Screening and Confirmatory Testing for SARS-CoV-2 Antibodies: Comparison of Health and Non-Health Workers in a Nationwide Healthcare Organization in Central Europe

Despite being located close to the European epicenter of the COVID-19 pandemic in Italy, Austria has managed to control the first wave. In Austria, the largest health insurance fund covers 7 million people and has 12,000 employees, including 3700 healthcare workers (HCW). For patient and staff safety, transmission control measures were implemented and mass testing of employees for SARS-CoV-2 antibodies was conducted. An IgG SARS-CoV-2 rapid test on fingerstick blood was used as a screening test (ST), followed by serologic studies with 3 different immunoassays and confirmatory testing by a neutralization test (NT). Among 7858 employees, 144 had a positive ST and 88 were confirmed by a NT (1.12%, CI: 0.9–1.38%). The positive predictive value (PPV) of the ST was 69.3% (CI: 60.5–77.2). Interestingly, 40% of the NT positive serum samples were tested negative in all 3 immunoassays. Of the total sample, 2242 HCW (28.5%) were identified. Unexpectedly, there was no difference in the prevalence of NT positives in HCW compared to non-HCW (23/2242 vs. 65/5301, p = 0.53). SARS-CoV-2 antibody prevalence was not increased among HCW. Although HCW are at potentially increased risk for SARS-CoV-2 infection, transmission control measures in healthcare facilities appear sufficient to limit transmission of infection

Effects of dexamethasone on endotoxin induced pulmonary inflammation and coagulation

Hintergrund: Eine broncho-alveolare Instillation von Endotoxin induziert eine Entzündungsreaktion in der Lunge, welche sich im kinetischen und qualitativen Verlauf von einer systemischen (intravenösen) Verabreichung unterscheidet. In der Lungenheilkunde werden Kortikosteroide häufig als entzündungshemmende Medikamente eingesetzt, jedoch gibt es nur sehr begrenzte Daten über ihr Wirkungsprofil im Lungenkompartiment. Eine Entzündungsreaktion ist generell mit einer Aktivierung des Gerinnungssystems vergesellschaftet und es gibt Hinweise darauf, dass Kortikosteroide, besonders im Kontext einer akuten Phase Reaktion, prokoagulatorisch wirken. Wir untersuchten die Auswirkungen von Kortikosteroid-Infusionen auf die pulmonale Inflammation und Gerinnung. Methoden: Eine randomisierte, doppelblinde und Placebo-kontrollierte Studie wurde an 24 gesunden Probanden durchgeführt, die Dexamethason oder Placebo erhielten. Eine sterile, milde Lungenentzündung wurde durch Endotoxin-Instillation in rechte oder linke Lungensegmente induziert, gefolgt von Kochsalzlösung Instillation in die kontralaterale Seite. Eine bilaterale bronchoalveoläre Lavage (BAL) wurde sechs Stunden danach durchgeführt. Ergebnisse: Die Instillation von Endotoxin induzierte eine entzündliche und pro-koagulierende Reaktion in der Lunge. Obwohl Dexamethason effektiv Interleukin (IL) 6 und C-reaktive Proteinkonzentrationen im Serum reduzierte, waren Zytokine wie IL-6 und IL-8 in der BAL fast unverändert. Dexamethason inhibierte den Endotoxin-induzierten Anstieg der BAL-Zellularität und des Gesamtproteins. Dennoch wurden Marker der aktivierten Gerinnung in der BAL der Dexamethason-Gruppe im Vergleich zu Placebo reduziert. Schlussfolgerungen: Dexamethason hatte nur erstaunlich wenig Auswirkungen auf die pulmonale Zytokinfreisetzung, während die Aktivierung der Gerinnung unterdrückt wurde. Dies wurde wahrscheinlich durch die Hemmung der Proteinextravasation verursacht.Background: Broncho-alveolar instillation of endotoxin induces an inflammatory response in the lung with a different kinetic and qualitative course compared to systemic endotoxin challenge. Corticosteroids are commonly used anti-inflammatory agents in respiratory diseases but there is only very limited data on their pharmacodynamic profile in the lungs. Inflammation closely interacts with the coagulation system and there is evidence that corticosteroids cause a systemic procoagulant state in the setting of inflammation. We investigated the effects of glucocorticoid infusions on endotoxin stimulated lung inflammation and coagulation. Methods: A randomized, double-blind and placebo-controlled trial was conducted in twenty-four healthy volunteers who received dexamethasone or placebo. Lung inflammation was induced by endotoxin instillation into right or left pulmonary segments, followed by saline into the contralateral site. A bilateral bronchoalveolar lavage was performed six hours thereafter. Results: Instillation of endotoxin induced an inflammatory and pro-coagulant response in the lung. Though dexamethasone effectively reduced interleukin 6 and C-reactive protein concentrations in serum, cytokines such as interleukin 6 and interleukin 8 were almost unaltered in bronchoalveolar lavage. Dexamethasone inhibited endotoxininduced increases in bronchoalveolar lavage white blood cell counts and total protein. Markers of activated coagulation were reduced in bronchoalveolar lavage of the dexamethasone group when compared with placebo. Conclusions: Dexamethasone had limited effects on pulmonary cytokine release whereas activation of coagulation was suppressed. This was likely caused by inhibition of protein extravasation.submitted by Johann BartkoAbweichender Titel laut Übersetzung der Verfasserin/des VerfassersMedizinische Universität Wien, Dissertation, 2017OeBB(VLID)266763

The use of frozen plasma samples in thromboelastometry

Thromboelastometry is increasingly used in the clinical and scientific setting. The use of frozen plasma samples may be useful in overcoming certain limitations such as local and timely availability. Whole blood (WB) samples of 20 healthy volunteers were obtained, and plasma was generated. NATEM (n = 20), EXTEM (n = 20) and INTEM (n = 8) analyses were performed in WB, fresh plasma and frozen and thawed plasma. Dabigatran (500, 1000 ng/ml), rivaroxaban (100, 200 ng/ml) or alteplase (333 ng/ml) were added ex vivo to WB, and thromboelastometry was performed in WB and in frozen and thawed plasma samples. Clot formation time, mean clot firmness and the area under the curve were significantly altered in plasma compared to WB. In INTEM and EXTEM analysis, clotting time (CT) was comparable between WB (100%) and fresh (INTEM 114% and EXTEM 93%, ratio of the means) and frozen plasma samples (85 and 99%), whereas in NATEM analysis, the CT increased in fresh (193%) and frozen plasma samples (130%). Dabigatran dose-dependently increased the CT approximately 5- and 9-fold in WB and even more pronounced 10- and 26-fold in plasma. Accordingly, rivaroxaban dose-dependently increased the CT 2- and 2.7-fold in WB, and 3.5- and 4-fold in plasma samples. Hyperfibrinolysis was achieved by addition of alteplase in all WB samples and was reproducible in plasma samples. In conclusion, thromboelastometry, especially INTEM and EXTEM analyses, is possible using frozen and stored plasma samples with comparable results to the corresponding whole blood samples.(VLID)355922

British Journal of Clinical Pharmacology / Dissociation between systemic and pulmonary anti-inflammatory effects of dexamethasone in humans

AIMS The local pulmonary inflammatory response has a different temporal and qualitative profile compared with the systemic inflammatory response. Although glucocorticoids substantially downregulate the systemic release of acute-phase mediators, it is not clear whether they have comparable inhibitory effects in the human lung compartment. Therefore, we compared the anti-inflammatory effects of a pure glucocorticoid agonist, dexamethasone, on bronchoalveolar lavage and blood cytokine concentrations in response to bronchially instilled endotoxin. METHODS In this randomized, double-blind and placebo-controlled trial, 24 volunteers received dexamethasone or placebo and had endotoxin instilled into a lung segment and saline instilled into a contralateral segment, followed by bronchoalveolar lavage. RESULTS Bronchially instilled endotoxin induced a local and systemic inflammatory response. Dexamethasone strongly blunted the systemic interleukin (IL) 6 and C-reactive protein release. In sharp contrast, dexamethasone left the local release of acute-phase mediators in the lungs virtually unchanged: bronchoalveolar lavage levels of IL-6 were only 18% lower and levels of IL-8 were even higher with dexamethasone compared with placebo, although the differences between treatments were not statistically significant (P = 0.07 and P = 0.08, respectively). However, dexamethasone had inhibitory effects on pulmonary protein extravasation and neutrophil migration. CONCLUSIONS The present study demonstrated a remarkable dissociation between the systemic anti-inflammatory effects of glucocorticoids and its protective effects on capillary leak on the one hand and surprisingly low anti-inflammatory effects in the lungs on the other.F 5404-B21(VLID)310833

Effect of ischemic preconditioning in skeletal muscle measured by functional magnetic resonance imaging and spectroscopy: a randomized crossover trial

<p>Abstract</p> <p>Background</p> <p>Nuclear magnetic resonance (NMR) imaging and spectroscopy have been applied to assess skeletal muscle oxidative metabolism. Therefore, in-vivo NMR may enable the characterization of ischemia-reperfusion injury. The goal of this study was to evaluate whether NMR could detect the effects of ischemic preconditioning (IPC) in healthy subjects.</p> <p>Methods</p> <p>Twenty-three participants were included in two randomized crossover protocols in which the effects of IPC were measured by NMR and muscle force assessments. Leg ischemia was administered for 20 minutes with or without a subsequent impaired reperfusion for 5 minutes (stenosis model). IPC was administered 4 or 48 hours prior to ischemia. Changes in ³¹phosphate NMR spectroscopy and blood oxygen level-dependent (BOLD) signals were recorded. 3-Tesla NMR data were compared to those obtained for isometric muscular strength.</p> <p>Results</p> <p>The phosphocreatine (PCr) signal decreased robustly during ischemia and recovered rapidly during reperfusion. In contrast to PCr, the recovery of muscular strength was slow. During post-ischemic stenosis, PCr increased only slightly. The BOLD signal intensity decreased during ischemia, ischemic exercise and post-ischemic stenosis but increased during hyperemic reperfusion. IPC 4 hours prior to ischemia significantly increased the maximal PCr reperfusion signal and mitigated the peak BOLD signal during reperfusion.</p> <p>Conclusions</p> <p>Ischemic preconditioning positively influenced muscle metabolism during reperfusion; this resulted in an increase in PCr production and higher oxygen consumption, thereby mitigating the peak BOLD signal. In addition, an impairment of energy replenishment during the low-flow reperfusion was detected in this model. Thus, functional NMR is capable of characterizing changes in reperfusion and in therapeutic interventions in vivo.</p> <p>Trial Registration</p> <p>ClinicalTrials.gov: <a href="http://www.clinicaltrials.gov/ct2/show/NCT00883467">NCT00883467</a></p

Fractal-Based Analysis of Bone Microstructure in Crohn’s Disease: A Pilot Study

Crohn&rsquo;s disease (CD) is associated with bone loss and increased fracture risk. TX-Analyzer&trade; is a new fractal-based technique to evaluate bone microarchitecture based on conventional radiographs. The aim of the present study was to evaluate the TX-Analyzer&trade; of the thoracic and lumbar spine in CD patients and healthy controls (CO) and to correlate the parameters to standard imaging techniques. 39 CD patients and 39 age- and sex-matched CO were analyzed. Demographic parameters were comparable between CD and CO. Bone structure value (BSV), bone variance value (BVV) and bone entropy value (BEV) were measured at the vertebral bodies of T7 to L4 out of lateral radiographs. Bone mineral density (BMD) and trabecular bone score (TBS) by dual energy X-ray absorptiometry (DXA) were compared to TX parameters. BSV and BVV of the thoracic spine of CD were higher compared to controls, with no difference in BEV. Patients were further divided into subgroups according to the presence of a history of glucocorticoid treatment, disease duration &gt; 15 years and bowel resection. BEV was significantly lower in CD patients with these prevalent risk factors, with no differences in BMD at all sites. Additionally, TBS was reduced in patients with a history of glucocorticoid treatment. Despite a not severely pronounced bone loss in this population, impaired bone quality in CD patients with well-known risk factors for systemic bone loss was assessed by TX-Analyzer&trade;

A Randomized, First-in-Human, Healthy Volunteer Trial of sutimlimab, a Humanized Antibody for the Specific Inhibition of the Classical Complement Pathway

Aberrant activation of the classical complement pathway is the common underlying pathophysiology of orphan diseases such as bullous pemphigoid, antibodymediated rejection of organ transplants, cold agglutinin disease, and warm autoimmune hemolytic anemia. Therapeutic options for these complementmediated disorders are limited and sutimlimab, a humanized monoclonal antibody directed against complement factor C1s, may be potentially useful for inhibition of the classical complement pathway. A phase I, firstinhuman, doubleblind, randomized, placebocontrolled, doseescalation trial of single and multiple doses of sutimlimab or placebo was conducted in 64 volunteers to evaluate safety, tolerability, pharmacokinetic, and pharmacodynamic profiles. Single and multiple infusions of sutimlimab were well tolerated without any safety concerns. sutimlimab exhibited a steep concentrationeffect relationship with a Hill coefficient of 2.4, and an IC90 of 15.5 g/mL. This study establishes the foundation for using sutimlimab as a highly selective inhibitor of the classical complement pathway in different diseases.(VLID)340103