Multiparametric Prediction Models for Coronavirus Disease 2019 Vaccine Selection: Results of a Comparative Population-Based Cohort Study.

BACKGROUND: An understanding vaccine-dependent effects on protective and sustained humoral immune response is crucial to planning future vaccination strategies against coronavirus disease 2019 (COVID-19). METHODS: In this multicenter, population-based, cohort study including 4601 individuals after primary vaccination against COVID-19 ≥ 4 months earlier we compared factors associated with residual antibody levels against severe acute respiratory syndrome coronavirus-2 receptor-binding domain (RBD) across different vaccination strategies (BNT162b2, mRNA-1273, or ChAdOx1). RESULTS: Our main model including 3787 individuals (2 × BNT162b2, n = 2271; 2 × mRNA-1273, n = 251; 2 × ChAdOx1, n = 1265), predicted significantly lower levels of anti-RBD antibodies after 6 months in individuals vaccinated with ChAdOx1 (392.7 binding antibody units per milliliter [BAU/mL]) compared with those vaccinated with BNT162b2 (1179.5 BAU/mL) or mRNA-1273 (2098.2 BAU/mL). Vaccine-dependent association of antibody levels was found for age with a significant predicted difference in BAU/ml per year for BNT162b2 (-21.5; 95% confidence interval [CI], -24.7 to -18.3) and no significant association for mRNA-1273 (-4.0; 95% CI, -20.0 to 12.1) or ChAdOx1 (1.7; 95% CI, .2 to 3.1). The predicted decrease over time since full immunization was highest in mRNA-1273 (-23.4; 95% CI, -31.4 to -15.4) compared with BNT162b2 (-5.9; 95% CI, -7 to -4.8). CONCLUSIONS: Our study revealed population-based evidence of vaccine-dependent effects of age and time since full immunization on humoral immune response. Findings underline the importance of individualized vaccine selection, especially in elderly individuals.

Enriched stable 204Pb as tracer at ultra-low levels in clinical investigations.

The potential of enriched Pb (204Pb) was assessed to monitor pathways of trace levels of Pb in the pg range within the human body via isotope pattern variation in situations where natural lead cannot be used as a tracer due to regulatory limitations. Isotope ratio measurements were accomplished by means of (multi-collector) inductively coupled plasma mass spectrometry including a comparison of single and multi-collector ICP-MS for low-level 204Pb assessment. Isotopic pattern results from a blend of a large quantity of the element with a natural isotopic composition and an enriched stable isotope at orders of magnitude lower levels pose a nontrivial analytical problem. Isotope pattern deconvolution was successfully applied as mathematical tool based on multiple linear regressions. The method allowed for deconvolving the isotope pattern from measured isotope ratios without knowing the quantities of different isotope sources incorporated and mixed into the sample at levels of < 1 pg 204Pb/g blood. The objective of this manuscript is to evaluate and summarize the analytical aspects for Pb isotope pattern deconvolution based on the results of a clinical trial, where a 204Pb-enriched isotope tracer was applied to investigate the bioavailability of orally applied Pb along with purified clinoptilolite tuff as potential supplement. This unique approach allows to reduce tracer amounts to harmless levels to human health, which are in accordance with the legal regulative to study enrichment levels of < 0.01% in human blood.

Antibiotic prescription after tooth extraction in adults: a retrospective cohort study in Austria.

BACKGROUND: Broad spectrum antibiotics are often used for the prophylaxis of infectious endocarditis and treatment of odontogenic infections, but there are limited data related to antibiotic use and adherence to prescription guidelines.  METHODS: Data from patients with tooth extraction between 2014 and 2018 were selected from a database of a regional health insurance fund. We created three data sets, one based on all tooth extractions, one on multiple teeth extractions, and one including only single tooth extraction. After data collection, descriptive analysis was carried out. The differences in prescription pattern of antibiotic medicine were tested by χ2 test, Student´s t-test or ANOVA. RESULTS: From 43,863 patients with tooth extraction, 53% were female, and 3,983 patients (9.1%) filled a prescription for antibiotic medicine. From 43,863 patients, 157 patients (0.4%) had endocarditis risk, but only 8 patients of these (5.1%) filled an antibiotic prescription. In total, 9,234 patients had multiple and 34,437 patients had only one tooth extraction. Patients with more than one tooth extraction received more often antibiotic treatment (10.7%) compared to those with single tooth extractions (χ2 = 36; p < 0,001). Patients with more than one tooth extraction were older, however, younger patients received antibiotics more frequently (t = 28,774, p = 0.001). There was no relationship with endocarditis risk status. Clindamycin and amoxicillin/clavulanic acid were the most frequently prescribed antibiotic medicines. CONCLUSIONS: In this retrospective cohort study, dentists did not discriminate prophylactic antibiotic prescription with regard to endocarditis risk status. A factor influencing prescribing behaviour of antibiotic medicines was the number of extracted teeth.

Immunogenicity and safety of COVID-19 booster vaccination: A population-based clinical trial to identify the best vaccination strategy.

BACKGROUND: Various SARS-CoV-2 variants of concerns (VOCs) characterized by higher transmissibility and immune evasion have emerged. Despite reduced vaccine efficacy against VOCs, currently available vaccines provide protection. Population-based evidence on the humoral immune response after booster vaccination is crucial to guide future vaccination strategies and in preparation for imminent COVID-19 waves. METHODS: This multicenter, population-based cohort study included 4697 individuals ≥18 years of age who received a booster vaccination. Antibody levels against SARS-CoV-2 receptor binding domain (RBD) and neutralizing antibodies against wild-type (WT) virus and Omicron variants were assessed at baseline (day of booster vaccination) and after four weeks. Safety was evaluated daily within the first week using a participant-completed electronic diary. Antibody levels were compared across different vaccination strategies, taking into account individual host factors. RESULTS: Our main model including 3838 participants revealed that individuals who received a booster with mRNA-1273 compared to BNT162b2 vaccine had a significantly higher increase (95 %CI) in anti-RBD-antibody levels (37,707 BAU/mL [34,575-40,839] vs. 27,176 BAU/mL [26,265-28,087]), and of neutralization levels against WT (1,681 [1490-1872] vs. 1141 [1004-1278] and Omicron variant (422 [369-474] vs. 329 [284-374]). Neutralizing antibody titres highly correlated with anti-RBD antibodies, with neutralizing capacity 4.4 fold higher against WT compared to Omicron. No differences in safety were found between the two booster vaccines. CONCLUSION: Our study underlines the superiority of a booster vaccination with mRNA-1273, independent of the primary vaccination and therefore provides guidance on the vaccination strategy.

Reduced immunogenicity of BNT162b2 booster vaccination in combination with a tetravalent influenza vaccination: results of a prospective cohort study in 838 health workers.

OBJECTIVE: To investigate the immunogenicity and safety of BNT162b2 booster vaccination with and without a tetravalent influenza vaccine. METHODS: A prospective, open-label cohort study on immunogenicity and safety of COVID-19 booster vaccination with or without a tetravalent influenza vaccine was performed. Eight hundred thirty-eight health care workers were included in the following study arms: BNT162b2 booster-only, influenza-vaccine-only or combination of both. Levels of antibodies against SARS-CoV-2 spike receptor binding domain, and haemagglutinin inhibition tested for four different influenza strains (A(H1N1)pdm09, A(H3N2), B/Victoria, B/Yamagata) were measured at the time of vaccination and 4 weeks later. RESULTS: After 4 weeks, median (interquartile range) levels of antibodies against the receptor binding domain of the viral spike (S) protein and relative change from baseline were high in individuals who received BNTb162b2 booster vaccination only (absolute: 16 600 [10 980-24 360] vs. 12 630 [8198-18 750] BAU/mL [p < 0.0001]; relative increase: 49% [23.6-95.3] vs. 40% [21.9-80.6] [p 0.048]; booster-only n = 521 vs. combination-arm n = 229 respectively). Results were confirmed after matching for sex, age, body mass index, baseline antibody levels and vaccine compound received for primary immunization (absolute: 13 930 [10 610-22 760] vs. 12 520 [8710-17 940]; [p 0.031]; relative increase: 55.7% [27.8-98.5] vs. 42.2% [22.9-74.5]; p 0.045). Adverse events were almost identical in the booster-only and the combination-arm, but numerically low in the influenza arm (525/536 [97.9%] vs. 235/240 [97.9%] vs. 26/33 [78.8 %]). DISCUSSION: Although no safety concerns occurred, our study provides evidence on reduced immunogenicity of a BNT162b2 booster vaccination in combination with a tetravalent influenza vaccine. Further studies investigating new influenza variants as well as potential differences vaccine effectiveness are needed.

Safety and efficacy of purified clinoptilolite-tuff treatment in patients with irritable bowel syndrome with diarrhea: Randomized controlled trial.

BACKGROUND: Irritable bowel syndrome (IBS) is a highly prevalent gastrointestinal disorder with poor response to treatment. IBS with predominant diarrhea (IBS-D) is accompanied by abdominal pain as well as high stool frequency and urgency. Purified clinoptilolite-tuff (PCT), which is approved by the Food and Drug Administration for use as a dietary supplement with the brand name G-PUR®, has previously shown therapeutic potential in other indications based on its physical adsorption capacity. AIM: To assess whether symptoms of IBS-D can be ameliorated by oral treatment with PCT. METHODS: In this randomized, placebo-controlled, double-blind pilot study, 30 patients with IBS-D diagnosis based on Rome IV criteria were enrolled. Following a 4-wk run-in phase, 14 patients were randomized to receive a 12-wk treatment with G-PUR® (2 g three times daily), and 16 patients received placebo. The relief from IBS-D symptoms as measured by the proportion of responders according to the Subject's Global Assessment (SGA) of Relief was assessed as the primary outcome. For the secondary outcomes, validated IBS-D associated symptom questionnaires, exploratory biomarkers and microbiome data were collected. RESULTS: The proportions of SGA of Relief responders after 12 wk were comparable in both groups, namely 21% in the G-PUR® group and 25% in the placebo group. After 4 wk of treatment, 36% of patients in the G-PUR® group vs 0% in the placebo group reported complete or considerable relief. An improvement in daily abdominal pain was noted in 94% vs 83% (P = 0.0353), and the median number of days with diarrhea per week decreased by 2.4 d vs 0.3 d in the G-PUR® and placebo groups, respectively. Positive trends were observed for 50% of responders in the Bristol Stool Form Scale. Positive trends were also noted for combined abdominal pain and stool consistency response and the Perceived Stress Questionnaire score. Only 64% in the G-PUR® group compared to 86% in the placebo group required rescue medication intake during the study. Stool microbiome studies showed a minor increase in diversity in the G-PUR® group but not in the placebo group. No PCT-related serious adverse events were reported. CONCLUSION: In this randomized, double-blind, placebo-controlled study, the PCT product, G-PUR®, demonstrated safety and clinical benefit towards some symptoms of IBS-D, representing a promising novel treatment option for these patients.

Sensitivity and Specificity of SARS-CoV-2 Rapid Antigen Detection Tests Using Oral, Anterior Nasal, and Nasopharyngeal Swabs: a Diagnostic Accuracy Study.

The objective of our study was to evaluate the sensitivity and specificity of rapid antigen detection tests versus those of reverse transcriptase PCR (RT-PCR) using oral, anterior nasal, and nasopharyngeal swabs. The underlying prospective, diagnostic case-control-type accuracy study included 87 hospitalized and nonhospitalized participants in a positive and a negative sample cohort between 16 March and 14 May 2021 in two hospitals in Vienna. SARS-CoV-2 infection status was confirmed by RT-PCR. Participants self-performed one oral and one anterior nasal swab for the rapid antigen test, immediately followed by two nasopharyngeal swabs for the rapid antigen test and RT-PCR by the investigator. Test results were read after 15 min, and participants completed a questionnaire in the meantime. Test parameters were calculated based on the evaluation of 87 participants. The overall sensitivity of rapid antigen detection tests versus that of RT-PCR with oral, anterior nasal, and nasopharyngeal samples was 18.18% (95% confidence interval [CI] 8.19% to 32.71%), 63.04% (95% CI 47.55% to 76.79%), and 73.33% (95% CI 58.06% to 85.4%), respectively. All sampling methods had a test specificity of 100% regardless of the cycle threshold (CT) value. Rapid antigen detection tests using self-collected anterior nasal swabs proved to be as sensitive as and more tolerable than professionally collected nasopharyngeal swabs for CT values up to 30 determined by RT-PCR. This finding illustrates the reliability of tests obtained by adequate self-collected anterior nasal specimen. Sensitivity was dependent upon the CT value for each sampling method. While the main advantage of rapid antigen detection tests is the immediate availability of results, PCR should be preferred in crucial settings wherever possible. IMPORTANCE Rapid antigen detection devices for SARS-CoV-2 represent a valuable tool for monitoring the spread of infection. However, the reliability of the tests depends largely on the test performance and the respective sampling method. Nasopharyngeal swabs mark the gold standard for sample collection in suspected respiratory tract infections but are unsuitable for widespread application, as they must be performed by medically trained personnel. With the underlying study, the head-to-head test performance and the usability of self-collected samples for SARS-CoV-2 detection using rapid antigen detection devices were evaluated. The results confirm similar sensitivity of self-collected anterior nasal swabs to that of professionally collected nasopharyngeal swabs for patients with a CT of < 30 determined by RT-PCR.

COVID-19 as a putative trigger of anti-MDA5-associated dermatomyositis with acute respiratory distress syndrome (ARDS) requiring lung transplantation, a case report.

BACKGROUND: Autoimmune disease following COVID-19 has been studied intensely since the beginning of the pandemic. Growing evidence indicates that SARS-CoV-2 infection, by virtue of molecular mimicry can lead to an antigen-mediated cross-reaction promoting the development of a plethora of autoimmune spectrum diseases involving lungs and extrapulmonary tissues alike. In both COVID-19 and autoimmune disease, the immune self-tolerance breaks, leading to an overreaction of the immune system with production of a variety of autoantibodies, sharing similarities in clinical manifestation, laboratory, imaging, and pathology findings. Anti-Melanoma Differentiation-Associated gene 5 dermatomyositis (anti-MDA5 DM) comprises a rare subtype of systemic inflammatory myopathies associated with characteristic cutaneous features and life-threatening rapidly progressive interstitial lung disease (RP-ILD). The production of anti-MDA5 autoantibodies was proposed to be triggered by viral infections. CASE PRESENTATION: A 20-year-old male patient with polyarthritis, fatigue and exertional dyspnea was referred to our department. An elevated anti-MDA5 autoantibody titer, myositis on MRI, ground glass opacifications on lung CT and histological features of Wong-type dermatomyositis were confirmed, suggesting the diagnosis of an anti-MDA5 DM. Amid further diagnostic procedures, a serologic proof of a recent SARS-CoV-2 infection emerged. Subsequently, the patient deteriorated into a fulminant respiratory failure and an urgent lung transplantation was performed, leading to remission ever since (i.e. 12 months as of now). CONCLUSIONS: We report a unique case of a patient with a new-onset anti-MDA5 DM with fulminant ARDS emerging in a post-infectious stage of COVID-19, who underwent a successful lung transplantation and achieved remission. Given the high mortality of anti-MDA5 DM associated RP-ILD, we would like to highlight that the timely recognition of this condition and urgent therapy initiation are of utmost importance.