Roche Elecsys Research Articles

The Androstenedione Roche Elecsys immunoassay has superior comparability to the LC-MS/MS assay than the Siemens Immulite immunoassay

Androstenedione (ASD) is a biomarker used in the diagnostic workup of hyperandrogenism, congenital adrenal hyperplasia, premature adrenarche, and polycystic ovary syndrome (PCOS). The Elecsys ASD competitive electrochemiluminescence immunoassay (Roche Diagnostics, Indianapolis, IN) is a new assay recently available in the US. ObjectiveThis study evaluated the analytical and clinical performance of the Elecsys ASD assay. Design & MethodsWe evaluated the linearity/analytical measuring range (AMR), precision, and accuracy of the Elecsys ASD assay on the cobas e601 analyzer. ASD was measured in serum/plasma in the Elecsys ASD, Immulite (Siemens Medical Solutions USA, Inc. Malvern, PA), and LC-MS/MS assays. Reference intervals (RI) were evaluated across genders, menopausal status, and in children. Statistical analysis was performed using EP evaluator and R program. ResultsThe Elecsys ASD assay had a linear response across the AMR. The intra- and inter-assay coefficients of variation at various concentrations were ≤4.5%. The Elecsys ASD assay had a mean difference of −0.04 ng/mL (−1.7%) with the LC-MS/MS assay, whereas the Immulite assay had a mean difference of 1.17 ng/mL (66%) and −1.22 ng/mL (−38%) compared to the LC-MS/MS and Elecsys ASD assays, respectively. The Roche recommended RIs for healthy men (0.280–1.52 ng/mL) and postmenopausal women (0.187–1.07 ng/mL) were successfully verified. The RIs for children were adopted from published data. For pre-menopausal women, a RI of <1.60 ng/mL was established. The ASD concentrations in women with and without PCOS overlapped. ConclusionsThe Elecsys ASD assay has superior comparability to the LC-MS/MS assay than the Immulite assay.

Severe acute respiratory syndrome coronavirus 2 antibody response to a third dose of homologous messenger RNA vaccination in liver transplantation recipients.

Severe acute respiratory syndrome coronavirus 2 antibody response to a third dose of homologous messenger RNA vaccination in liver transplantation recipients.

Using sero-epidemiology to monitor disparities in vaccination and infection with SARS-CoV-2

As SARS-CoV-2 continues to spread and vaccines are rolled-out, the “double burden” of disparities in exposure and vaccination intersect to determine patterns of infection, immunity, and mortality. Serology provides a unique opportunity to measure prior infection and vaccination simultaneously. Leveraging algorithmically-selected residual sera from two hospital networks in the city of San Francisco, cross-sectional samples from 1,014 individuals from February 4–17, 2021 were each tested on two assays (Ortho Clinical Diagnostics VITROS Anti-SARS-CoV-2 and Roche Elecsys Anti-SARS-CoV-2), capturing the first year of the epidemic and early roll-out of vaccination. We estimated, using Bayesian estimation of infection and vaccination, that infection risk of Hispanic/Latinx residents was five times greater than of White residents aged 18–64 (95% Credible Interval (CrI): 3.2–10.3), and that White residents over 65 were twice as likely to be vaccinated as Black/African American residents (95% CrI: 1.1–4.6). We found that socioeconomically-deprived zipcodes had higher infection probabilities and lower vaccination coverage than wealthier zipcodes. While vaccination has created a ‘light at the end of the tunnel’ for this pandemic, ongoing challenges in achieving and maintaining equity must also be considered.

MO186: Third COVID-19 Vaccine Dose Maximizes Antibody Titer in Kidney Transplant Recipients

BACKGROUND AND AIMSCOVID-19 infection in solid organ transplant recipients (SOT) is associated with increased morbidity and mortality due to comorbidities and immunosuppression state (Chaudhry ZS et al, 2020). Although vaccines represent the greatest hope to control COVID-19 pandemic, several studies showed the low immunogenicity of a two-dose mRNA COVID-19 vaccine regimen in SOT as compared with general population (Boyarsky BJ et al, 2021). Based on this evidence, on September 2021, the Italian Medicine Agency (AIFA) authorized a third vaccine administration as additional primary dose to immunocompromised patients.The aim of this study is to evaluate the seroconversion rate after the third dose of BNT162b2 (Pfizer-BioNTech) SARS-CoV-2 mRNA vaccine in kidney transplant recipients (KTRs) and to investigate the baseline factors associated with the absence of the antibody response.METHODwe performed a prospective and observational study on a monocentric cohort of 329 consecutive Caucasian KTRs given three doses of the BNT162b2 COVID-19 vaccine. Key exclusion criteria were a previous history of COVID-19 infection and transplantation or having underwent chemotherapy treatment within the last year. Antibody response against the spike protein was tested on blood sample collected before the administration of vaccine (T0), at 15 and 90 days after the second dose (T2 and T3, respectively) and one month after the third dose (T5). The level of antibodies was assessed using the Roche Elecsys anti–SARS-CoV-2 S enzyme immunoassay (positive cut-off ≥ 0.8 U/mL). A total of 22 patients were excluded from the analysis because categorized as SARS-CoV-2-pre-immunized according to the antibodies’ baseline status (T0) above the positivity cut-off.The Local Ethics Committees approved the study protocol and written informed consent was obtained before enrolment.RESULTSThe study population of 307 KTRs was 57.10 ± 13.10 years, with a predominance of male sex (64.2%). Median time from transplantation to vaccine was 10 [IQR 5–17] years. Blood analysis at baseline revealed mean eGFR assessed by Chronic Kidney Disease Epidemiology Collaboration (CKD-EPI) equation to be 56.95 ± 23.04 mL/min/1.73 m2.The standard immunosuppressive regimen consisted of glucocorticoids in all patients, calcineurin inhibitors (88.6% of patients), antimetabolites (73.3% of patients) and mTOR inhibitors (in 15.6% of patients). The first two doses were administered 21 days apart, and the third dose was administrated 172 ± 4 days after the second dose.In our cohort, 43.3% patients (133/307) responded to the vaccine at T2. The proportion of responders increased to 68.4% (186/272) at T3 (median antibody level: 5.2 [0.40–74.07]). One month after the third dose, a positive antibody titer was detected in 251 of 307 patients (81.8%) (median antibody titre: 1137.50 [9.32–4189.75]). The response curve starting at T2 and increasing at T3 makes apparent that there is a distinctive kinetic of humoral response in immunocompromised patients compared to immunocompetent individuals (Walsh EE et al., 2020). A multivariate analysis showed that the negative response to the third primary dose was associated with antimetabolite immunosuppressants (P = .001), lower estimated glomerular filtration rate (P < .001) and female sex (P = .04) (Figure 1). No serious adverse events were reported. Neither denovo DSAs nor change in proteinuria were reported after vaccination.FIGURE 1:Univariate and multivariate analysis of factors associated with vaccine response one month after third dose of SARS-CoV-2 mRNA vaccine.The limitation of this study is the absence of assays for cellular immune response.CONCLUSIONAlthough the exact threshold of antibody titer for protection against SARS-CoV-2 infection remains unclear, the ability of the additional mRNA COVID-19 vaccine dose to increase both immune response (Figure 2A) and the prevalence of seroconversion rate (Figure 2B) associated with the acceptable safety profile supports its use after an initial 2-dose mRNA COVID-19 primary vaccine series in immunocompromised patients.FIGURE 2:Antibody Response. Panel A shows the anti-SARS-CoV-2 antibody titers at different timepoints T0, T2, T3 and T5. Panel B shows prevalence of responders and noresponders at different timepoints T0, T2, T3 and T5.

Unstable angina in the context of high sensitive troponins: still a marker of high risk? A comparison of outcomes with adjudicated type 1 myocardial infarction

Abstract Funding Acknowledgements Type of funding sources: None. Background Unstable angina (UA), considered historically a marker of high risk, has rarely been studied in the high sensitive troponin era. We sought to characterise this population and determine short and medium term outcomes for UA who did not have elevated high sensitive troponins and compared this to adjudicated type 1 MI and the global population of suspected ACS. Method We conducted a post-hoc analysis of 2 prospective cohort studies of suspected acute coronary syndrome in 2 hospitals in the northwest of England. (n=3018) We used a symptom scoring system to diagnose unstable angina. Type 1 MI was diagnosed by blinded, independent physician adjudication according to 3rd universal criteria for MI. Follow-up was 100% complete for all patients to 1 year. Results 185 and 259 were adjudicated as suffering from UA and NSTEMI respectively. We restricted our analysis to 158 patients with UA with high sensitive troponin T (Roche elecsys) ≤14ng/l (≤99th percentile). Compared to NSTEMI population UA cohort were younger (59 vs 74, p&amp;lt;0.002), had a lower incidence of hypertension (56% vs 69%, p= 0.009), had lower risk scores (TIMI 2 vs 3, p=0.001, GRACE 97.5 vs 140, p&amp;lt;0.0001, HEART 4 vs 7, p&amp;lt;0.0001) and had lesser ECG abnormalities ( ST depression &amp;gt;1mm, 5% vs 15.6%, p=0.001, T wave flattened, biphasic or inverted 24% vs 47.8%, p&amp;lt;0.0001). Type 1 MI to 30 days and 1 year in the UA cohort was 1.9% and 3.1% respectively compared to a repeat type 1 MI in the NSTEMI cohort of 0.8% and 2.4% respectively. Only 1 (0.8%) all cause death was recorded within one year in the unstable angina cohort as opposed to 36 (14.4%) in the NSTEMI group. Revascularisation rates were unsurprisingly lower in the UA cohort to 30 days compared to NSTEMI cohort (table 1) Conclusion Unstable angina, in the high sensitive troponin era is associated with a small early and medium term risk of myocardial infarction. Risk of medium-term MACE is much lower compared to patients with confirmed type 1 myocardial infarction.

Detection of antibodies against SARS-CoV-2 both in plasma pools for fractionation and in commercial intravenous immunoglobulins produced from plasma collected in Italy during the pandemic.

We investigated the presence of anti-SARS-CoV-2 antibodies in Italian plasma pools and intravenous immunoglobulins sent to our Institute (Italian National Institute of Health - Istituto Superiore di Sanità) in the context of the Official Control Authority Batch Release. The plasma pools were made up from donations collected in several different Italian regions from May 2017 to October 2020, i.e. in the pre-pandemic and pandemic periods. All plasma pools were initially tested for the qualitative detection of anti-SARS-CoV-2 antibodies against the nucleocapsid protein using the Roche Elecsys® Anti-SARS-CoV-2 test kit. Plasma pools positive for these antibodies were further tested using the Roche Elecsys® Anti-SARS-CoV-2 S test kit for the quantitative detection of antibodies against SARS-CoV-2 spike receptor binding domain. All plasma pools showing reactivity to these antibodies were tested undiluted for the presence of SARS-CoV-2 RNA using the Grifols Procleix SARS-CoV-2 transcription-mediated amplification assay. Intravenous immunoglobulins were tested using both test kits to determine the presence of anti-SARS-CoV-2 antibodies. All plasma pools made up from donations collected in the pre-pandemic period were negative for anti-SARS-CoV-2 antibodies against the nucleocapsid protein. Of the plasma pools made up from donations collected from December 2018 to March 2020, only 1 pool out of 68 (1.4%), that was made up from donations from the Lombardy region, was reactive for these antibodies. Interestingly, 105 out of 174 (60.3%) of the plasma pools made up from donations collected from November 2018 to October 2020 showed the presence of these antibodies. All plasma pools positive for these antibodies were tested for antibodies against SARS-CoV-2 spike receptor binding domain and were confirmed positive. None of these plasma pools tested were reactive for SARS-CoV-2 RNA. In the case of intravenous immunoglobulins, 20 out of 25 (80%) batches showed the presence of both anti-SARS-CoV-2 antibodies, reflecting the concentration in the plasma pools used for their production.

New Diagnostic Cutoffs for Adrenal Insufficiency After Cosyntropin Stimulation Using Abbott Architect Cortisol Immunoassay

IntroductionThe accurate interpretation of the cosyntropin (adrenocorticotropic hormone [ACTH]) stimulation test requires method- and assay-specific cutoffs of the level of cortisol. Compared with a historical cutoff (18 μg/dL) for polyclonal antibody-based immunoassays, lower thresholds were proposed for the Roche Elecsys II assay, which uses a monoclonal antibody. However, cutoffs for other commonly adopted, monoclonal antibody-based cortisol assays were not yet available. Here, we established the thresholds for the level of cortisol specific to the Abbott Architect immunoassay by comparing the measurements of the level of cortisol using 3 immunoassays. MethodsThe ACTH stimulation test was performed in patients with suspected adrenal insufficiency (n = 50). The serum cortisol level was measured using the Abbott Architect, Roche Elecsys II, and Siemens Centaur assays. The results of the Abbott assay were also compared with those of liquid chromatography-tandem mass spectrometry. The receiver operating characteristic analysis was performed to derive new diagnostic thresholds for the Abbott assay using the polyclonal antibody-based Siemens assay as the reference method. ResultsThe concentrations of cortisol measured using the Abbott assay were similar to those measured using liquid chromatography-tandem mass spectrometry and the Roche Elecsys II assay but significantly lower than those measured using the Siemens assay. The optimized threshold for cortisol using the Abbott assay was 14.6 μg/dL at 60 minutes after stimulation (sensitivity, 92%; specificity, 96%) and 13.2 μg/dL at 30 minutes after stimulation (sensitivity, 100%; specificity, 89%). ConclusionWe recommend a threshold of 14.6 μg/dL for the level of cortisol at 60 minutes after ACTH stimulation for the Abbott assay. In comparison with the historical threshold of 18 μg/dL, the application of the new cutoff may significantly decrease false-positive results due to ACTH stimulation testing. The use of assay-specific cutoffs will be essential for reducing misclassification and overtreatment in patients with suspected adrenal insufficiency.

Frequency histograms of three high-sensitivity cardiac troponin assays in a reference population.

BackgroundCardiac troponin (cTn) values above the 99th percentile upper reference limit (URL) indicate myocardial injury. We established 99th percentile URLs for three high‐sensitivity cTn (hs‐cTn) assays (Beckman Coulter Access hs‐cTnI, Abbott STAT hs‐cTnI, and Roche Elecsys hs‐cTnT) using a healthy population in Korea.MethodsEach cTn value was measured by three assays and analyzed by dividing by gender and age.ResultsThe frequency histograms of log‐transformed cTn values for Beckman and Abbott assays exhibited a bell‐shaped distribution. The 99th percentile URLs were 9.8, 17.4, and 17.3 ng/L in the total population; 10.9/9.0, 18.9/17.0, and 18.9/17.7 ng/L in the male/female population (p < 0.001 for all three assays); and 11.2/7.2, 19.9/14.5, and 22.7/9.3 ng/L in the older/younger population (p < 0.001 for all three assays) for Beckman, Abbott, and Roche assays, respectively.ConclusionAmong the three assays, bell‐shaped distributions were observed in a frequency histogram of log‐transformed cTn values for healthy population in Beckman and Abbott assays. Also, our findings show that the 99th percentile URLs for cTn levels vary not only by gender but age.

The role and diagnostic accuracy of serology for COVID-19

BackgroundThe role and performance of various serological tests for the diagnosis of COVID-19 are unclear. This study aimed to evaluate the performance of seven commercially available serological assays for SARS-CoV-2 antibodies by testing COVID-19 cases and controls.MethodsAdult patients with fever for > 5 days, admitted to a tertiary-care teaching hospital in South India, were enrolled prospectively between June and December 2020. SARS-CoV-2 RT-PCR confirmed patients were classified as cases, and patients with febrile illness with laboratory-confirmed alternative diagnosis and healthy participants were controls. All participants were tested with SCoV-2 Detect™ IgM ELISA kit and SCoV-2 Detect™ IgG ELISA kit (InBios International, Seattle, USA) (Inbios), SARS-CoV-2 Total and SARS-CoV-2 IgG (Siemens Healthcare Diagnostics Inc., Tarrytown, USA) (Siemens), Roche Elecsys® Anti-SARS-CoV-2 (Roche Diagnostics, Rotkreuz, Switzerland) (Roche), Abbott SARS-CoV-2 IgG (Abbott Diagnostics, IL, USA) (Abbott), and Liaison® SARS-CoV-2 S1/S2 IgG (DiaSorinS.p.A., Saluggia, Italy) (Liaison). The sensitivities, specificities, positive predictive values (PPV), negative predictive values (NPV), and accuracies were compared.ResultsThere were 303 participants: 153 cases and 150 controls. ELISA detecting anti-S protein antibody was more sensitive (88.9% for IgG and 86.3% for IgM) than the CLIAs (82.4% for total antibodies and 76.5–85.6% for IgG). Among CLIAs, Roche IgG was most sensitive (85.6%) followed by Abbott (83%) and Liaison (83%). Abbot had the best PPV (88.8%) and was more specific (89.3%) than Liaison (82%) and Roche (82%). Siemens IgG was less sensitive (76.5%) than Siemens Total (82.4%). The specificity of all the serological assays was modest (75–90%). Antibody test positivity increased with the duration of illness reaching 90% after 10 days of illness. When cases were compared against pre-pandemic controls, the IgG gave excellent specificity (98–100%). For seroprevalence studies, InBios IgG had the best accuracy (90.8%) with 88.9% sensitivity and 97.6% specificity.ConclusionThe serological assays are important adjuncts for the diagnosis of COVID-19 in patients with persistent symptoms, especially in the second week of illness. The value of serological diagnostic tests is limited in the first week of illness and they provide additional value in seroprevalence studies. The diagnostic accuracy of the ELISA and CLIA platforms were comparable.

Antibody response to mRNA SARS-CoV-2 vaccination in 182 patients after allogeneic hematopoietic cell transplantation.

IntroductionPatients after allogeneic stem cell transplantation are at high risk for infection‐related complications, and vaccination efficacy might be impaired depending on the immune reconstitution. In this study, we evaluate their response to mRNA vaccines against SARS‐CoV‐2.MethodsDuring routine follow‐up visits, patients were asked about their vaccination status and if they had a previous infection with SARS‐CoV‐2. In fully vaccinated patients, the antibody titer was measured using the Roche Elecsys Anti‐SARS‐CoV‐2 S test. A titer of <1 U/L was considered as negative, titers of ≥250 U/ml as a high antibody titer, and a titer of 50–249 U/ml as a low antibody titer. Patient characteristics were evaluated by chart review to identify risk factors for poor vaccination response.ResultsThe majority of patients developed a high antibody titer (138 out 182 patients, 75.8%). Risk factors for a low antibody titer were immunosuppressive therapy, a lymphocyte count <0.9 G/L, ongoing treatment for the underlying malignancy, and active graft‐versus‐host disease (GvHD). Donor type, underlying disease, a previous SARS‐CoV‐2 infection, and sex did not significantly influence the response to the vaccination.DiscussionWhile patients undergoing allogeneic stem cell transplantation have been excluded from the initial registration trials, our real‐world experience with a large patient cohort confirms the data of previous studies, showing that most patients do have a good response to mRNA vaccines against SARS‐CoV‐2. Nevertheless, a significant proportion of patients shows an inadequate vaccination, which can be improved after a third vaccination in most cases despite immunosuppressive therapy.

Antibody Responses to COVID-19 Vaccination in Left Ventricular Assist Devices

PurposeLeft ventricular assist device (LVAD) implantation is associated with immune dysregulation and common occurrence of major infections. Whether humoral responses to COVID-19 vaccination are protective and durable in LVAD patients is uncertain.MethodsWe conducted a prospective single-center cohort study in LVAD patients without prior COVID-19 infection, who received 2 doses of BNT162b2 (Pfizer) or mRNA-1273 (Moderna) or 1 dose of Ad26.COV2.S (J&J) COVID-19 vaccines. Serologic testing was performed at 3, 6, and 9 months after COVID-19 vaccination using the Roche Elecsys anti-SARS-CoV-2 spike enzyme immunoassay (range <0.4 to >2500 U/mL [positive ≥0.8]), which tests for antibodies against the spike protein's receptor-binding domain (RBD).ResultsIn March 2021, 45 LVAD patients (80% HeartMate 3) were enrolled and 24 (53%) received Pfizer vaccines, 17 (38%) Moderna, and 4 (9%) J&J at a median duration of LVAD support of 34 months (1-114). Most were male (89%) and white non-Hispanic (71%) persons with median age 62 years (23-78); 26 (58%) had diabetes, 16 (36%) had chronic kidney disease (CKD), and 3 (7%) were on immunosuppressive medications. Median absolute lymphocyte count (ALC) at the time of their vaccine was 1.26 K/uL (0.54-3.41). All patients developed a detectable anti-RBD antibody after vaccination, which began to wane after 3 months. The median anti-RBD IgG titers were 1132 U/mL, 360 U/mL, and 286 U/mL at 3, 6, and 9 months, respectively, post-vaccination (Figure). Age > 60 years, ALC < 1.5 K/uL, and history of CKD were associated with lower median anti-RBD IgG titers at 3, 6, and 9 months. Moderna vaccine recipients had the highest and J&J the lowest anti-RBD IgG titers at 3-months. In the 9-month study period, there were no vaccine-related serious adverse events or breakthrough COVID-19 infections.ConclusionLVAD patients exhibit a robust humoral response to COVID-19 vaccination without breakthrough infection. Further research to evaluate cellular responses to COVID-19 vaccination in LVAD patients is warranted.

412 Cortisol cut off point to diagnose adrenal insufficiency (AI) using a monoclonal antibody immunoassay

OBJECTIVES/GOALS: AI is diagnosed when peak cortisol level after a cosyntropin stimulation test is &lt;18 mg/dL using polyclonal antibody (pAb) immunoassay. However, the polyclonal assay is being replaced by a specific monoclonal antibody (mAb) immunoassay which yields lower cortisol levels, leading to the over diagnosis of AI and use of unnecessary steroid use. METHODS/STUDY POPULATION: We obtained 36 samples from patients undergoing 1 mcg cosyntropin stimulation tests for diagnosis of AI. Samples were analyzed using pAb immunoassay (Abbott Architect Cortisol), mAb immunoassay (Roche Elecsys Cortisol II), and mass spectrometry (MS). AI was diagnosed if serum cortisol level was &lt;18 using the pAb immunoassay. Measurements by MS and mAb immunoassay were individually used in simple logistic regression models to predict AI. For each model, we calculated a cortisol level corresponding to a 50% probability (median) of AI and used the delta method to determine the standard error and 95% confidence interval of the median. We used receiver operator characteristic (ROC) curve, area under the curve, sensitivity, and specificity to evaluate the potential of the median values as thresholds for each predictor. RESULTS/ANTICIPATED RESULTS: Data showed a mean cortisol level of 17 mcg/dL using the pAb immunoassay, 12 mcg/dL using the mAb immunoassay, and 12.96 mcg/dL using MS. The mean difference in cortisol level between the mAb immunoassay and the pAb immunoassay was 5.12 mcg/dL (p-value &lt;0.01). The ROC curve model indicated an area under the curve of 0.997 with a median value of 11.2 mcg/dL for the mAb immunoassay. This provides a sensitivity of 95%, specificity of 95%, positive predictive value of 95%, and negative predictive value of 94%. This new threshold has a Kappa coefficient of 0.89 when compared to the pAb immunoassay. DISCUSSION/SIGNIFICANCE: New and highly specific mAb immunoassays are being used more widely but yield lower cortisol results. This reflects the need for further studies to determine new cut off points for highly specific cortisol immunoassays. A cut off level of 11.2 mcg/dL would provide a sensitivity of 95% and specificity of 95%.

Factors associated with poor antibody response to third-dose SARS-CoV-2 vaccination in patients with rheumatic and musculoskeletal diseases.

Factors associated with poor antibody response to third-dose SARS-CoV-2 vaccination in patients with rheumatic and musculoskeletal diseases.

Age-specific reference values for the 5th generation cardiac troponin T assay in Chinese children.

The clinical use of the cardiac troponin T (cTnT) assay was limited to the adult population in the diagnosis and prognosis of myocardial injury. However, emerging studies indicated its significant value in the assessment of pediatric cardiology, and it has been routinely measured in most hospitals. Our study investigated the normative values of cTnT in Chinese children and reported the age-specific 99th percentile cut-off for them.A total of 1280 apparently healthy Chinese children were enrolled in our study. Serum levels of cTnT were analyzed on the Roche Elecsys Troponin T Gen 5 STAT assay. According to the Clinical and Laboratory Standards Institute C28-A3 guideline, the 99th percentile upper reference limits (URLs) with 90% confidence intervals (CIs) were calculated in different age subgroups.The 99th percentile URL was 38 (90%CI: 37.0-51.0) ng/L for 1 to <4months old, 26 (90%CI: 25.2-28.5) ng/L for 4 to ≤ 12months old, and 12 (90%CI: 11.1-12.9) ng/L for 1 to 18 years old, respectively. For subjects aged from 1 to 18years, boys had slightly higher cTnT levels than girls (P = .003), while our assay could not measure low cTnT concentrations (≥the limit of detection) in 50% girls.Our study provided age-specific URLs of cTnT for Chinese children, with the 5th generation cTnT assay from Roche Diagnostics. It had significant clinical implications in the interpretation and use of test results for pediatric cardiology.

Seroprevalence of COVID-19 infection among vaccine naïve population after the second surge (June 2020) in a rural district of South India: A community-based cross-sectional study.

To determine the seroprevalence of the SARS Cov 2 infection among vaccine naive population in a rural district of South India post-second surge. We conducted a cross-sectional study in the five villages of a randomly chosen sub-district in the Bangalore rural district. We did house to house surveys and recruited 831 vaccine naive adults in July 2021. We tested samples for the presence of antibodies (including IgG & IgM) to SARS CoV-2 using the Roche Elecsys SARS-CoV-2 -S assay that quantifies antibodies against the receptor-binding domain (RBD) of the spike (S) protein. We estimated an overall prevalence of 62.7% (95% CI: 59.3-66.0) and an age-and gender-adjusted seroprevalence of 44.9% (95% CI: 42.5-47.4). When adjusted for test performance, the seroprevalence was 74.64% (95% CI: 70.66-78.47). The case-to-undetected-infected ratio (CIR) was 1: 8.65 (95% CI 1:8.1-1:9.1), and the Infection Fatality Rate (IFR) was 16.27 per 100,00 infections as of 13 July 2021. A history of at least one symptom suggestive of COVID-19 or a positive COVID-19 test of self or a family member in the past were significantly associated with seropositivity. We report a high seroprevalence of COVID-19 infection despite the advantages of low population density and well-ventilated landscapes in rural areas. CIR and IFR were higher than the previous serosurvey conducted in the same population during the first surge. The thought of achieving herd immunity comes with relief. However, it's vital to put efforts into building population health and rural health infrastructure to avert future health catastrophes.

Short Research Communication Anti-Spike Antibody Response to COVISHIELD™ (SII-ChAdOx1 nCoV-19) Vaccine in Patients with B-Cell and Plasma Cell Malignancies and Hematopoietic Cell Transplantation Recipients.

IntroductionThere is limited data on the serologic antibody responses after the ChAdOx1 vaccine in patients with hematological malignancies and hematopoietic cell transplantation recipients. There is no data on the safety and efficacy of the Indian COVISHIELD™ vaccine in this population.MethodsThis study reports the anti-S antibody response to the COVISHIELD™ vaccine in a prospective cohort of patients with B-cell and plasma cell malignancies and HCT recipients at a single center. The quantitative antibodies to the SARS-CoV-2 S protein receptor-binding domain in human plasma were determined by the validated Roche Elecsys Anti-SARS-CoV-2 S kit.ResultsA total of 118 patients were included over the study period from April 2021 to August 2021. The seropositivity rate at baseline and after the first and second dose of the vaccine was 39%, 66%, and 79%, respectively (p < 0.0001). The seronegative cohort had a higher median age (65 vs. 60 years, p = 0.03), were more likely to be males (81% vs. 42%, p = 0.009), had a diagnosis of B-CLPD (100% vs. 42%, p < 0.001) and were more likely to be on ibrutinib therapy (56% vs. 15%, p = 0.001).ConclusionsThis study confirms the safety and efficacy of the COVISHIELD™ vaccine in patients with hematological malignancies.

A comparison of a SARS-CoV-2 rapid-test and serological-test in a Public Health Hospital

Nowadays, with the start of the vaccination campaign is very important to assess the extent of exposure of the population and identifying rapid, sensitive and accurate test to quickly identify new cases of SARS-CoV-2. The rapid test, cheap and easy to perform, is therefore very useful in developing countries, where the vaccination campaign has not yet reached adequate coverage. We compared the VivaDiag COVID-19 IgM/IgG Rapid Test (VivaCheck Biotech Co., Ltd) with the Roche Elecsys Anti-SARS-CoV-2 (Roche Diagnostics, Rotkreuz, Switzerland) to recognize past infections and to compare VivaDiag COVID-19 IgM/IgG Rapid Test (VivaCheck Biotech Co., Ltd) with Abbott Real Time PCR SARS-CoV-2 assay to recognize infection during its acute phase so that it's possible to evaluate the use of commercially available assays in clinical practice. Of the 1,100 patients tested with serological and rapid test, 1,085 were negative both to serological and rapid test, 4 patients were positive at rapid (2 for IgM and 2 for IgG) but negative serological test, 11 patients were positive at serological test but negative to rapid. Of the 300 tested with oropharyngeal swab and rapid test, 294 were negative both to swab and rapid test, 2 positives both to swab and rapid test, 3 positives at swab but negative at rapid test, 1 negative at swab but positive at rapid test. the combined use of these tests according to the specific needs of users, allows a reliable identification of infected patients in the acute phase, distinguishing them from subjects with an antibody response from a previous infection.

SARS-CoV-2 Spike and Neutralizing Antibody Kinetics 90 Days after Three Doses of BNT162b2 mRNA COVID-19 Vaccine in Singapore.

Background: We evaluated the post-booster (BNT162b2) antibody responses in Singapore. Methods: Participants (n = 43) were tested pre-booster and 20/30/60/90 days post-booster. Participants were boosted 120–240 days (mean 214 days) after their second dose and had no history or serologic evidence of prior COVID-19 infection; all participants had undetectable SARS-CoV-2 nucleocapsid antibodies throughout the study. Total nucleocapsid and spike antibodies (S-Ab) were assessed on the Roche Elecsys e802 and neutralizing antibody (N-Ab) on the Snibe quantitative N-Ab assay. Results: Pre-booster median S-Ab/N-Ab titers were 829 BAU/mL/0.83 µg/mL; 2 participants were below manufacturer’s N-Ab cut-offs of 0.3 µg/mL (0.192 and 0.229). Both S-Ab and N-Ab titers peaked at 30 days post-booster (median S-Ab 25,220 BAU/mL and N-Ab 30.3 µg/mL) at 30–37× pre-booster median levels. These peak post-booster S-Ab/N-Ab titers were 11× (25,220 vs. 2235 BAU/mL) and 9× (30.3 vs. 3.52 µg/mL) higher than the previously reported peak post-second dose levels. Antibody titers declined to 12,315 BAU/mL (51% decrease) and 14.3 µg/mL (53% decrease) 90 days post-booster. Non-linear regression estimates for S-Ab/N-Ab half-lives were 44/58 days. At 180 days post-booster, S-Ab/N-Ab are estimated to be 2671 BAU/mL/4.83 µg/mL. Conclusions: Both S-Ab and N-Ab show a good response following post-booster vaccination, with half-lives that may provide a prolonged antibody response.

Abstract P4-10-03: Immunogenicity of SARS-CoV-2 vaccination in subjects on active treatment for breast cancer

Abstract Background: Infection with SARS-CoV-2 has led to a global pandemic and has significantly impacted the care of cancer patients. Breast cancer patients receiving active systemic therapy need protection against COVID19 but the efficacy of vaccines in this population is unknown. Although specific biomarkers associated with protection from SARS-CoV-2 infection have yet to be identified, measurement of serum antibody activity is generally accepted as a surrogate of in vivo humoral response to vaccine. This study evaluates the efficiency and durability of binding antibodies to SARS-CoV-2 spike (S) protein in response to COVID19 vaccine in breast cancer patients receiving systemic treatment. Methods: Breast cancer patients, who were unvaccinated, partially or fully vaccinated with Pfizer-BioNTech BNT162b2 (PF), Moderna mRNA-1273 (Mod) or Johnson &amp; Johnson AD26.COV2.S (J&amp;J) were enrolled in this prospective longitudinal study. Eligible patients were on systemic treatment with cytotoxic chemotherapy, chemotherapy plus a checkpoint inhibitor (CPI), CPI alone or a CDK 4/6 inhibitor. Longitudinal blood samples are being collected at baseline, prior to vaccination in unvaccinated patients (T0), 2 weeks after the first vaccine dose and before the second dose for the mRNA vaccines (T1), 1 month (T2), 3 months (T3), 6 months (T4) and 12 month post vaccination. For J&amp;J, there was no T1 timepoint. Roche Elecsys® Anti-SARS-CoV-2 S receptor binding domain (RBD) antibody immunoassay was used to measure antibody titers (range 0.4 to 250 U/mL). Cut points of &amp;lt;0.8 U/mL = negative, ≥0.8 U/mL = seropositive, were based on validated product specifications. Results: Of the 84 breast cancer patients enrolled, 9 had documented COVID infection at baseline and were excluded from analysis. Mean age was 58 years; 99% were female, 85% were Caucasian, 49% had early stage disease and 51% had metastatic breast cancer. 67% were receiving cytotoxic chemotherapy, 20% a CKD 4/6 inhibitor, 13% a CPI with or without chemotherapy. 61.2% were vaccinated with PF, 34.3% with Mod and 4.5% with J&amp;J vaccines. Seropositivity rate for the entire group was 10% at T0, 78% at T1, 98% at T2 and 100% at T3. Seropositivity rates of all cohorts at different timepoints are shown in the table. Mean titers for all patients were 12.6 U/mL at T0, 102.3 U/mL at T1, 204.4 U/mL at T2 and 214.6 U/mL at T3 timepoints. Similar incremental increase in antibody levels was observed in all cohorts (Table). Conclusions: 78% of the patients with breast cancer on active systemic treatment were seropositive after the first dose of COVID19 vaccine and 98% after the second dose. The antibody response was maintained at 3 months, with 100% seropositivity rate. 6-month antibody response will be available at the time of presentation. Durability of antibody response at 6 and 12 months will help determine the timing of additional vaccine booster doses in this population. Importantly, this study has found that active treatment with chemotherapy, immunotherapy or CDK4/6 inhibitor therapy does not impact antibody response to SARS-CoV-2 vaccination in patients with breast cancer. Table: Seropositivity rate and mean Anti-S protein antibody levels by cohort at each time point. T0= baseline, T1=after first vaccine dose (mRNA vaccines), T2= 4 weeks after 2 doses of mRNA vaccine or after single dose of J&amp;J vaccine, T3=3 months after the first dose of vaccine. N% Seropositive (&amp;gt;0.8 U/mL)Mean Antibody Levels (U/mL)T0T1T2T3T0T1T2T3All subjects7510789810012.6102.3204.4214.6Chemotherapy50577961003.3105.6200.0250CDK 4/6 inhibitors15257510010013.786.8234.7205.8CPI + Chemotherapy82583100NA*62.8121.4177.5NA*CPI therapy20100100NA*0.46.82250NA*CPI=Checkpoint Inhibitors; *Timepoint for longitudinal samples not reached Citation Format: Cory Bivona, Kevin Li, Priyanka Sharma, Jianghua He, Grace Martin, Andrew K Godwin, Anthony Rooney, Stephen Williamson, Gary Doolittle, Weijing Sun, Bruce F Kimler, Anne P O'Dea, Lauren E Nye, Joseph P McGuirk, Ziyan Pessetto, Lisa Haney, Nicole Balmaceda, Laura Mitchell, Karissa Finke, Maggie Nelson, Dinesh Pal Mudaranthakam, Natalie Streeter, Stephanie Lafaver, Jaimie Heldstab, Qamar J Khan. Immunogenicity of SARS-CoV-2 vaccination in subjects on active treatment for breast cancer [abstract]. In: Proceedings of the 2021 San Antonio Breast Cancer Symposium; 2021 Dec 7-10; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2022;82(4 Suppl):Abstract nr P4-10-03.

Abstract PD5-05: Impact of anti-HER2 therapy alone and in association with weekly paclitaxel on the ovarian reserve of young women with HER2-positive early breast cancer: Biomarker analysis of the NeoALTTO trial

Abstract Background: Knowledge regarding risk of treatment-induced premature ovarian insufficiency (POI) is crucial for appropriate oncofertility counseling. While the gonadotoxicity of anthracycline- and cyclophosphamide-based chemotherapy (CT) in young breast cancer (BC) patients (pts) is well established, the impact of anti-HER2 agents remains largely unknown and limited conflicting evidence exists for taxanes. Anti-Mullerian hormone (AMH) is an established biomarker of ovarian reserve; its measurements during systemic therapies may aid in diagnosis and prediction of POI. The NeoALTTO trial represented a unique setting to explore the acute gonadotoxicity of anti-HER2 therapy alone and in combination with weekly paclitaxel in pts not previously exposed to any other potentially gonadotoxic anticancer treatment. Methods: NeoALTTO (NCT00553358) is a multicenter, open-label, randomized phase III neoadjuvant trial in HER2-positive early BC pts randomized to receive lapatinib (L), trastuzumab (T), or their combination (L+T) alone for 6 weeks followed by the addition of paclitaxel for 12 weeks before surgery.The present analysis included only premenopausal women aged ≤45 years with available frozen serum samples at baseline (i.e. before administering any anticancer treatment), at week 2 (i.e. “biological window” of anti-HER2 therapy alone) and/or at surgery (i.e. after completion of paclitaxel plus anti-HER2 therapy). Central AMH testing was performed at Erasme Hospital (Brussels, Belgium) with the Roche Elecsys® AMH Plus assay (LoD=0.010 ng/ml). AMH levels during anti-HER2 therapy alone and then combined with paclitaxel were assessed as a measure of treatment impact on ovarian reserve. The impact of different anti-HER2 agents (T and/or L), pts’ age and baseline AMH levels on treatment gonadotoxicity were also investigated. Results: The present analysis included 130 pts with a median age of 38 years (IQR: 33-42 years), of whom 86 (66.2%) were ≤40 years. At baseline, median AMH levels were 1.29 ng/mL (IQR 0.56 - 2.62 ng/mL). At week 2, a small but significant reduction in AMH levels was observed (median value: 1.10 ng/mL, IQR 0.45 - 2.09 ng/mL, p&amp;lt;0.001; median cumulative decrease: -12.5%, IQR -37.6% - 12.4%). At surgery, there was a large significant decline in AMH levels (median value: 0.01 ng/mL, IQR 0.01 - 0.03 ng/mL, p&amp;lt;0.001; median cumulative decrease: -99.9%, IQR -100.0% - -98.7%). Type of anti-HER2 treatment (L vs. L vs. T+L) did not impact the results: there was no significant difference between treatment arms in degree of reduction in AMH levels at week 2 (p=0.763) or at surgery (p=0.700). Age and pre-treatment ovarian reserve had a major impact on treatment-induced gonadotoxicity risk, with a more profound decrease in AMH levels observed for older pts (p&amp;lt;0.001) and those with lower baseline AMH levels (p&amp;lt;0.001). Among pts aged &amp;lt;35 years, there was no significant difference in AMH levels between those with (n=7) or without (n=35) a subsequent pregnancy at baseline (p=0.316), week 2 (p=0.463) or at surgery (p=0.610). Conclusions: This biomarker analysis of the NeoALTTO trial showed for the first time the potential acute gonadal damage induced by anti-HER2 therapies alone and with the addition of weekly paclitaxel. We observed a small but significant reduction in AMH levels during T and/or L alone and then a profound reduction to almost undetectable levels following the addition of weekly paclitaxel, without differences by specific anti-HER2 regimen. Age and pre-treatment AMH levels strongly impacted gonadotoxicity risk. While this analysis is limited by lack of AMH measurement in longer term follow-up, findings have important implications for future research and oncofertility counseling of premenopausal women with HER2-positive BC. Citation Format: Matteo Lambertini, Marcello Ceppi, Richard A. Anderson, David A. Cameron, Marco Bruzzone, Maria Alice Franzoi, Claudia Massarotti, Sarra El-Abed, Yingbo Wang, Christophe Lecocq, Paolo Nuciforo, Rebecca Rolyance, Lajos Pusztai, Joohyuk Sohn, Jacopo Ligato, Maria Maddalena Latocca, Luca Arecco, Barbara Pistilli, Kathryn J. Ruddy, Alberto Ballestrero, Lucia Del Mastro, Fedro A. Peccatori, Ann H. Partridge, Cristina Saura, Michael Untch, Martine Piccart, Serena Di Cosimo, Evandro de Azambuja, Isabelle Demeestere. Impact of anti-HER2 therapy alone and in association with weekly paclitaxel on the ovarian reserve of young women with HER2-positive early breast cancer: Biomarker analysis of the NeoALTTO trial [abstract]. In: Proceedings of the 2021 San Antonio Breast Cancer Symposium; 2021 Dec 7-10; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2022;82(4 Suppl):Abstract nr PD5-05.