule-out group according to a 0-hour/1-hour algorithm at the 30-day follow-up. Results: Diagnostic accuracy at presentation by the ROC curve for AMI was very high and similar for the LumipulsePresto hs-cTnI and hs-cTnT,(area under the curve [AUC]: LumipulsePresto hs-cTnI, 0.89, 95% confidence interval [CI] 0.86–0.93; hs-cTnT, 0.89, 95% CI 0.85–0.93; p = 0.82). In early presenters, the LumipulsePresto hs-cTnI appeared to maintain the diagnostic performance of hs-cTn for patients with <3 h (AUC: LumipulsePresto hs-cTnI, 0.87, 95% CI 0.81–0.92; hs-cTnT, 0.86, 95% CI 0.80–0.92; p = 0.81). The algorithm using the LumipulsePresto hs-cTnI ruled out AMI in 200 patients with negative predictive value and sensitivity of 100% (95% CI 97.3%–100%) and 100% (95% CI 92.7%–100%), respectively, in the rule-out group. Conclusion: Diagnostic accuracy and clinical utility of the novel LumipulsePresto hs-cTnI assay are high and comparable with the established hs-cTn assays.

Plasma hemoglobin: A method comparison of six assays for hemoglobin and hemolysis index measurement

Plasma hemoglobin (Hb) is measured for assessment of in vivo and in vitro hemolysis. The objective of the present investigation was to conduct a method comparison of five quantitative and one semi-quantitative Hb and H-index (hemolysis index) assays to evaluate their performance measuring plasma Hb in clinical specimens. One hundred and fourteen clinical specimens previously tested for plasma Hb using a laboratory-developed spectrophotometric assay were also tested for Hb using a HemoCue Plasma/Low Hb assay (azide methemoglobin), a laboratory-modified Pointe Scientific Hb assay (cyanmethemoglobin), tested for H-index measurements using a Roche cobas c501, an Abbott Architect c8000, and a semi-quantitative (binned) H-index measurement on a Beckman AU5800. The reference result was defined as the median Hb score (median of all Hb or H-index results). The laboratory-developed spectrophotometric Hb assay and Roche H-index methods mostly closely matched the median Hb score across all data, as well as for lower range median Hb score results ≤2.0g/L. Two-way frequency table analysis using an Hb (or H-index) cutoff of 0.5g/L (or 0.5 H-index units) was then performed to compare methods to the median Hb score cutoff. The Beckman method had the highest accuracy at this cutoff, the Roche and Abbott methods had the highest positive predictive value (PPV), and the Beckman, HemoCue, and Pointe methods had the highest negative predictive value (NPV). Plasma Hb and H-index results vary by method. Laboratories should evaluate the performance characteristics of their respective assays when considering adoption of spectrophotometric or chemical methods for plasma Hb assessment.

The effect of haemolysis on the direct and indirect ion selective electrode measurement of sodium.

We compared the effect of haemolysis in sodium measurement using indirect and direct ion-selective electrodes to test the hypothesis that haemolytic effect on sodium would be greater with indirect ion-selective electrode due to electrolyte exclusion effect from released intracellular proteins. Plasma lithium heparin samples (n = 36) from four volunteers were prepared to give a range of haemolytic indices (H-indices). Samples were analysed for sodium by indirect ion-selective electrode, H-index and total protein on an Abbott Architect c16000 and sodium by direct ion-selective electrode on a Siemens RAPIDPoint 500. Percentage changes in sodium in paired direct and indirect ion-selective electrode values were compared. Abbott H-index, which represents haemoglobin concentration in g/L, correlated with percentage negative change in sodium by direct ion-selective electrode (ρ 0.995, P < 0.001) and indirect ion-selective electrode (ρ 0.991, P < 0.001). Percentage negative change was less when sodium was measured by direct ion-selective electrode compared to indirect ion-selective electrode (Wilcoxon signed-rank Z = 3.46, P = 0.01). The difference in percentage change in sodium between direct ion-selective electrode and indirect ion-selective electrode correlated with total protein (ρ 0.751, P < 0.001). The negative bias in sodium results exceeded the reference change value of 2.2% at an H-index of 8.31 for indirect ion-selective electrode and 9.26 for direct ion-selective electrode. Haemolysis causes negative influence with sodium measured by both indirect and direct ion-selective electrode due to a dilutional hyponatremia. The additional interference in indirect ion-selective electrode is due to the electrolyte exclusion effect but this is unlikely to be clinically significant as it is small in magnitude.

Comparison of GFAP and UCH-L1 Measurements from Two Prototype Assays: The Abbott i-STAT and ARCHITECT Assays.

Glial fibrillary acidic protein (GFAP) and ubiquitin carboxyl-terminal hydrolase L1 (UCH-L1) may aid in the evaluation of traumatic brain injury (TBI). The objective of this analysis was to compare GFAP and UCH-L1 values measured using a handheld device compared with a core laboratory platform. We analyzed plasma samples from patients with TBI and healthy controls enrolled in the Transforming Research and Clinical Knowledge in TBI (TRACK-TBI) cohort study. GFAP and UCH-L1 were measured twice in each subject using prototype assays, first with the Abbott i-STAT™ handheld device, and second with the Abbott ARCHITECT® platform. We then quantified the agreement in biomarker values obtained using these two methods. GFAP and UCH-L1 were measured twice in 570 and 572 samples, respectively. GFAP values measured by the ARCHITECT platform (median 143.3 [interquartile range (IQR): 19.8–925.8] pg/mL) were higher than values measured by the i-STAT (median 116.0 [IQR: 9.2–856.5] pg/mL). GFAP values from the two platforms were strongly correlated (p = 0.985). Similarly, UCH-L1 values measured by the ARCHITECT platform (median 163.9 [IQR: 82.5–412.4] pg/mL) were higher than values measured by the i-STAT (median 122.5 [IQR: 63.0–297.3] pg/mL). UCH-L1 values from the two platforms were strongly correlated (p = 0.933). Passing-Bablok regression equations were developed to estimate the relationship between the two platforms, specifically to predict i-STAT values from the ARCHITECT platform. GFAP and UCH-L1 values measured using the prototype assays on the Abbott i-STAT and ARCHITECT platforms are strongly correlated and values from either platform may be converted to the other.

Longitudinal Study of the Signal Strength in two Serologic Assays for Detection of SARS-CoV-2 Specific Antibodies.

In the course of the current SARS-CoV-2 pandemic, antibody assays provide an important means for guidance of public health efforts. Thus, characterization of the course of antibody signals on different widely used assays is needed. We selected 25 PCR-confirmed SARS-CoV-2 cases among 3,273 healthcare workers and measured the course of the antibody signal using the Abbott Architect SARS-CoV-2 IgG assay and the Roche Elecsys® Anti-SARS-CoV-2 immunoassay. The signal strength was then modelled using linear mixed models adjusted for age. Since first sampling, the assay signal decreased per day in the Abbott assay (standardized slope (β) = -0.46, 95% CI = -0.54 to -0.39). In contrast, an increase in the signal was ascertained by the Roche immunoassay per day (β = 0.25, 95% CI = 0.09 to 0.41). Roche Elecsys® Anti-SARS-CoV-2 immunoassay may exhibit greater sensitivity in detecting SARS-CoV-2-specific antibodies in individuals in late stages of postinfection.

Moving ahead in HCV diagnostics: Need for the introduction of HCV core antigen assay in low and middle-income countries

Hepatitis C virus (HCV) infections are associated with significant morbidity and mortality globally. The diagnosis of HCV is primarily based on indirect serological assays such as enzyme-linked immunosorbent assay (ELISA), chemiluminescence immunoassay (CIA), and rapid diagnostic tests to detect HCV antibodies. Direct tests detect/quantify components of HCV virions, such as HCV ribonucleic acid (RNA) (nucleic acid test or nucleic acid amplification test [NAT]) and HCV core antigen (HCVcAg). The HCVcAg assay (CIA, Abbott ARCHITECT) is an immune assay used for the quantitative determination of the HCVcAg. This test is simple and fast with the potential to be incorporated into diagnostic guidelines and be used in combination with anti-HCV (CIA) as an effective screening test. HCVcAg can also be used as a potential biomarker for treatment initiation and monitoring patients to assess the treatment response. Apart from this, the scope for implementation of the HCVcAg assay in resource limited setting lies in screening of immune compromised patients where anti-HCV serology is not dependable. However, concerns related to lower sensitivity compared to HCV RNA do exist. Nevertheless, the HCVcAg assay can make a significant difference in the measures taken for the control and eradication of hepatitis C and its complications in India.