Comparison of five Anti-SARS-CoV-2 antibody assays across three doses of BNT162b2 reveals insufficient standardization of SARS-CoV-2 serology.

OBJECTIVES: To investigate the comparability of WHO standard referenced commercial SARS-CoV-2 antibody tests over three doses of BNT162b2 vaccine and up to 14 months. METHODS: 114 subjects (without previous SARS-CoV-2 infection or immunosuppressive medication) vaccinated with three doses of BNT162b2 were included in this study. Antibody levels were quantified 3 weeks after the first dose, 5-6 weeks and 7 months after the second dose, and 4-5 weeks and 4 months after the third dose using the Roche Elecsys SARS-CoV-2 S, the Abbott SARS-CoV-2 IgG II Quant, the DiaSorin LIAISON SARS-CoV-2 TrimericS IgG, the GenScript cPASS sVNT and the TECO sVNT assays. RESULTS: For each time point analyzed, systematic differences are evident between the results in BAU/mL of the three antibody binding assays. The assay ratios change in a time-dependent manner even beyond administering the third dose (Roche measuring 9 and 3 times higher than Abbott and DiaSorin, respectively). However, changes decrease in magnitude with increasing time intervals from the first dose. IgG-based assays show better agreement across them than with Roche (overall correlations: Abbott x DiaSorin: ρ = 0.94 vs. Abbott x Roche: ρ=0.89, p < 0.0001; DiaSorin x Roche: ρ = 0.87, p < 0.0001), but results are not interchangeable. The sVNTs suggest an underestimation of antibody levels by Roche and slight overestimation by both IgG assays after the first vaccine dose. CONCLUSIONS: Standardization of SARS-CoV-2 antibody binding assays still needs to be improved to allow reliable use of variable assay systems for longitudinal analyses.

Increasing test specificity without impairing sensitivity: lessons learned from SARS-CoV-2 serology.

BACKGROUND: Serological tests are widely used in various medical disciplines for diagnostic and monitoring purposes. Unfortunately, the sensitivity and specificity of test systems are often poor, leaving room for false-positive and false-negative results. However, conventional methods were used to increase specificity and decrease sensitivity and vice versa. Using SARS-CoV-2 serology as an example, we propose here a novel testing strategy: the 'sensitivity improved two-test' or 'SIT²' algorithm. METHODS: SIT² involves confirmatory retesting of samples with results falling in a predefined retesting zone of an initial screening test, with adjusted cut-offs to increase sensitivity. We verified and compared the performance of SIT² to single tests and orthogonal testing (OTA) in an Austrian cohort (1117 negative, 64 post-COVID-positive samples) and validated the algorithm in an independent British cohort (976 negatives and 536 positives). RESULTS: The specificity of SIT² was superior to single tests and non-inferior to OTA. The sensitivity was maintained or even improved using SIT² when compared with single tests or OTA. SIT² allowed correct identification of infected individuals even when a live virus neutralisation assay could not detect antibodies. Compared with single testing or OTA, SIT² significantly reduced total test errors to 0.46% (0.24-0.65) or 1.60% (0.94-2.38) at both 5% or 20% seroprevalence. CONCLUSION: For SARS-CoV-2 serology, SIT² proved to be the best diagnostic choice at both 5% and 20% seroprevalence in all tested scenarios. It is an easy to apply algorithm and can potentially be helpful for the serology of other infectious diseases.

Preanalytical stability of SARS-CoV-2 anti-nucleocapsid antibodies.

OBJECTIVES: Anti-nucleocapsid (NC) antibodies are produced in response to SARS-CoV-2 infection. Therefore, they are well suited for the detection of a previous infection. Especially in the case of seroprevalence studies or during the evaluation of a novel in-vitro diagnostic test, samples have been stored at <-70 °C (short- and long-term) or 2-10 °C (short-term) before analysis. This study aimed to assess the impact of different storage conditions relevant to routine biobanking on anti-NC antibodies. METHODS: The preanalytical impact of short-term storage (84 [58-98] days) on <-70 °C and for 14 days at 2-10 °C was evaluated using samples from 111 donors of the MedUni Vienna Biobank. Long-term effects (443 [409-468] days) were assessed using 208 samples from Biobank Graz and 49 samples from Biobank Vienna. Anti-Nucleocapsid antibodies were measured employing electrochemiluminescence assays (Roche Anti-SARS-CoV-2). RESULTS: After short-term storage, the observed changes did not exceed the extent that could be explained by analytical variability. In contrast, results after long-term storage were approximately 20% higher and seemed to increase with storage duration. This effect was independent of the biobank from which the samples were obtained. Accordingly, the sensitivity increased from 92.6 to 95.3% (p=0.008). However, comparisons with data from Anti-Spike protein assays, where these deviations were not apparent, suggest that this deviation could also be explained by the analytical variability of the qualitative Anti-NC assay. CONCLUSIONS: Results from anti-NC antibodies are stable during short-term storage at <-70 °C and 2-10 °C. After long-term storage, a slight increase in sensitivity could not be ruled out.

The Comparability of Anti-Spike SARS-CoV-2 Antibody Tests is Time-Dependent: a Prospective Observational Study.

Various commercial anti-Spike SARS-CoV-2 antibody tests are used for studies and in clinical settings after vaccination. An international standard for SARS-CoV-2 antibodies has been established to achieve comparability of such tests, allowing conversions to BAU/mL. This study aimed to investigate the comparability of antibody tests regarding the timing of blood collection after vaccination. For this prospective observational study, antibody levels of 50 participants with homologous AZD1222 vaccination were evaluated at 3 and 11 weeks after the first dose and 3 weeks after the second dose using two commercial anti-Spike binding antibody assays (Roche and Abbott) and a surrogate neutralization assay. The correlation between Roche and Abbott changed significantly depending on the time point studied. Although Abbott provided values three times higher than Roche 3 weeks after the first dose, the values for Roche were twice as high as for Abbott 11 weeks after the first dose and 5 to 6 times higher at 3 weeks after the second dose. The comparability of quantitative anti-Spike SARS-CoV-2 antibody tests was highly dependent on the timing of blood collection after vaccination. Therefore, standardization of the timing of blood collection might be necessary for the comparability of different quantitative SARS-COV-2 antibody assays. IMPORTANCE This work showed that the comparability of apparently standardized SARS-CoV-2 antibody assays (Roche, Abbott; both given in BAU/mL) after vaccination depends on the time of blood withdrawal. Initially (3 weeks after the first dose AZD1222), there were 3 times higher values in the Abbott assay, but this relationship inversed before boosting (11 weeks after the first dose) with Roche 2 times greater than Abbott. After the booster, Roche quantified ca. 5 times higher levels than Abbott. This must be considered by clinicians when interpreting SARS-CoV-2 antibody levels.

The comparability of Anti-Spike SARS-CoV-2 antibody tests is time-dependent: a prospective observational study

ObjectivesVarious commercial anti-Spike SARS-CoV-2 antibody tests are used for studies and in clinical settings after vaccination. An international standard for SARS-CoV-2 antibodies has been established to achieve comparability of such tests, allowing conversions to BAU/ml. This study aimed to investigate the comparability of antibody tests regarding the timing of blood collection after vaccination. MethodsFor this prospective observational study, antibody levels of 50 participants with homologous AZD1222 vaccination were evaluated at 3 and 11 weeks after the first dose and 3 weeks after the second dose using two commercial anti-Spike binding antibody assays (Roche and Abbott) and a surrogate neutralization assay. ResultsThe correlation between Roche and Abbott changed significantly depending on the time point studied. Although 3 weeks after the first dose, Abbott provided values three times higher than Roche, 11 weeks after the first dose, the values for Roche were twice as high as for Abbott, and 3 weeks after the second dose even 5-6 times higher. ConclusionsThe comparability of quantitative anti-Spike SARS-CoV-2 antibody tests is highly dependent on the timing of blood collection after vaccination. Therefore, standardization of the timing of blood collection might be necessary for the comparability of different quantitative SARS-COV-2 antibody assays. O_FIG O_LINKSMALLFIG WIDTH=200 HEIGHT=175 SRC="FIGDIR/small/21262426v1_ufig1.gif" ALT="Figure 1"> View larger version (27K): org.highwire.dtl.DTLVardef@1e789daorg.highwire.dtl.DTLVardef@b83aforg.highwire.dtl.DTLVardef@1f270daorg.highwire.dtl.DTLVardef@1cf296c_HPS_FORMAT_FIGEXP M_FIG C_FIG

Serum antibody response to BNT162b2 after natural SARS-CoV-2 infection.

BACKGROUND: There is preliminary evidence that individuals with previous SARS-CoV-2 infections exhibit a more pronounced antibody response. However, these assumptions have not yet been supported by data obtained through various CE-marked tests. This study aimed to close this gap. METHODS: Sixty-nine seronegatives and 12 individuals post-SARS-CoV-2 infection (tested by CE-labelled Roche NC immunoassay or PCR-confirmed assay) were included 21 ± 1 days after receiving the first dose of the Pfizer/BioNTech BNT162b2 vaccine. Antibody response to viral spike protein (S) was assessed by CE-labelled Roche S and DiaSorin S1/S2 assays and by a surrogate virus neutralization test (sVNT). RESULTS: After a single dose of BNT162b2, individuals after natural SARS-CoV-2 infection presented with markedly higher anti-S levels than naïve individuals (Roche S: 9078.5 BAU/mL [5267.0-24 298.5] vs 79.6 [24.7-142.3]; and DiaSorin S1/S2: 1465.0 AU/mL [631.0-5365.0] vs 63.7 [47.8-87.5]) and showed all the maximum observed inhibition activity in the sVNT (98%), without overlaps between groups. There was a trend for higher responses in those with a more distant infection, although not statistically significant. The relative antibody increase after dose 2 was significantly higher among naïve individuals (25-fold), but antibody levels remained below that of seropositives. CONCLUSIONS: Compared with naïve individuals, seropositives after natural SARS-CoV-2 infection presented with a substantially higher antibody response already after dose 1 of BNT162b2, as measured by two CE-marked in vitro diagnostic tests and a sVNT. These results should stimulate discussion and research on whether individuals after previous SARS-CoV-2 infection would benefit from a two-part vaccination schedule or whether these currently much-needed second doses could be saved.

Initial SARS-CoV-2 vaccination response can predict booster response for BNT162b2 but not for AZD1222.

OBJECTIVE: To determine whether severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) antibody levels after the first dose of vaccine can predict the final antibody response, and whether this is dependent on the vaccine type. METHODS: Sixty-nine recipients of BNT162b2 (Pfizer/BioNTech) and 55 recipients of AZD1222 (AstraZeneca), without previous infection or immunosuppressive medication, were included in this study. Antibody levels were quantified 3 weeks after the first dose [directly before boostering in the case of AZD1222 (11 weeks after the first dose)] and 3 weeks after the second dose using the Roche Elecsys SARS-CoV-2 S total antibody assay. RESULTS: Median pre-booster {BNT162b2: 80.6 [interquartile range (IQR) 25.5-167.0] binding antibody units (BAU)/mL; AZD1222: 56.4 (IQR 36.4-104.8) BAU/mL; not significant} and post-booster [BNT162b2: 2092.0 (IQR 1216.3-4431.8) BAU/mL; AZD1222: 957.0 (IQR 684.5-1684.8) BAU/mL; P<0.0001] levels correlated well in the recipients of BNT162b2 (ρ=0.53) but not in the recipients of AZD1222. Moreover, antibody levels after the first dose of BNT162b2 correlated inversely with age (ρ=-0.33, P=0.013), whereas a positive correlation with age was observed after the second dose in recipients of AZD1222 (ρ=0.26, P=0.030). CONCLUSIONS: The results of this study suggest that antibody levels quantified by the Roche Elecsys SARS-CoV-2 S assay before the booster shot could infer post-booster responses to BNT162b2, but not to AZ1222. In addition, this study found a vaccine-dependent effect on antibody responses, where age seems to play an ambivalent role.

Initial SARS-CoV-2 vaccination response can predict booster response for BNT162b2 but not for AZD1222

ObjectivesOur objective was to determine whether SARS-CoV-2 antibody levels after the first dose can predict the final antibody response and whether this is dependent on the vaccine type. Methods69 BNT162b2 (Pfizer/BioNTech) and 55 AZD1222 (AstraZeneca) vaccinees without previous infection or immunosuppressive medication were included. Anti-body levels were quantified 3 weeks after dose 1, in case of AZD1222 directly before boostering (11 weeks after dose 1) and 3 weeks after dose 2, with the Roche SARS-CoV-2 S total antibody assay. ResultsPre-booster (BNT162b2: 80.6 [25.5-167.0] BAU/mL, AZD1222: 56.4 [36.4-104.8] BAU/mL, not significant) and post-booster levels (BNT162b2: 2,092.0 [1,216.3-4,431.8] BAU/mL, AZD1222: 957.0 [684.5-1,684.8] BAU/mL, p<0.0001) correlated well in BNT162b2 ({rho}=0.53) but not in AZD1222 recipients. Moreover, antibody levels after the first dose of BNT162b2 correlated inversely with age ({rho}=-0.33, P=0.013), whereas a positive correlation with age was observed after the second dose in AZD1222 recipients ({rho}=0.26, P=0.030). ConclusionsIn conclusion, our data suggest that antibody levels quantified by the Roche Elecsys SARS-CoV-2 S assay before the booster shot could infer post-booster responses to BNT162b2, but not to AZ1222. In addition, we found a vaccine-dependent effect on antibody responses, suggesting a possible link between vaccine response and vector immunity.

Anti-Spike Protein Assays to Determine SARS-CoV-2 Antibody Levels: a Head-to-Head Comparison of Five Quantitative Assays.

Reliable quantification of the antibody response to severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is highly relevant, e.g., for identifying possible vaccine failure and estimating the time of protection. Therefore, we evaluated five different anti-SARS-CoV-2 antibody assays regarding the quantification of anti-spike (S) antibodies. Sera from 69 SARS-CoV-2-naive individuals 21 ± 1 days after vaccination with a single dose of BNT162b2 (Pfizer/BioNTech) were tested using the following quantitative assays: Roche S total antibody, DiaSorin trimeric spike IgG, DiaSorin S1/S2 IgG, Abbott II IgG, and Serion/Virion IgG. Results were further compared to the percent inhibition calculated from a surrogate virus neutralization test (sVNT). Individual values were distributed over several orders of magnitude for all assays. Although the assays were in good overall agreement (ρ = 0.80 to 0.94), Passing-Bablok regression revealed systematic constant and proportional differences, which could not be eliminated by converting the results to binding antibody units (BAU) per milliliter, as suggested by the manufacturers. Seven (10%) individuals had negative sVNT results (i.e., <30% inhibition). These samples were identified by most assays and yielded significantly lower binding antibody levels. Although all assays showed good correlation, they were not interchangeable, even when converted to BAU per milliliter using the WHO international standard for SARS-CoV-2 immunoglobulin. This highlights the need for further standardization of SARS-CoV-2 serology. IMPORTANCE Reliable quantification of the antibody response to SARS-CoV-2 is highly relevant, e.g., for identifying possible vaccine failure and estimating the time of protection. We compared the performance of five CE marked tests that quantify antibodies against the viral spike protein. Our findings suggest that, although all assays showed good correlation, their results were not interchangeable, even when converted to BAU per milliliter using the WHO international standard for SARS-CoV-2 immunoglobulin. This highlights the need for further standardization of SARS-CoV-2 serology.

Spike protein antibodies mediate the apparent correlation between SARS-CoV-2 nucleocapsid antibodies and neutralization test results

ObjectivesSARS-CoV-2 infection induces the formation of different antibodies. However, not all of which might prevent the virus from entering the cell, although their concentrations correlate with the titers of viral neutralization tests (NTs). Antibodies against the viral nucleocapsid (NC), e.g., can be classified as such. We aimed to prove the hypothesis that the apparent correlation between NC-antibody levels and NT-titers is mediated by simultaneously occurring antibodies against viral spike-protein components. MethodsWe included 64 individuals with previous SARS-CoV-2 infection (>14d after symptom onset). SARS-CoV-2 antibodies against the NC (Roche total antibody ECLIA, Abbott IgG CMIA) and spike-protein (Technozym RBD ELISA, DiaSorin S1/S2 CLIA) were measured, and neutralization tests were performed. The effect of spike-protein antibodies on the correlation between NC-antibodies and NT-titers was evaluated by partial correlation and mediation analyses. ResultsBoth tested assays assessing antibodies against the NC correlated significantly with NT titers: Abbott {rho}=0.742, P<0.0001; Roche {rho}=0.365, P<0.01. However, when controlling the rank correlations for the presence of RBD or S1/S2 antibodies, correlation coefficients dropped to {rho}=0.318/{rho}=0.329 (P<0.05/P<0.01), respectively for Abbott and vanished for Roche. As a result, only a maximum of 11% of NT titer variability could be explained by NC-antibody levels. ConclusionsOur data suggest that the apparent correlation between NC antibodies and NT titers is strongly mediated by co-occurring RBD antibody concentrations. To avoid falsely implied causal relationships, all correlation analyses of non-spike-associated antibody assays and neutralization assays should include a partial correlation analysis to exclude a possible mediator effect of spike-associated antibodies.

Basal myokine levels are associated with quality of life and depressed mood in older adults.

In an aging society, late-life depression has become an increasing problem. There is evidence that physical activity ameliorates depressive symptoms and increases the quality of life (QoL). However, the underlying mechanisms are still poorly understood. Myokines are molecules secreted in response to muscle contraction. Some of them can cross the blood-brain barrier, making them promising candidates for mediating the beneficial effects of physical activity on mood. The present study aims to compare circulating myokine levels to depression/QoL in older athletes and controls. 55 athletes, 57 controls >59 years were enrolled. The assessment included ergometry, magnetic resonance imaging, blood withdrawal, and neuropsychological testing. Serum interleukin-6 (IL-6), irisin, brain-derived neurotrophic factor (BDNF), kynurenine, and cathepsin B were analyzed and compared to surrogates of depression and quality of life. Athletes presented with higher levels of Cathepsin B. Among controls, all myokines but irisin were associated with age. Also, among controls, kynurenine and IL-6 correlated inversely with specific dimensions of quality of life questionnaires, and IL-6 further with depressive symptoms and decreased physical performance. No such associations could be found among athletes. Irisin levels were inversely associated with mild depression and low-grade white matter-lesions in the brain and predicted impaired QoL. The circulating levels of several myokines/muscle activity-related factors appear to be associated with depressive symptoms and impaired QoL among older adults. However, in athletes, some of these connections seem ameliorated, suggesting additional stressors (as f.e. age) or a different pathomechanism among athletes.

Anti-Spike protein assays to determine post-vaccination antibody levels: a head-to-head comparison of five quantitative assays

BackgroundReliable quantification of the antibody response to SARS-CoV-2 vaccination is highly relevant for identifying possible vaccine failure and estimating the time of protection. Therefore, we aimed to evaluate the performance of five different Anti-SARS-CoV-2 antibody assays regarding the quantification of anti-spike (S) antibodies induced after a single dose of BNT162b2. MethodsSera of n=69 SARS-CoV-2 naive individuals 21{+/-}1 days after vaccination with BNT162b2 (Pfizer/BioNTech) were tested using the following quantitative SARS-CoV-2 antibody assays: Roche S total antibody, DiaSorin trimeric spike IgG, DiaSorin S1/S2 IgG, Abbott II IgG, and Serion/Virion IgG. Test agreement was assessed by Passing-Bablok regression. Results were further compared to the percent inhibition calculated from a surrogate virus neutralization test (sVNT) by correlation and ROC (receiver-operating-characteristics) analysis. ResultsIndividual values were distributed over several orders of magnitude for all assays evaluated. Although the assays were in good overall agreement ({rho}=0.80-0.94), Passing-Bablok regression revealed systematic and proportional differences, which could not be eliminated by converting the results to BAU/mL as suggested by the manufacturers. 7 (10%) individuals had a negative sVNT results (i.e. <30% inhibition). These samples were reliably identified by most assays and yielded low binding antibody levels (ROC-AUCs 0.84-0.93). ConclusionsAlthough all assays evaluated showed good correlation, readings from different assays were not interchangeable, even when converted to BAU/mL using the WHO international standard for SARS-CoV-2 immunoglobulin. This highlights the need for further standardization of SARS-CoV-2 serology.

Increasing both specificity and sensitivity of SARS-CoV-2 antibody tests by using an adaptive orthogonal testing approach

BackgroundSerological tests are widely used in various medical disciplines for diagnostic and monitoring purposes. Unfortunately, the sensitivity and specificity of test systems is often poor, leaving room for false positive and false negative results. However, conventional methods used to increase specificity decrease sensitivity and vice versa. Using SARS-CoV-2 serology as an example, we propose here a novel testing strategy: the "Sensitivity Improved Two-Test" or " SIT2" algorithm. MethodsSIT2 involves confirmatory re-testing of samples with results falling in a predefined retesting-zone of an initial screening test, with adjusted cut-offs to increase sensitivity. We verified and compared the performance of SIT2 to single tests and orthogonal testing (OTA) in an Austrian cohort (1,117 negative, 64 post-COVID positive samples) and validated the algorithm in an independent British cohort (976 negatives, 536 positives). ResultsThe specificity of SIT2 was superior to single tests and non-inferior to OTA. The sensitivity was maintained or even improved using SIT2 when compared to single tests or OTA. SIT2 allowed correct identification of infected individuals even when a live virus neutralization assay could not detect antibodies. Compared to single testing or OTA, SIT2 significantly reduced total test errors to 0.46% (0.24-0.65) or 1.60% (0.94-2.38) at both 5% or 20% seroprevalence. ConclusionFor SARS-CoV-2 serology, SIT2 proved to be the best diagnostic choice at both 5% and 20% seroprevalence in all tested scenarios. It is an easy to apply algorithm and can potentially be helpful for the serology of other infectious diseases.

Side-by-Side Comparison of Three Fully Automated SARS-CoV-2 Antibody Assays with a Focus on Specificity.

BACKGROUND: In the context of the COVID-19 pandemic, numerous new serological test systems for the detection of anti-SARS-CoV-2 antibodies rapidly have become available. However, the clinical performance of many of these is still insufficiently described. Therefore, we compared 3 commercial CE-marked, SARS-CoV-2 antibody assays side by side. METHODS: We included a total of 1154 specimens from pre-COVID-19 times and 65 samples from COVID-19 patients (≥14 days after symptom onset) to evaluate the test performance of SARS-CoV-2 serological assays by Abbott, Roche, and DiaSorin. RESULTS: All 3 assays presented with high specificities: 99.2% (98.6-99.7) for Abbott, 99.7% (99.2-100.0) for Roche, and 98.3% (97.3-98.9) for DiaSorin. In contrast to the manufacturers' specifications, sensitivities only ranged from 83.1% to 89.2%. Although the 3 methods were in good agreement (Cohen's Kappa 0.71-0.87), McNemar tests revealed significant differences between results obtained from Roche and DiaSorin. However, at low seroprevalences, the minor differences in specificity resulted in profound discrepancies of positive predictive values at 1% seroprevalence: 52.3% (36.2-67.9), 77.6% (52.8-91.5), and 32.6% (23.6-43.1) for Abbott, Roche, and DiaSorin, respectively. CONCLUSION: We found diagnostically relevant differences in specificities for the anti-SARS-CoV-2 antibody assays by Abbott, Roche, and DiaSorin that have a significant impact on the positive predictive values of these tests.

Side by side comparison of three fully automated SARS-CoV-2 antibody assays with a focus on specificity

Background: In the context of the COVID-19 pandemic, numerous new serological test systems for the detection of anti-SARS-CoV-2 antibodies have become available quickly. However, the clinical performance of many of them is still insufficiently described. Therefore we compared three commercial, CE-marked, SARS-CoV-2 antibody assays side by side. Methods: We included a total of 1,154 specimens from pre-COVID-19 times and 65 samples from COVID-19 patients ([≥]14 days after symptom onset) to evaluate the test performance of SARS-CoV-2 serological assays by Abbott, Roche, and DiaSorin. Results: All three assays presented with high specificities: 99.2% (98.6-99.7) for Abbott, 99.7% (99.2-100.0) for Roche, and 98.3% (97.3-98.9) for DiaSorin. In contrast to the manufacturers specifications, sensitivities only ranged from 83.1% to 89.2%. Although the three methods were in good agreement (Cohens Kappa 0.71-0.87), McNemars test revealed significant differences between results obtained from Roche and DiaSorin. However, at low seroprevalences, the minor differences in specificity resulted in profound discrepancies of positive predictability at 1% seroprevalence: 52.3% (36.2-67.9), 77.6% (52.8-91.5), and 32.6% (23.6-43.1) for Abbott, Roche, and DiaSorin, respectively. Conclusion: We find diagnostically relevant differences in specificities for the anti-SARS-CoV-2 antibody assays by Abbott, Roche, and DiaSorin that have a significant impact on the positive predictability of these tests.

Type 2 diabetes care: Improvement by standardization at a diabetes rehabilitation clinic. An observational report.

BACKGROUND: Outcome of type 2 diabetes care depends on the acceptance of self-responsibility by informed patients, as treatment goals will otherwise be missed. AIMS AND METHODS: This pre/post-observational report describes the clinical outcome of type 2 diabetes care in patients with type 2 diabetes (N =930) admitted consecutively to a diabetes rehabilitation clinic (DRC) between June 2013, and June 2016, where they were exposed to standardized lifestyle modification with meals low in salt and rich in vegetables and fruits, totaling 1,200 to 1,600 kcal/d, and an add-on exercise load equivalent to 400-600 kcal/d. RESULTS: At admission, patients presented with multiple treatment modes, elevated HbA1c levels (7.6±1.5%, 60±16 mmol/mol), a high prevalence of co-morbidities dominated by obesity (79%), a low rate of influenza and pneumococcal immunization (<9%) and underuse of lipid-lowering drugs (-29%). Analysis of clinical and metabolic outcome after 3 weeks shows that simple standardization of and better adherence to treatment recommendations improved (p<0.0001) glucose (HbA1c -0.4±0.4%) and lipid metabolism (LDL/HDL ratio, -0.58±0.03), permitting a 39% reduction in insulin dosage, omission of insulin in 36/232 patients and omission of oral antidiabetic drugs (OADs) other than metformin and DPP4-inhibitors, while the use of GLP-1 analogs doubled to 5.2%. Improved outcome was independent of treatment strategy and more marked at initially high HbA1c at costs less than 25% of those encountered at a standard hospital. CONCLUSIONS: Our observations support the clinical notion that adherence to basic treatment recommendations is indispensable in type 2 diabetes care if metabolic and clinical treatment goals are to be met, and if inappropriate add-on over-medicalization with OADs and/or insulin is to be avoided. To this end, 'imprinting' patients at a DRC could be of considerable help.

Obesity: outcome of standardized life-style change in a rehabilitation clinic. An observational study.

Purpose: To explore differences in baseline characteristics following three weeks of semi-standardized in-patient care between patients with obesity without and with type 2 diabetes (T2D). Patients and methods: Patients without or with T2D were matched according to age, sex, and BMI. Food intake was restricted to 1,200-1,600 kcal/d to which a 400-600 kcal/d exercise load was added, and data were compared using Student's t-test, general linear models, and Spearman-rank correlations. Results: At baseline, patients with obesity and T2D displayed, besides elevated blood glucose and HbA1c values, higher serum liver enzymes (p<0.001-0.05), triglycerides, and CRP (p<0.01) and a greater prevalence of treated hyperlipidemia (p<0.001) than those with plain obesity who showed only higher LDL and HDL cholesterol levels (+9.0% and +16.0%). In response to three-weeks of standardized life-style change, both groups improved their vital variables and risk scores (p<0.001). While improvement in cholesterol slightly favored patients with plain obesity, the need for anti-hyperlipidemics (+25%) rose in both groups, albeit that for anti-hypertensives (+50%) increased only in patients with obesity and add-on T2D. Conclusion: Moderate changes in lifestyle improve the clinical condition, including coronary heart disease and premature mortality risk scores (HARD-CHD and ABSI) in patients with obesity both in the absence and presence of T2D, with the latter seemingly increasing the risk of hepatic steatosis and systemic inflammation.

Usage Data and Scientific Impact of the Prospectively Established Fluid Bioresources at the Hospital-Based MedUni Wien Biobank.

Background and Aim: It is increasingly recognized that biomedical research has serious reproducibility issues, which could be overcome at least in part by standardized processing of biomaterials. Therefore, professional biobanks have emerged, positively influencing sample and data quality. However, quantitative data about a biobank's contribution to published results are still hard to find, although they could serve as valuable benchmark figures for the community. We therefore aimed to report usage data from the MedUni Wien Biobank facility regarding its prospective fluid cohorts. Methods: Input and access statistics and publication output were reported for the years 2010-2017. Performance dynamics were tested by correlation analyses according to Spearman. Additionally, virtual costs per sample were calculated. Results: The amount of annually collected aliquots rose significantly from 68,500 in 2010 to 151,966 in 2017 (p = 0.015), although no further increase was recorded after 2012 (p = 0.266). In the same period, the quotient of requested to stored aliquots increased from 3.5% to 6.1% (p = 0.001), as the yearly number of requested aliquots nearly quadrupled from 2401 to 9342. Likewise, the number of published research articles per year to which the MedUni Wien Biobank contributed increased from 2 (total impact factor: 8.6) in 2010 to 16 (total impact factor: 69.0) in 2017, resulting in a total of 69 identified publications. Currently, the biobank operates at 15- to 20-fold overproduction, leading to virtual costs per accessed sample of ∼€20. Conclusion: The reported usage data might serve as a benchmark for other hospital-integrated biobanks, and implies that academic biobanks are able to produce considerable scientific impact at comparable moderate costs.

Type 1 diabetes care: Improvement by standardization in a diabetes rehabilitation clinic. An observational report.

BACKGROUND: T1D treatment requires informed self-responsible patients, who, however, frequently miss their therapeutic goals, providing considerable potential for improvement. METHODS: This observational report evaluates T1D patients [N = 109], aged ≥18 years (range 22-82), poorly controlled at home, at and 3 weeks after their admission to our diabetes rehabilitation clinic [DRC], where they were offered standardized, but unmonitored life-style modification. RESULTS: At admission, patients displayed elevated HbA1c values (66 mmol/mol [57; 81]), a high prevalence of co-morbidities (88%), lipodystrophies due to monolocal insulin injections (42%), a low rate of influenza (16%) and pneumococcal (7%) immunization, and underuse of lipid-lowering drugs (-38%). Standardization of life-style improved glucose (p<0.0001) and lipid metabolism (LDL/HDL ratio p<0.01) permitting reduction of insulin dose and reduction of add-on glucose-lowering drugs (GLDs) other than metformin. Outcome was independent of the mode of insulin treatment strategy and more marked at initially high HbA1c, with DRC-costs/d less than 25% of those encountered at standard hospitals. CONCLUSION: Type 1 diabetes care requires i) insulin treatment, food intake and life style to be handled in concert, ii) this need cannot be replaced by arbitrary addition of add-on GLDs, and iii) training to this end is 75% cheaper at a DRC than in standard hospitals.