Abbott Architect Research Articles

Seroprevalence of Anti-SARS-CoV-2 Antibodies in Blood Donors from Nuevo Leon State, Mexico, during 2020: A Retrospective Cross-Sectional Evaluation.

The progression and distribution of the SARS-CoV-2 pandemic are continuously changing over time and can be traced by blood donors’ serological survey. Here, we investigated the seroprevalence of anti-SARS-CoV-2 antibodies in blood donors in Nuevo Leon, Mexico during 2020 as a strategy for the rapid evaluation of the spread of SARS-CoV-2 and asymptomatic case detection. We collected residual plasma samples from blood donors who attended two regional donation centers from January to December of 2020 to identify changes in anti-SARS-CoV-2 IgG prevalence. Plasma samples were analyzed on the Abbott Architect instrument using the commercial Abbott SARS-CoV-2 IgG chemiluminescent assay. We found a total of 99 reactive samples from 2068 analyzed plasma samples, resulting in a raw prevalence of 4.87%. Donors aged 18–49 years were more likely to be seropositive compared to those aged >50 years (p < 0.001). Weekly seroprevalence increased from 1.8% during the early pandemic stage to 27.59% by the end of the year. Prevalence was 1.46-fold higher in females compared to males. Case geographical mapping showed that Monterrey city recorded the majority of SARS-CoV-2 cases. These results show that there is a growing trend of seroprevalence over time associated with asymptomatic infection that is unnoticed under the current epidemiological surveillance protocols.

Antibodies to Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2) in All of Us Research Program Participants, 2 January to 18 March 2020.

BackgroundWith limited severe acute respiratory syndrome coronavirus (SARS-CoV-2) testing capacity in the United States at the start of the epidemic (January–March 2020), testing was focused on symptomatic patients with a travel history throughout February, obscuring the picture of SARS-CoV-2 seeding and community transmission. We sought to identify individuals with SARS-CoV-2 antibodies in the early weeks of the US epidemic.MethodsAll of Us study participants in all 50 US states provided blood specimens during study visits from 2 January to 18 March 2020. Participants were considered seropositive if they tested positive for SARS-CoV-2 immunoglobulin G (IgG) antibodies with the Abbott Architect SARS-CoV-2 IgG enzyme-linked immunosorbent assay (ELISA) and the EUROIMMUN SARS-CoV-2 ELISA in a sequential testing algorithm. The sensitivity and specificity of these ELISAs and the net sensitivity and specificity of the sequential testing algorithm were estimated, along with 95% confidence intervals (CIs).ResultsThe estimated sensitivities of the Abbott and EUROIMMUN assays were 100% (107 of 107 [95% CI: 96.6%–100%]) and 90.7% (97 of 107 [83.5%–95.4%]), respectively, and the estimated specificities were 99.5% (995 of 1000 [98.8%–99.8%]) and 99.7% (997 of 1000 [99.1%–99.9%]), respectively. The net sensitivity and specificity of our sequential testing algorithm were 90.7% (97 of 107 [95% CI: 83.5%–95.4%]) and 100.0% (1000 of 1000 [99.6%–100%]), respectively. Of the 24 079 study participants with blood specimens from 2 January to 18 March 2020, 9 were seropositive, 7 before the first confirmed case in the states of Illinois, Massachusetts, Wisconsin, Pennsylvania, and Mississippi.ConclusionsOur findings identified SARS-CoV-2 infections weeks before the first recognized cases in 5 US states.

Blood group O convalescent plasma donations have significantly lower levels of SARS-CoV-2 IgG antibodies compared to blood group A donations.

BackgroundCOVID‐19 convalescent plasma (CCP) is plasma collected from individuals who have recovered from SARS‐CoV‐2 infection. The FDA Emergency Use Authorization restricts use of CCP to high‐titer units only. The purpose of this study was to determine if donor ABO blood group was associated with SARS‐CoV‐2 antibody response, and subsequent qualification as high‐titer CCP.MethodsAll CCP donations collected from April 21, 2020 to September 1, 2020 were included. The Abbott ARCHITECT semi‐quantitative chemiluminescent microparticle immunoassay was used to assess IgG antibodies to the nucleocapsid protein of SARS‐CoV‐2. Units with a S/C value ≥4.5 were considered high titer.ResultsA total of 232 CCP donations were evaluated. There were no significant differences in the distribution of sex, age, and interval from symptom resolution to donation by ABO blood group. The mean SARS‐CoV‐2 IgG antibody S/C value was significantly lower in blood group O donations (3.6), compared to blood group A (5.0) donations (p < .001). There was no difference in antibody response between the other blood group pairings. Blood group O donations resulted in a lower percentage of high‐titer units (35%), compared to blood group A (60%), B (58%), and AB (65%) donations.ConclusionBlood group O donations were found to have significantly lower levels of SARS‐CoV‐2 IgG nucleocapsid antibodies compared to blood group A donations and were less likely to produce CCP units that qualified as high titer. These findings may aid donor recruitment to promote availability of high‐titer CCP to meet patient needs.

Biotin Interference in Assays for Thyroid Hormones, Thyrotropin and Thyroglobulin.

Background: Biotin has been reported to interfere with several commonly used laboratory assays resulting in misleading values and possible erroneous diagnosis and treatment. This report describes a prospective study of possible biotin interference in thyroid-related laboratory assays, with a comparison of different commonly used assay platforms. Materials and Methods: Thirteen adult subjects (mean age 45 ± 13 years old) were administered biotin 10 mg/day for eight days. Blood specimens were collected at three time points on day 1 and on day 8 (baseline, two, and five hours after biotin ingestion). Thyrotropin (TSH), free triiodothyronine (fT3), free thyroxine (fT4), total triiodothyronine (TT3), total thyroxine (TT4), thyroxine binding globulin (TBG), and thyroglobulin (Tg) levels were analyzed with four different platforms: Abbott Architect, Roche Cobas 6000, Siemens IMMULITE 2000, and liquid chromatography with tandem mass spectrometry (LC-MS/MS). TSH, fT3, fT4, TT3, and TT4 were measured with Abbott Architect and Roche Cobas 6000. fT3, fT4, TT3, and TT4 were also measured by LC-MS/MS. Tg was measured by Siemens IMMULITE 2000. TBG was assessed with Siemens IMMULITE 2000. Results: Significant changes in TSH, fT4, and TT3 measurements were observed after biotin exposure when the Roche Cobas 6000 platform was used. Biotin intake resulted in a falsely lower Tg level when measurements were performed with Siemens IMMULITE 2000. At the time points examined, maximal biotin interference was observed two hours after biotin exposure both on day 1 and day 8. Conclusions: A daily dose of 10 mg was shown to interfere with specific assays for TSH, fT4, TT3, and Tg. Physicians must be aware of the potential risk of erroneous test results in subjects taking biotin supplements. Altered test results for TSH and Tg can be particularly problematic in patients requiring careful titration of levothyroxine therapy such as those with thyroid cancer.

Pediatric reference interval verification for common biochemical assays on the Abbott Alinity system.

The quality of clinical laboratory service depends on quality laboratory operations and accurate test result interpretation based on reference intervals (RIs). As new analytical systems continue to be developed and improved, previously established RIs must be verified. The Canadian Laboratory Initiative on Pediatric Reference Intervals (CALIPER) has established comprehensive RIs for many biomarkers on several analytical systems. Here, published CALIPER RIs for 28 chemistry assays on the Abbott ARCHITECT were assessed for verification on the newer Alinity system. An analytical validation was first completed to assess assay performance. CALIPER serum samples (100) were analyzed for 28 chemistry assays on the Alinity system. The percentage of results falling within published pediatric ARCHITECT reference and confidence limits was determined for each analyte. Based on Clinical and Laboratory Standards Institute (CLSI) guidelines, if≥90% of test results fell within confidence limits of ARCHITECT assay RIs, they were considered verified. Of the 28 assays assessed, 26 met the criteria for verification. Reference values for calcium and magnesium did not meet the criteria for verification with 87% and 35% falling within previously established ARCHITECT confidence limits, respectively. However, both assays could be verified using pediatric RIs provided in the Abbott Alinity package insert. In this study, CALIPER ARCHITECT RIs were verified on the Alinity system for several chemistry assays. These data demonstrate excellent concordance for most assays between the Abbott ARCHITECT and Alinity systems and will assist in the implementation of the Alinity system in pediatric healthcare institutions.

Biochemical assessment of adequate levothyroxine replacement in primary hypothyroidism differs with different TSH assays: potential clinical implications

AimThyroid stimulating hormone (TSH) assays provided by Abbott Laboratories and Roche Diagnostics are used by approximately 75% of laboratories in the UK. We assessed the potential impact of Abbott and...

Urine toxicology screening by liquid chromatography time-of-flight mass spectrometry in a quaternary hospital setting

ObjectiveValidation of a non-targeted method for urine drug screening (UDS) by liquid chromatography quadrupole time-of-flight mass spectrometry (LC-QTOF), and comparison to an established GC–MS method in a hospital setting. Methods217 UDS specimens sent to a quaternary hospital pathology department, were analysed by a CEDIA® immunoassay screen (six drug panels; amphetamines, barbiturates, benzodiazepines, cocaine metabolites, cannabinoids and opiates) on an Abbott Architect instrument. Specimens were subsequently analysed by an established non-targeted qualitative GC–MS method and results compared with a general unknown screening method by LC-QTOF that was under evaluation as a replacement method. Results42 selected drugs were evaluated; limits of identification ranged from 2 to 100 µg/L and most drugs (n = 39) were stabile for 24 h after preparation. Matrix effects greater than 25% were observed in seven of the selected drugs. 87% of the specimens tested positive to 1 or more drug panels in a CEDIA® screen. A total of 537 positive drug findings were identified by GC–MS compared to 1,267 positive findings by LC-QTOF. On average, each GC–MS screen identified 2.5 ± 1.8 drugs and the LC-QTOF screen identified 5.8 ± 3.2 drugs. No drugs were identified in 11.3% of the GC–MS screens, whereas drugs were detected in 99% of these by the LC-QTOF. In almost all instances, the LC-QTOF screen could provide mass spectrometric confirmatory results of positive immunoassay screens and was able to identify a wider range of additional drugs and drug metabolites. ConclusionsThe described general unknown screening (non-targeted, qualitative) LC-QTOF method can detect a larger range of drugs encountered in a hospital setting. The method has been shown to be suitable for comprehensive toxicology screening in a clinical toxicology laboratory.

The Clinical Significance and Utility of Routine Screening for Macroprolactin in Patients With Hyperprolactinemia

Background: Macroprolactin is a complex of monomeric prolactin (PRL) molecules with immunoglobulin G (IgG) that can result in the elevation of serum prolactin level. Macroprolactin is biologically less active and failure to screen for macroprolactin may lead to unnecessary investigations and treatments in patients with hyperprolactinaemia. Aim: We sought to evaluate the clinical significance and clinical utility of routine screening of macroprolactin in patients with hyperprolactinemia. Methods: We analysed 141 patients from a retrospective database of patients with elevated serum prolactin in Changi General Hospital from Jan 2017 to Dec 2019 with routine screening of macroprolactin with polyethylene glycol (PEG) precipitation using Abbott Architect Prolactin assay. Clinical, biochemical, radiological data and medication usage were extracted from electronic medical records. Macroprolactinaemia was defined as a PRL recovery of < 60%. Approval was obtained from the local research ethics committee. Results: Thirty-six (26%) patients had macroprolactinaemia with a male predominance (72%). There were no significant differences in the presence of symptoms, the percentages of medication-induced hyperprolactinemia, and magnetic resonance imaging (MRI) pituitary scans done between patients with macroprolactinaemia and those with truly elevated serum prolactin. As such clinical features might not be useful to differentiate patients with macroprolactinaemia. Eight MRI pituitary scans were performed in patients with macroprolactinaemia and pituitary abnormalities were detected in 4 of the patients which are likely non-functioning pituitary lesions. As such, not only were unnecessary scans done but it also led to a cascade of further investigations. Eight patients had simultaneous macroprolactinaemia and elevated bioactive serum prolactin, as such post-PEG prolactin level with corresponding reference ranges rather than the percentage recovery should be use as the threshold for defining macroprolactinaemia to avoid misdiagnosis. Conclusion: Macroprolactinaemia is common and routine screening may avert unnecessary investigations. Post-PEG prolactin level with corresponding reference ranges should be used as diagnostic threshold.

Cross-Institutional Evaluation of the Abbott ARCHITECT SARS-CoV-2 IgG Immunoassay.

ObjectiveTo describe a cross-institutional approach to verify the Abbott ARCHITECT SARS-CoV-2 antibody assay and to document the kinetics of the serological response.MethodsWe conducted analytical performance evaluation studies using the Abbott ARCHITECT SARS-CoV-2 antibody assay on 5 Abbott ARCHITECT i2000 automated analyzers at 2 academic medical centers.ResultsWithin-run and between-run coefficients of variance (CVs) for the antibody assay did not exceed 5.6% and 8.6%, respectively, for each institution. Quantitative and qualitative results agreed for lithium heparin plasma, EDTA-plasma and serum specimen types. Results for all SARS-CoV-2 IgG-positive and -negative specimens were concordant among analyzers except for 1 specimen at 1 institution. Qualitative and quantitative agreement was observed for specimens exchanged between institutions. All patients had detectable antibodies by day 10 from symptom onset and maintained seropositivity throughout specimen procurement.ConclusionsThe analytical performance characteristics of the Abbott ARCHITECT SARS-CoV-2 antibody assay within and between 2 academic medical center clinical laboratories were acceptable for widespread clinical-laboratory use.

Seroprevalence of SARS-CoV-2 antibodies in university students: Cross-sectional study, December 2020, England

BackgroundIn England, the reopening of universities in September 2020 coincided with a rapid increase in SARS-CoV-2 infection rates in university aged young adults. This study aimed to estimate SARS-CoV-2 antibody prevalence in students attending universities that had experienced a COVID-19 outbreak after reopening for the autumn term in September 2020.MethodsA cross-sectional serosurvey was conducted during 02–11 December 2020 in students aged ≤ 25 years across five universities in England. Blood samples for SARS-CoV-2 antibody testing were obtained using a self-sampling kit and analysed using the Abbott SARS-CoV-2 N antibody and/or an in-house receptor binding domain (RBD) assay.FindingsSARS-CoV-2 seroprevalence in 2,905 university students was 17.8% (95%CI, 16.5–19.3), ranging between 7.6%-29.7% across the five universities. Seropositivity was associated with being younger likely to represent first year undergraduates (aOR 3.2, 95% CI 2.0–4.9), living in halls of residence (aOR 2.1, 95% CI 1.7–2.7) and sharing a kitchen with an increasing number of students (shared with 4–7 individuals, aOR 1.43, 95%CI 1.12–1.82; shared with 8 or more individuals, aOR 1.53, 95% CI 1.04–2.24). Seropositivity was 49% in students living in halls of residence that reported high SARS-CoV-2 infection rates (>8%) during the autumn term.InterpretationDespite large numbers of cases and outbreaks in universities, less than one in five students (17.8%) overall had SARS-CoV-2 antibodies at the end of the autumn term in England. In university halls of residence affected by a COVID-19 outbreak, however, nearly half the resident students became infected and developed SARS-CoV-2 antibodies.

Diagnostic accuracy of three SARS-CoV2 antibody detection assays, neutralizing effect and longevity of serum antibodies

Evidence is currently insufficient to know whether SARS-CoV-2 antibodies (Abs) protect from future infection and how long immunity will last. The kinetics of the immune response to SARS-CoV-2 infection and role of serology in estimating individual protective immunity is yet to be established. We evaluated diagnostic performances of three serological assays - Abbott Architect CMIA IgG, bioMerieux VIDAS ELFA IgG/IgM, and Diesse Chorus ELISA IgG/IgM, and analyzed longevity and potential neutralizing effect of SARS-CoV-2 Abs in COVID-19 patients. Clinical sensitivities of assessed IgG tests two to three weeks post symptom onset (PSO) were very high: 96.77 % for Architect, 96.77 % for Chorus, and 100.00 % for VIDAS. Sensitivities of two assessed IgM assays were moderate: 74.07 % for Chorus, and 76.92 % for VIDAS. Specificities were excellent for all assessed IgG assays: 99.01 % for Architect and 100 % for Chorus and VIDAS. Chorus and VIDAS IgM assays also achieved excellent specificity of 99.01 % and 100 %, respectively. In most cases IgG Abs were still present eight months PSO. Neutralizing antibodies were detected in majority of serum samples from convalescent patients. Serum samples from severe COVID-19 patients had higher antibody titers and higher neutralizing activity. We observed a strong positive correlation among SARS-CoV-2 IgG antibody titer and neutralizing activity. The strongest positive correlation to neutralizing activity was found for VIDAS IgG assay.

Heterogenous Serological Responses to BNT162b2 mRNA Vaccine in Patients with Haematological Malignancies

Background: Patients with active haematological malignancies (HM) have been excluded from clinical trials evaluating vaccines against SARS-CoV-2. Both HM and their treatments are commonly immunosuppressive and are likely to impact COVID-19 vaccine efficacy.Methods: We performed a study assessing serological response to one and two BNT162b2 vaccine doses in healthy healthcare workers (HCWs) and in patients with HM. Peripheral blood samples were collected at three time points: 0-10 days before the first BNT162b2 vaccine jab, on the day of second jab (around day 21) and 7 to 21 days after the second jab. Abbott Architect SARS-CoV-2 IgG Quant II assay was used to quantify serum anti-SARS-CoV-2-S1 IgG antibody (anti-S1 IgG) levels. HM individuals were stratified into groups by current or most recent treatment, latency since treatment and anti-S1 IgG seroconversion status before the first jab.Results: 653 anti-S1 IgG negative participants with HM (median age 64 years, IQR 53 - 72, 52% female) and 69 healthy HCWs (40 [32 - 53] years, 83% female) were included in the study. 18-60 year-old HM patients had lower median anti-S1 IgG response (median 6810 [IQR 635 - 20574] vs 21394 [14289 - 33322], pConclusion: Patients with HM mount blunted and heterogeneous antibody responses to full course of BNT162b2 mRNA vaccination. Patients actively treated with BTKi, ruxolitinib and anti-CD20 therapies appear to be the most negatively affected and may be left unprotected from COVID-19 infection. Regardless of seroconversion status before vaccination, many HM patients improve their serologic responses after the second BNT162b2 jab at 3 weeks.Funding Statement: This research is funded by the sponsor of our study - Vilnius University Hospital Santaros Klinikos.Declaration of Interests: We declare no competing interests.Ethics Approval Statement: The study was approved by the Vilnius Regional Bioethics Committee (approval No. 2021/3-1331-803).

Early Diagnosis of HIV-1 and HIV-2 Using Cobas HIV-1/HIV-2 Qualitative Test: A Novel Qualitative Nucleic Acid Amplification Test for Plasma, Serum, and Dried Blood Spot Specimens.

Background:Nucleic acid amplification tests (NATs) minimize the time from HIV infection to diagnosis, reducing transmission during acute HIV. NATs are especially useful for diagnosing HIV in children younger than 18 months and discriminating between HIV-1 and HIV-2.Methods:We evaluated the performance of the cobas HIV-1/HIV-2 qualitative (cobas HIV-1/2 Qual) test for use on cobas 6800/8800 Systems. The results of adult plasma and serum samples and pediatric dried blood spots were compared with those of the recomLine HIV-1 & HIV-2 Immunoglobulin G serological test and COBAS AmpliPrep/COBAS TaqMan HIV-1 qualitative test, v2.0. Genotype inclusivity and limits of detection were determined, and sensitivity on seroconversion panels was compared with that in the Bio-Rad Geenius HIV 1/2 Confirmatory Assay, Abbott ARCHITECT HIV Ag/Ab Combo serological test, and cobas TaqScreen MPX, v2.0.Results:Concordance of cobas HIV-1/2 Qual test with the comparator serological test and COBAS AmpliPrep/COBAS TaqMan test was ≥99.6% with all sample types. Reactivity with all HIV genotypes was 100%. LOD in plasma samples was 14.8, 12.6, and 27.9 copies/mL for HIV-1 group M, HIV-1 group O, and HIV-2, respectively, with similar results for serum samples. LOD in dried blood spots was 255 copies/mL for HIV-1 and 984 copies/mL for HIV-2. HIV infection was detected 18.9 days and 8.5 days earlier than the confirmatory and serological assays, respectively, and at a similar time to the NAT.Conclusions:The cobas HIV-1/2 Qual test enables early and accurate diagnoses of HIV-1 and HIV-2 in adults and children across sample types. The assay could help avert transmission during acute HIV, simplify HIV diagnostic algorithms, and promote the survival of HIV-infected children.

A Longitudinal Seroprevalence Study Evaluating Infection Control and Prevention Strategies at a Large Tertiary Care Center with Low COVID-19 Incidence

Personal protective equipment and adherence to disinfection protocols are essential to prevent nosocomial severe acute respiratory syndrome coronavirus (SARS-CoV-2) transmission. Here, we evaluated infection control measures in a prospective longitudinal single-center study at the Vienna General Hospital, the biggest tertiary care center in Austria, with a structurally planned low SARS-CoV-2 exposure. SARS-CoV-2-specific antibodies were assessed by Abbott ARCHITECT chemiluminescent assay (CLIA) in 599 health care workers (HCWs) at the start of the SARS-CoV-2 epidemic in early April and two months later. Neutralization assay confirmed CLIA-positive samples. A structured questionnaire was completed at both visits assessing demographic parameters, family situation, travel history, occupational coronavirus disease 2019 (COVID-19) exposure, and personal protective equipment handling. At the first visit, 6 of 599 participants (1%) tested positive for SARS-CoV-2-specific antibodies. The seroprevalence increased to 1.5% (8/553) at the second visit and did not differ depending on the working environment. Unprotected SARS-CoV-2 exposure (p = 0.003), positively tested family members (p = 0.04), and travel history (p = 0.09) were more frequently reported by positively tested HCWs. Odds for COVID-19 related symptoms were highest for congestion or runny nose (p = 0.002) and altered taste or smell (p < 0.001). In conclusion, prevention strategies proved feasible in reducing the risk of transmission of SARS-CoV-2 from patients and among HCWs in a low incidence hospital, not exceeding the one described in the general population.

SUBCLINICAL VASCULAR DAMAGE IN PATIENTS WITH SEVERE DYSLIPIDEMIA DEPENDING ON BLOOD PRESSURE LEVELS: 5-YEAR FOLLOW-UP RESULTS

Objective: The aim of the present study was to estimate the 5-year dynamics of vascular subclinical parameters in patients with severe dyslipidemia depending on blood pressure levels. Design and method: 1600 apparently healthy Saint-Petersburg inhabitants aged 25–65 years were randomly selected (sample from ESSE-RF national epidemiology survey) in 2013. All participants signed informed consent and filled in the questionnaire regarding risk factors, concomitant diseases and therapy. 134 patients with severe dyslipidemia (LDL-C&gt;4,9 mmol/l, or medication prescribed for dyslipidemia) were selected and invited for follow-up visit in 2018. Fasting lipids, glucose (Abbott Architect 8000) and vital signs were obtained. Cardio-ankle vascular index (CAVI) and ankle brachial index (ABI) were measured by VaSera VS-1500 (Fukuda). Measurement of intima-media thickness (IMT) was performed by My Sono U6 (Samsung). Statistical analysis was performed using SPSS Statistics 20. Results: Among 134 patients 45 were male and 89 - female. Only 46 patients (34.3%) were taking statins. There was a significant difference in mean levels of SBP/DBP at the visits 1 and 2 (132.25 ± 17.22/80.92 ± 9.34 and 133.98 ± 20.06/81.02 ± 11.62 mm Hg respectively, p &lt; 0.001 for both), creatinine (67.82 ± 10.34 and 70.86 ± 11.94 mmol/l, p &lt; 0.001) and lipid profile dynamics (TC – 6.93 ± 1.44 and 6.41 ± 1.46 mmol/l respectively, p &lt; 0.001; LDL-C – 4.81 ± 1.27 and 4.29 ± 1.31 mmol/l respectively, p &lt; 0.001). Table 1. Prevalence of subclinical vascular damage - 5-year observation. Conclusions: Prevalence of statin intake is still not high, even among patients with severe dyslipidemias. 5-year observation demonstrates more rapidly progressing artheriosclerosis according to CAVI in hypertensive patients. CAVI could be tested in further studies as the instrument of cumulative BP control being a marker of exposure of high BP levels.

High-sensitivity cardiac troponin I: is ethnicity relevant?

AimsTo evaluate 99th percentile upper reference limits (URLs) and investigate ethnic differences for the Abbott Architect high-sensitivity cardiac troponin I (hs-cTnI) in a middle-aged to elderly cosmopolitan population.MethodsIn subjects without...

Time-related performance characteristics of high-sensitivity troponin I assay using manufacturer’s controls and reagents

BackgroundTroponin is a widely used cardiac protein biomarker for acute coronary syndrome. Its increasing importance drives an increasing need to assess, in real-world conditions, the performance of the tests to measure it. We evaluated the performance characteristics of high-sensitivity troponin I assay reagents and ancillary agents on the Abbott ARCHITECT ci4100, ARCHITECT i2000SR and Alinity ci using historical quality control data spanning 5 years. Design and methodRetrospective diagnostic hs-TnI quality control data were collected between 2015 and 2019 from the Abbott ARCHITECT ci4100, ARCHITECT i2000SR and Alinity ci located in the University College Dublin Clinical Research Centre Core Lab facility. Descriptive statistics for bias and variability were generated. Linear regression models were used to calculate the mean hs-TnI concentrations over Abbott quality control or reagent lot age and over time from the last calibration of the analysers. ResultsMeasurement bias on all three systems ranged between -2.49% and 3.98%. The total CV was ≤8.80%, with a within-lot variability for the reagents and controls of ≤5.45% and ≤7.13%, respectively. The between-lot CVs for reagents and controls were ≤7.16% and 6.19%, respectively. The effect of control or reagent age did not greatly affect stability over time. Results were also stable over different times from the last calibration of the analysers. ConclusionThe results of this study show that the Abbott hs-TnI assay on the ARCHITECT i2000sr and ARCHITECT ci4000 systems is quite stable in a core laboratory environment. The Alinity ci system exhibits similar performance characteristics.

Independent and combined effects of biotin and hemolysis on high-sensitivity cardiac troponin assays.

This study compared the independent and combined effects of hemolysis and biotin on cardiac troponin measurements across nine high-sensitivity cardiac troponin (hs-cTn) assays. Parallel cTn measurements were made in pooled lithium heparin plasma spiked with hemolysate and/or biotin using nine hs-cTn assays: Abbott Alinity, Abbott ARCHITECT i2000, Beckman Access 2, Ortho VITROS XT 7600, Siemens Atellica, Siemens Centaur, Siemens Dimension EXL cTnI, and two Roche Cobas e 411 Elecsys Troponin T-hs cTnT assays (outside US versions, with and without increased biotin tolerance). Absolute and percent cTn recovery relative to two baseline concentrations were determined in spiked samples and compared to manufacturer's claims. All assays except the Ortho VITROS XT 7600 showed hemolysis and biotin interference thresholds equivalent to or greater than manufacturer's claims. While imprecision confounded analysis of Ortho VITROS XT 7600 data, evidence of biotin interference was lacking. Increasing biotin concentration led to decreasing cTn recovery in three assays, specifically both Roche Cobas e 411 Elecsys Troponin T-hs assays and the Siemens Dimension EXL. While one of the Roche assays was the most susceptible to biotin among the nine studied, a new version showed reduced biotin interference by approximately 100-fold compared to its predecessor. Increasing hemolysis also generally led to decreasing cTn recovery for susceptible assays, specifically the Beckman Access 2, Ortho VITROS XT 7600, and both Roche Cobas e 411 Elecsys assays. Equivalent biotin and hemolysis interference thresholds were observed at the two cTn concentrations considered for all but two assays (Beckman Access 2 and Ortho VITROS XT 7600). When biotin and hemolysis were present in combination, biotin interference thresholds decreased with increasing hemolysis for two susceptible assays (Roche Cobas e 411 Elecsys and Siemens Dimension EXL). Both Roche Cobas e 411 Elecsys as well as Ortho VITROS XT assays were susceptible to interference from in vitro hemolysis at levels routinely encountered in clinical laboratory samples (0-3g/L free hemoglobin), leading to falsely low cTn recovery up to 3ng/L or 13%. While most assays are not susceptible to biotin at levels expected with over-the-counter supplementation, severely reduced cTn recovery is possible at biotin levels of 10-2000ng/mL (41-8,180nmol/L) for some assays. Due to potential additive effects, analytical interferences should not be considered in isolation.

Prevalence of Detectable Biotin in Five US Emergency Department Patient Cohorts

BackgroundThe objective of this study was to estimate the prevalence of biotin supplementation in United States emergency department patients using a multi-site, geographically distributed sampling model. MethodsBiotin was measured using an Abbott ARCHITECT Biotin research use only assay in 7118 emergency department patient serum or plasma samples from five US medical centers. Samples with biotin ≥10 ng/mL underwent additional LC-MS/MS confirmatory testing for biotin and its primary metabolites. The overall and site-specific prevalence of detectable biotin was determined using the screening assay while biotin speciation (i.e., prevalence of detectable metabolites) was determined using LC-MS/MS. ResultsOf 7118 samples screened, 291 (4.1%) had biotin ≥10 ng/mL and were considered positive. Across five medical centers, the fraction of positive samples ranged from 2.0% to 5.4%. The maximum biotin concentration observed was 355 ng/mL. Of the 285 positive screens that underwent additional LC-MS/MS testing, 89 (31%) showed detectable biotin, bisnorbiotin, and/or biotin sulfoxide. Biotin, bisnorbiotin, and biotinsulfoxide were detected in 82/89 (92.1%), 61/89 (68.5%), and 18/89 (20.2%) samples, respectively; biotin was detected in the absence of either metabolite in 18/89 (20.2%) samples. ConclusionsUsing a screening assay, 4.1% of emergency department patient samples were found to be potentially susceptible to interference from biotin. Confirmatory testing showed detectable biotin and/or biotin metabolites in 31% of positive screens (1.3% overall). The prevalence of biotin ≥10 ng/mL varied 2–3-fold across US emergency department patient cohorts. Biotin metabolites were observed in 80% of samples confirmed to have detectable biotin species by LC-MS/MS, suggesting that rigorous assessments of assay susceptibility to biotin interference, often performed using in vitro studies, should consider the potential role of biotin metabolites present in vivo.

Viral suppression is associated with HIV-antibody level and HIV-1 DNA detectability in early treated children at 2 years of age.

Early infant HIV diagnosis and antiretroviral therapy (ART) initiation are now implemented shortly after birth. Maintaining and monitoring ART adherence is difficult and requires frequent visits. We, therefore, investigated whether HIV antibodies and HIV-1 DNA levels are markers of cumulative viremia. We conducted a cross sectional investigation at 2 years of age of HIV antibodies and HIV-1 DNA levels in a well characterized cohort of 31 children who started ART shortly after birth. HIV antibodies were measured by a combination of the Abbott ARCHITECT HIV Ag/Ab Combo and Geenius HIV 1/2 supplemental assays; and total HIV-1 DNA quantified using a sensitive quantitative PCR (qPCR) assay targeting the HIV-1 integrase gene. Infant post-exposure prophylaxis consisted of zidovudine (AZT) and nevirapine (NPV) (or NVP only, in one child) within 1 day of birth, transitioning, after positive diagnosis, to three-drug ART, at a median [interquartile range (IQR)] of 7 (4-9.5) days. Twelve of 31 children had well suppressed HIV plasma viral loads (HIVVL) and the remainder periods of viremia (HIVVL > 100 copies/ml after 3 months of ART), classified as non-suppressed. At 24 months of age: 11 of 12 (92%) of well suppressed children had undetectable HIV-1 antibodies versus 3 of 19 (16%) non-suppressed children (P < 0.001) and 7 of 12 (58%) well suppressed children had undetectable HIV-1 DNA versus 3 of 19 (16%) non-suppressed children (P = 0.02). Considering low assay costs and the high proportion of well suppressed children with undetected antibody levels at 2 years, HIV antibody levels may be a valuable marker of cumulative adherence in children who start treatment shortly after birth and could prompt adherence and viral load investigation.