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Patients with acute myeloid leukemia (AML) are often exposed to broad-spectrum antibiotics and thus at high risk of Clostridioides difficile infections (CDI). As bacterial infections are a common cause for treatment-related mortality in these patients, we conducted a retrospective study to analyze the incidence of CDI and to evaluate risk factors for CDI in a large uniformly treated AML cohort. A total of 415 AML patients undergoing intensive induction chemotherapy between 2007 and 2019 were included in this retrospective analysis. Patients presenting with diarrhea and positive stool testing for toxin-producing Clostridioides difficile were defined to have CDI. CDI was diagnosed in 37 (8.9%) of 415 AML patients with decreasing CDI rates between 2013 and 2019 versus 2007 to 2012. Days with fever, exposition to carbapenems, and glycopeptides were significantly associated with CDI in AML patients. Clinical endpoints such as length of hospital stay, admission to ICU, response rates, and survival were not adversely affected. We identified febrile episodes and exposition to carbapenems and glycopeptides as risk factors for CDI in AML patients undergoing induction chemotherapy, thereby highlighting the importance of interdisciplinary antibiotic stewardship programs guiding treatment strategies in AML patients with infectious complications to carefully balance risks and benefits of anti-infective agents.
Purpose: The Masquelet technique for the treatment of large bone defects is a two-stage procedure based on an induced membrane. Compared to mature periosteum, the induced membrane differs significantly. However, both play a crucial role in bone regeneration. As part of a histological and radiological post-evaluation of an earlier project, we analyzed the influence of the granule size of the bone void filler Herafill® on development of periosteum regrowth in a critical size defect.
Methods: We compared three different sizes of Herafill® granules (Heraeus Medical GmbH, Wehrheim) in vivo in a rat femoral critical size defect (10 mm) treated with the induced membrane technique. After 8 weeks healing time, femurs were harvested and taken for histological and radiological analysis.
Results: A significantly increased regrowth of periosteum into the defect was found when small granules were used. Large granules showed significantly increased occurrence of bone capping. Small granules lead to significant increase in callus formation in the vicinity to the membrane.
Conclusion: The size of Herafill® granules has significant impact on the development of periosteal-like structures around the defect using Masquelet’s induced membrane technique. Small granules show significantly increased regrowth of periosteum and improved bone formation adjacent to the induced membrane.
Enhanced LTP of population spikes in the dentate gyrus of mice haploinsufficient for neurobeachin
(2020)
Deletion of the autism candidate molecule neurobeachin (Nbea), a large PH-BEACH-domain containing neuronal protein, has been shown to affect synaptic function by interfering with neurotransmitter receptor targeting and dendritic spine formation. Previous analysis of mice lacking one allele of the Nbea gene identified impaired spatial learning and memory in addition to altered autism-related behaviours. However, no functional data from living heterozygous Nbea mice (Nbea+/−) are available to corroborate the behavioural phenotype. Here, we explored the consequences of Nbea haploinsufficiency on excitation/inhibition balance and synaptic plasticity in the intact hippocampal dentate gyrus of Nbea+/− animals in vivo by electrophysiological recordings. Based on field potential recordings, we show that Nbea+/− mice display enhanced LTP of the granule cell population spike, but no differences in basal synaptic transmission, synapse numbers, short-term plasticity, or network inhibition. These data indicate that Nbea haploinsufficiency causes remarkably specific alterations to granule cell excitability in vivo, which may contribute to the behavioural abnormalities in Nbea+/− mice and to related symptoms in patients.
Individual differences in perception are widespread. Considering inter-individual variability, synesthetes experience stable additional sensations; schizophrenia patients suffer perceptual deficits in, eg, perceptual organization (alongside hallucinations and delusions). Is there a unifying principle explaining inter-individual variability in perception? There is good reason to believe perceptual experience results from inferential processes whereby sensory evidence is weighted by prior knowledge about the world. Perceptual variability may result from different precision weighting of sensory evidence and prior knowledge. We tested this hypothesis by comparing visibility thresholds in a perceptual hysteresis task across medicated schizophrenia patients (N = 20), synesthetes (N = 20), and controls (N = 26). Participants rated the subjective visibility of stimuli embedded in noise while we parametrically manipulated the availability of sensory evidence. Additionally, precise long-term priors in synesthetes were leveraged by presenting either synesthesia-inducing or neutral stimuli. Schizophrenia patients showed increased visibility thresholds, consistent with overreliance on sensory evidence. In contrast, synesthetes exhibited lowered thresholds exclusively for synesthesia-inducing stimuli suggesting high-precision long-term priors. Additionally, in both synesthetes and schizophrenia patients explicit, short-term priors—introduced during the hysteresis experiment—lowered thresholds but did not normalize perception. Our results imply that perceptual variability might result from differences in the precision afforded to prior beliefs and sensory evidence, respectively.
Background Reward processing has been proposed to underpin atypical social behavior, a core feature of autism spectrum disorder (ASD). However, previous neuroimaging studies have yielded inconsistent results regarding the specificity of atypicalities for social rewards in ASD. Utilizing a large sample, we aimed to assess altered reward processing in response to reward type (social, monetary) and reward phase (anticipation, delivery) in ASD.
Methods Functional magnetic resonance imaging during social and monetary reward anticipation and delivery was performed in 212 individuals with ASD (7.6-30.5 years) and 181 typically developing (TD) participants (7.6-30.8 years).
Results Across social and monetary reward anticipation, whole-brain analyses (p<0.05, family-wise error-corrected) showed hypoactivation of the right ventral striatum (VS) in ASD. Further, region of interest (ROI) analysis across both reward types yielded hypoactivation in ASD in both the left and right VS. Across delivery of social and monetary reward, hyperactivation of the VS in individuals with ASD did not survive correction for multiple comparisons. Reward type by diagnostic group interactions, and a dimensional analysis of autism trait scores were not significant during anticipation or delivery. Levels of attention-deficit/hyperactivity disorder (ADHD) symptoms did not affect reward processing in ASD.
Conclusions Our results do not support current theories linking atypical social interaction in ASD to specific alterations in processing of social rewards. Instead, they point towards a generalized hypoactivity of VS in ASD during anticipation of both social and monetary rewards. We suggest that this indicates attenuated subjective reward value in ASD independent of social content and ADHD symptoms.
Background: Autism Spectrum Disorder (henceforth ‘autism’) is a highly heterogeneous neurodevelopmental condition with few effective treatments for core and associated features. To make progress we need to both identify and validate neural markers that help to parse heterogeneity to tailor therapies to specific neurobiological profiles. Atypical hemispheric lateralization is a stable feature across studies in autism, however its potential of lateralization as a neural stratification marker has not been widely examined.
Methods: In order to dissect heterogeneity in lateralization in autism, we used the large EU-AIMS Longitudinal European Autism Project dataset comprising 352 individuals with autism and 233 neurotypical (NT) controls as well as a replication dataset from ABIDE (513 autism, 691 NT) using a promising approach that moves beyond mean-group comparisons. We derived grey matter voxelwise laterality values for each subject and modelled individual deviations from the normative pattern of brain laterality across age using normative modeling.
Results: Results showed that individuals with autism had highly individualized patterns of both extreme right- and leftward deviations, particularly in language-, motor- and visuospatial regions, associated with symptom severity. Language delay (LD) explained most variance in extreme rightward patterns, whereas core autism symptom severity explained most variance in extreme leftward patterns. Follow-up analyses showed that a stepwise pattern emerged with individuals with autism with LD showing more pronounced rightward deviations than autism individuals without LD.
Conclusion: Our analyses corroborate the need for novel (dimensional) approaches to delineate the heterogeneous neuroanatomy in autism, and indicate atypical lateralization may constitute a neurophenotype for clinically meaningful stratification in autism.
Background: Marked sex differences in autism prevalence accentuate the need to understand the role of biological sex-related factors in autism. Efforts to unravel sex differences in the brain organization of autism have, however, been challenged by the limited availability of female data.
Methods: We addressed this gap by using a large sample of males and females with autism and neurotypical (NT) control individuals (ABIDE; Autism: 362 males, 82 females; NT: 409 males, 166 females; 7-18 years). Discovery analyses examined main effects of diagnosis, sex and their interaction across five resting-state fMRI (R-fMRI) metrics (voxel-level Z > 3.1, cluster-level P < 0.01, gaussian random field corrected). Secondary analyses assessed the robustness of the results to different pre-processing approaches and their replicability in two independent samples: the EU-AIMS Longitudinal European Autism Project (LEAP) and the Gender Explorations of Neurogenetics and Development to Advance Autism Research (GENDAAR).
Results: Discovery analyses in ABIDE revealed significant main effects across the intrinsic functional connectivity (iFC) of the posterior cingulate cortex, regional homogeneity and voxel-mirrored homotopic connectivity (VMHC) in several cortical regions, largely converging in the default network midline. Sex-by-diagnosis interactions were confined to the dorsolateral occipital cortex, with reduced VMHC in females with autism. All findings were robust to different pre-processing steps. Replicability in independent samples varied by R-fMRI measures and effects with the targeted sex-by-diagnosis interaction being replicated in the larger of the two replication samples – EU-AIMS LEAP.
Limitations: Given the lack of a priori harmonization among the discovery and replication datasets available to date, sample-related variation remained and may have affected replicability.
Conclusions: Atypical cross-hemispheric interactions are neurobiologically relevant to autism. They likely result from the combination of sex-dependent and sex-independent factors with a differential effect across functional cortical networks. Systematic assessments of the factors contributing to replicability are needed and necessitate coordinated large-scale data collection across studies.
Competing Interest Statement: ADM receives royalties from the publication of the Italian version of the Social Responsiveness Scale Child Version by Organization Speciali, Italy. JKB has been a consultant to, advisory board member of, and a speaker for Takeda/Shire, Medice, Roche, and Servier. He is not an employee of any of these companies and not a stock shareholder of any of these companies. He has no other financial or material support, including expert testimony, patents, or royalties. CFB is director and shareholder in SBGneuro Ltd. TC has received consultancy from Roche and Servier and received book royalties from Guildford Press and Sage. DM has been a consultant to, and advisory board member, for Roche and Servier. He is not an employee of any of these companies, and not a stock shareholder of any of these companies. TB served in an advisory or consultancy role for Lundbeck, Medice, Neurim Pharmaceuticals, Oberberg GmbH, Shire, and Infectopharm. He received conference support or speakers fee by Lilly, Medice, and Shire. He received royalties from Hogrefe, Kohlhammer, CIP Medien, Oxford University Press; the present work is unrelated to these relationships. JT is a consultant to Roche. The remaining authors declare no competing interests.
Individual differences in perception are widespread. Considering inter-individual variability, synesthetes experience stable additional sensations; schizophrenia patients suffer perceptual deficits in e.g. perceptual organization (alongside hallucinations and delusions). Is there a unifying principle explaining inter-individual variability in perception? There is good reason to believe perceptual experience results from inferential processes whereby sensory evidence is weighted by prior knowledge about the world. Different perceptual phenotypes may result from different precision weighting of sensory evidence and prior knowledge. We tested this hypothesis by comparing visibility thresholds in a perceptual hysteresis task across medicated schizophrenia patients, synesthetes, and controls. Participants rated the subjective visibility of stimuli embedded in noise while we parametrically manipulated the availability of sensory evidence. Additionally, precise long-term priors in synesthetes were leveraged by presenting either synesthesia-inducing or neutral stimuli. Schizophrenia patients showed increased visibility thresholds, consistent with overreliance on sensory evidence. In contrast, synesthetes exhibited lowered thresholds exclusively for synesthesia-inducing stimuli suggesting high-precision long-term priors. Additionally, in both synesthetes and schizophrenia patients explicit, short-term priors – introduced during the hysteresis experiment – lowered thresholds but did not normalize perception. Our results imply that distinct perceptual phenotypes might result from differences in the precision afforded to prior beliefs and sensory evidence, respectively.
Successful consolidation of associative memories relies on the coordinated interplay of slow oscillations and sleep spindles during non-rapid eye movement (NREM) sleep. This enables the transfer of labile information from the hippocampus to permanent memory stores in the neocortex. During senescence, the decline of the structural and functional integrity of the hippocampus and neocortical regions is paralleled by changes of the physiological events that stabilize and enhance associative memories during NREM sleep. However, the currently available evidence is inconclusive as to whether and under which circumstances memory consolidation is impacted during aging. To approach this question, 30 younger adults (19–28 years) and 36 older adults (63–74 years) completed a memory task based on scene–word associations. By tracing the encoding quality of participants’ individual memory associations, we demonstrate that previous learning determines the extent of age-related impairments in memory consolidation. Specifically, the detrimental effects of aging on memory maintenance were greatest for mnemonic contents of intermediate encoding quality, whereas memory gain of poorly encoded memories did not differ by age. Ambulatory polysomnography (PSG) and structural magnetic resonance imaging (MRI) data were acquired to extract potential predictors of memory consolidation from each participant’s NREM sleep physiology and brain structure. Partial Least Squares Correlation was used to identify profiles of interdependent alterations in sleep physiology and brain structure that are characteristic for increasing age. Across age groups, both the ‘aged’ sleep profile, defined by decreased slow-wave activity (0.5–4.5 Hz), and a reduced presence of slow oscillations (0.5–1 Hz), slow, and fast spindles (9–12.5 Hz; 12.5–16 Hz), as well as the ‘aged’ brain structure profile, characterized by gray matter reductions in the medial prefrontal cortex, thalamus, entorhinal cortex, and hippocampus, were associated with reduced memory maintenance. However, inter-individual differences in neither sleep nor structural brain integrity alone qualified as the driving force behind age differences in sleep-dependent consolidation in the present study. Our results underscore the need for novel and age-fair analytic tools to provide a mechanistic understanding of age differences in memory consolidation.
We studied oscillatory mechanisms of memory formation in 48 younger and 51 older adults in an intentional associative memory task with cued recall. While older adults showed lower memory performance than young adults, we found subsequent memory effects (SME) in alpha/beta and theta frequency bands in both age groups. Using logistic mixed effects models, we investigated whether interindividual differences in structural integrity of key memory regions could account for interindividual differences in the strength of the SME. Structural integrity of inferior frontal gyrus (IFG) and hippocampus was reduced in older adults. SME in the alpha/beta band were modulated by the cortical thickness of IFG, in line with its hypothesized role for deep semantic elaboration. Importantly, this structure–function relationship did not differ by age group. However, older adults were more frequently represented among the participants with low cortical thickness and consequently weaker SME in the alpha band. Thus, our results suggest that differences in the structural integrity of the IFG contribute not only to interindividual, but also to age differences in memory formation.
Based on Eysenck’s pioneering work, CNS arousal has long been considered an encouraging biological candidate that may explain individual differences in human personality. Yet, results from empirical studies remained inconclusive. Notably, the vast majority of published results have been derived from small samples, and EEG alpha power has usually served as exclusive indicator for CNS arousal. In this study, we selected N = 468 individuals of the LIFE-Adult cohort and investigated the associations between the Big Five personality traits and CNS arousal by using the low-resolution electromagnetic tomography-based analysis tool VIGALL. Our analyses revealed that subjects who reported higher levels of extraversion and openness to experience, respectively, exhibited lower levels of CNS arousal in the resting state. Bayesian and frequentist analysis results were especially convincing for openness to experience. Among the lower-order personality traits, we obtained strongest evidence for neuroticism facet ‘impulsivity’ and reduced CNS arousal. We regard these findings as well in line with the postulations of Eysenck and Zuckerman and consistent with the assumptions of the ‘arousal regulation model’. Our results also agree with meta-analytically derived effect sizes in the field of individual differences research, highlighting the need for large studies with at least several hundreds of subjects.
Introduction: In recent years, resource-saving handling of allogeneic blood products and a reduction of transfusion rates in adults has been observed. However, comparable published national data for transfusion practices in pediatric patients are currently not available. In this study, the transfusion rates for children and adolescents were analyzed based on data from the Federal Statistical Office of Germany during the past 2 decades. Methods: Data were queried via the database of the Federal Statistical Office (Destasis). The period covered was from 2005 to 2018, and those in the sample group were children and adolescents aged 0–17 years receiving inpatient care. Operation and procedure codes (OPS) for transfusions, procedures, or interventions with increased transfusion risk were queried and evaluated in detail. Results: In Germany, 0.9% of the children and adolescents treated in hospital received a transfusion in 2018. A reduction in transfusion rates from 1.02% (2005) to 0.9% (2018) was observed for the total collective of children and adolescents receiving inpatient care. Increases in transfusion rates were recorded for 1- to 4- (1.41–1.45%) and 5- to 10-year-olds (1.24–1.33%). Children under 1 year of age were most frequently transfused (in 2018, 40.2% of the children were cared for in hospital). Transfusion-associated procedures such as chemotherapy or machine ventilation and respiratory support for newborns and infants are on the rise. Conclusion: Transfusion rates are declining in children and adolescents, but the reasons for increases in transfusion rates in other groups are unclear. Prospective studies to evaluate transfusion rates and triggers in children are urgently needed.
Background: Plasma transfusions are most commonly used therapeutically for bleeding or prophylactically in non-bleeding patients prior to invasive procedures or surgery. Although plasma transfusions generally seem to decline, plasma usage for indications that lack evidence of efficacy prevail. Summary: There is wide international, interinstitutional, and interindividual variance regarding the compliance with guidelines based on published references, supported by appropriate testing. There is furthermore a profound lack of evidence from randomized controlled trials comparing the effect of plasma transfusion with that of other therapeutic interventions for most indications, including massive bleeding. The expected benefit of a plasma transfusion needs to be balanced carefully against the associated risk of adverse events. In light of the heterogeneous nature of bleeding conditions and their rapid evolvement over time, fibrinogen and factor concentrate therapy, directed at specific phases of coagulation identified by alternative laboratory assays, may offer advantages over conventional blood product ratio-driven resuscitation. However, their outcome benefit has not been demonstrated in well-powered prospective trials. This systematic review will detail the current evidence base for plasma transfusion in adult surgical patients.
Management of decompensated cirrhosis is currently geared towards the treatment of complications once they occur. To date there is no established disease-modifying therapy aimed at halting progression of the disease and preventing the development of complications in patients with decompensated cirrhosis. The design of clinical trials to investigate new therapies for patients with decompensated cirrhosis is complex. The population of patients with decompensated cirrhosis is heterogeneous (i.e., different etiologies, comorbidities and disease severity), leading to the inclusion of diverse populations in clinical trials. In addition, primary endpoints selected for trials that include patients with decompensated cirrhosis are not homogeneous and at times may not be appropriate. This leads to difficulties in comparing results obtained from different trials. Against this background, the LiverHope Consortium organized a meeting of experts, the goal of which was to develop recommendations for the design of clinical trials and to define appropriate endpoints, both for trials aimed at modifying the natural history and preventing progression of decompensated cirrhosis, as well as for trials aimed at managing the individual complications of cirrhosis.
Functional genomics studies in model organisms and human cell lines provided important insights into gene functions and their context-dependent role in genetic circuits. However, our functional understanding of many of these genes and how they combinatorically regulate key biological processes, remains limited. To enable the SpCas9-dependent mapping of gene-gene interactions in human cells, we established 3Cs multiplexing for the generation of combinatorial gRNA libraries in a distribution-unbiased manner and demonstrate its robust performance. The optimal number for combinatorial hit calling was 16 gRNA pairs and the skew of a library’s distribution was identified as a critical parameter dictating experimental scale and data quality. Our approach enabled us to investigate 247,032 gRNA-pairs targeting 12,736 gene-interactions in human autophagy. We identified novel genes essential for autophagy and provide experimental evidence that gene-associated categories of phenotypic strengths exist in autophagy. Furthermore, circuits of autophagy gene interactions reveal redundant nodes driven by paralog genes. Our combinatorial 3Cs approach is broadly suitable to investigate unexpected gene-interaction phenotypes in unperturbed and diseased cell contexts.
While the liver, specifically hepatocytes, are widely accepted as the main source for hepatitis C virus (HCV) production, the role of the liver/hepatocytes in the clearance of circulating HCV remains largely unknown. Here we evaluated the function of the liver/hepatocytes in clearing virus from the circulation by investigating viral clearance during liver transplantation and from culture medium in vitro. Frequent HCV kinetic data during liver transplantation were recorded from 5 individuals throughout the anhepatic (AH) phase and for 4 hours after reperfusion (RP), along with recordings of fluid balances. Using mathematical modeling, the serum viral clearance rate, c, was estimated. Analogously, we monitored the clearance rate of HCV at 37°C from culture medium in vitro in the absence and presence of chronically infected Huh7 human hepatoma cells. During the AH phase, in 3 transplant cases viral levels remained at pre-AH levels, while in the other 2 cases HCV declined (half-life, t1/2~1h). Immediately post-RP, virus declined in a biphasic manner in Cases 1-4 consisting of an extremely rapid (median t1/2=5min) decline followed by a slower decline (HCV t1/2=67min). In Case 5, HCV remained at the same level post-RP as at the end of AH. Declines in virus level were not explained by adjusting for dilution from IV fluid and blood products. Consistent with what was observed in the majority of patients in the anhepatic phase, the t1/2 of HCV in cell culture was much longer in the absence of chronically HCV-infected Huh7 cells. Therefore, kinetic and modeling results from both in vivo liver transplantation cases and in vitro cell culture studies suggest that the liver plays a major role in clearing HCV from the circulation.
SARS-CoV-2 and stroke characteristics: a report from the Multinational COVID-19 Stroke Study Group
(2020)
Background: Stroke is reported as a consequence of SARS-CoV-2 infection. However, there is a lack of regarding comprehensive stroke phenotype and characteristics
Methods: We conducted a multinational observational study on features of consecutive acute ischemic stroke (AIS), intracranial hemorrhage (ICH), and cerebral venous or sinus thrombosis (CVST) among SARS-CoV-2 infected patients. We further investigated the association of demographics, clinical data, geographical regions, and countries’ health expenditure among AIS patients with the risk of large vessel occlusion (LVO), stroke severity as measured by National Institute of Health stroke scale (NIHSS), and stroke subtype as measured by the TOAST criteria. Additionally, we applied unsupervised machine learning algorithms to uncover possible similarities among stroke patients.
Results: Among the 136 tertiary centers of 32 countries who participated in this study, 71 centers from 17 countries had at least one eligible stroke patient. Out of 432 patients included, 323(74.8%) had AIS, 91(21.1%) ICH, and 18(4.2%) CVST. Among 23 patients with subarachnoid hemorrhage, 16(69.5%) had no evidence of aneurysm. A total of 183(42.4%) patients were women, 104(24.1%) patients were younger than 55 years, and 105(24.4%) patients had no identifiable vascular risk factors. Among 380 patients who had known interval onset of the SARS-CoV-2 and stroke, 144(37.8%) presented to the hospital with chief complaints of stroke-related symptoms, with asymptomatic or undiagnosed SARS-CoV-2 infection. Among AIS patients 44.5% had LVO; 10% had small artery occlusion according to the TOAST criteria. We observed a lower median NIHSS (8[3-17], versus 11 [5-17]; p=0.02) and higher rate of mechanical thrombectomy (12.4% versus 2%; p<0.001) in countries with middle to high-health expenditure when compared to countries with lower health expenditure. The unsupervised machine learning identified 4 subgroups, with a relatively large group with no or limited comorbidities.
Conclusions: We observed a relatively high number of young, and asymptomatic SARS-CoV-2 infections among stroke patients. Traditional vascular risk factors were absent among a relatively large cohort of patients. Among hospitalized patients, the stroke severity was lower and rate of mechanical thrombectomy was higher among countries with middle to high-health expenditure.
Background Stigma has been considered a significant barrier both in treatment, rehabilitation and help-seeking behaviours of people diagnosed with depression. This study aimed to assess the influence of the type of previous experience with depression on depression stigma, identify the effects of previous experience with depression on stigma and to analyse the effects of stigma on help-seeking attitudes.
Methods A total of 1693 participants with a mean age of 47.2 (SD=18.17) completed the Depression Stigma Scale (DSS), the Attitude Toward Seeking Professional Psychological Help (ATSPPH), and a sociodemographic questionnaire. We categorised participants into four comparison groups: no previous experience with depression (n=479), indirect experience with depression (n=661), direct experience with depression (n=137), and both direct and indirect experience with depression (n=416). Data were analysed using SPSS 24.0.
Results Levels of personal stigma were lower in people who had family and friends experiencing depression in comparison with individuals with no history of depression experience. Better attitudes towards help-seeking were evident in those with lower personal stigma, and worse help-seeking attitudes were associated with higher perceived stigma in the indirect previous experience group.
Limitations Duration of participant exposure to depression was not collected.
Conclusions The individual’s experience with depression influences the development of personal stigmatisation towards depression and plays a role in help-seeking behaviours. Addressing people’s experience of depression might be a practical way of reducing depression stigma and improve help-seeking behaviours.
Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) can spread from symptomatic patients with COVID-19, but also from asymptomatic individuals. Therefore, robust surveillance and timely interventions are essential for the control of virus spread within the community. In this regard the frequency of testing and speed of reporting, but not the test sensitivity alone, play a crucial role. In order to reduce the costs and meet the expanding demands in real-time RT-PCR (rRT-PCR) testing for SARS-CoV-2, complementary assays, such as rapid antigen tests, have been developed. Rigorous analysis under varying conditions is required to assess the clinical performance of these tests and to ensure reproducible results. We evaluated the sensitivity and specificity of a recently licensed rapid antigen test using 137 clinical samples in two institutions. Test sensitivity was between 88.2-89.6% when applied to samples with viral loads typically seen in infectious patients. Of 32 rRT-PCR positive samples, 19 demonstrated infectivity in cell culture, and 84% of these samples were reactive with the antigen test. Seven full-genome sequenced SARS-CoV-2 isolates and SARS-CoV-1 were detected with this antigen test, with no cross-reactivity against other common respiratory viruses. Numerous antigen tests are available for SARS-CoV-2 testing and their performance to detect infectious individuals may vary. Head-to-head comparison along with cell culture testing for infectivity may prove useful to identify better performing antigen tests. The antigen test analyzed in this study is easy-to-use, inexpensive, and scalable. It can be helpful in monitoring infection trends and thus has potential to reduce transmission.
The novel coronavirus (SARS-CoV-2), identified in China at the end of December 2019 and causing the disease COVID-19, has meanwhile led to outbreaks all over the globe, with about 571,700 confirmed cases and about 26,500 deaths as of March 28th, 2020. We present here the preliminary results of a mathematical study directed at informing on the possible application or lifting of control measures in Germany. The developed mathematical models allow to study the spread of COVID-19 among the population in Germany and to asses the impact of non-pharmaceutical interventions.