Risk factors associated with an outbreak of COVID-19 in a meat processing plant in southern Germany, April to June 2020.

Meat processing plants have been prominent hotspots for coronavirus disease (COVID-19) outbreaks around the world. We describe infection prevention measures and risk factors for infection spread at a meat processing plant in Germany with a COVID-19 outbreak from April to June 2020. We analysed a cohort of all employees and defined cases as employees with either a PCR or ELISA positive result. Of 1,270 employees, 453 (36%) had evidence of SARS-CoV-2 infection. The highest attack rates were observed in meat processing and slaughtering areas. Multivariable analysis revealed that being a subcontracted employee (adjusted risk ratio (aRR)): 1.43, 95% CI: 1.06-1.96), working in the meat cutting area (aRR: 2.44, 95% CI: 1.45-4.48), working in the slaughtering area (aRR: 2.35, 95% CI: 1.32-4.45) and being a veterinary inspector (aRR: 4.77, 95% CI: 1.16-23.68) increased infection risk. Sharing accommodation or transportation were not identified as risk factors for infection. Our results suggest that workplace was the main risk factor for infection spread. These results highlight the importance of implementing preventive measures targeting meat processing plants. Face masks, distancing, staggering breaks, increased hygiene and regular testing for SARS-CoV2 helped limit this outbreak, as the plant remained open throughout the outbreak.

Using country of origin to inform targeted tuberculosis screening in asylum seekers: a modelling study of screening data in a German federal state, 2002-2015.

BACKGROUND: Screening programmes for tuberculosis (TB) among immigrants rarely consider the heterogeneity of risk related to migrants' country of origin. We assess the performance of a large screening programme in asylum seekers by analysing (i) the difference in yield and numbers needed to screen (NNS) by country and WHO-reported TB burden, (ii) the possible impact of screening thresholds on sensitivity, and (iii) the value of WHO-estimated TB burden to improve the prediction accuracy of screening yield. METHODS: We combined individual data of 119,037 asylum seekers screened for TB in Germany (2002-2015) with TB estimates of the World Health Organization (WHO) (1990-2014) for their 81 countries of origin. Adjusted rate ratios (aRR) and 95% credible intervals (CrI) of the observed yield of screening were calculated in Bayesian Poisson regression models by categories of WHO-estimated TB incidence. We assessed changes in sensitivity depending on screening thresholds, used WHO TB estimates as prior information to predict TB in asylum seekers, and modelled country-specific probabilities of numbers needed to screen (NNS) conditional on different screening thresholds. RESULTS: The overall yield was 82 per 100,000 and the annual yield ranged from 44.1 to 279.7 per 100,000. Country-specific yields ranged from 10 (95%- CrI: 1-47) to 683 (95%-CrI: 306-1336) per 100,000 in Iraqi and Somali asylum seekers, respectively. The observed yield was higher in asylum seekers from countries with a WHO-estimated TB incidence > 50 relative to those from countries ≤50 per 100,000 (aRR: 4.17, 95%-CrI: 2.86-6.59). Introducing a threshold in the range of a WHO-estimated TB incidence of 50 and 100 per 100,000 resulted in the lowest "loss" in sensitivity. WHO's TB prevalence estimates improved prediction accuracy for eight of the 11 countries, and allowed modelling country-specific probabilities of NNS. CONCLUSIONS: WHO's TB data can inform the estimation of screening yield and thus be used to improve screening efficiency in asylum seekers. This may help to develop more targeted screening strategies by reducing uncertainty in estimates of expected country-specific yield, and identify thresholds with lowest loss in sensitivity. Further modelling studies are needed which combine clinical, diagnostic and country-specific parameters.

Yield of active screening for tuberculosis among asylum seekers in Germany: a systematic review and meta-analysis.

All asylum seekers in Germany undergo upon-entry screening for tuberculosis TB, but comprehensive evidence on the yield is lacking. We compared the national estimates with the international literature in a systematic review and meta-analysis of studies reporting the yield of TB, defined as the fraction of active TB cases detected among asylum seekers screened in Germany upon entry. We searched 11 national and international databases for empirical studies and the internet for grey literature published in English or German without restrictions on publication time. Among 1,253 screened articles, we identified six articles reporting the yield of active TB based on German data, ranging from 0.72 (95% confidence interval (CI): 0.45-1.10) to 6.41 (95% CI: 4.19-9.37) per 1,000 asylum seekers. The pooled estimate across all studies was 3.47 (95% CI: 1.78-5.73; I2 = 94.9%; p < 0.0001) per 1,000 asylum seekers. This estimate was in line with international evidence (I2 = 0%; p for heterogeneity 0.55). The meta-analysis of available international estimates resulted in a pooled yield of 3.04 (95% CI: 2.24-3.96) per 1,000. This study provides an estimate across several German federal states for the yield of TB screening in asylum seekers. Further research is needed to develop more targeted screening programmes.

An RNAi screening platform to identify secretion machinery in mammalian cells.

Integrative approaches to study protein function in a cellular context are a vital aspect of understanding human disease. Genome sequencing projects provide the basic catalogue of information with which to unravel gene function, but more systematic applications of this resource are now necessary. Here, we describe and test a platform with which it is possible to rapidly use RNA interference in cultured mammalian cells to probe for proteins involved in constitutive protein secretion. Synthetic small interfering RNA molecules are arrayed in chambered slides, then incubated with cells and an assay for secretion performed. Automated microscopy is used to acquire images from the experiments, and automated single-cell analysis rapidly provides reliable quantitative data. In test arrays of 92 siRNA spots targeting 37 prospective membrane traffic proteins, our approach identifies 7 of these as being important for the correct delivery of a secretion marker to the cell surface. Correlating these findings with other screens and bioinformatic information makes these candidates highly likely to be novel membrane traffic machinery components.

Genome-wide RNAi screening identifies human proteins with a regulatory function in the early secretory pathway.

The secretory pathway in mammalian cells has evolved to facilitate the transfer of cargo molecules to internal and cell surface membranes. Use of automated microscopy-based genome-wide RNA interference screens in cultured human cells allowed us to identify 554 proteins influencing secretion. Cloning, fluorescent-tagging and subcellular localization analysis of 179 of these proteins revealed that more than two-thirds localize to either the cytoplasm or membranes of the secretory and endocytic pathways. The depletion of 143 of them resulted in perturbations in the organization of the COPII and/or COPI vesicular coat complexes of the early secretory pathway, or the morphology of the Golgi complex. Network analyses revealed a so far unappreciated link between early secretory pathway function, small GTP-binding protein regulation, actin cytoskeleton organization and EGF-receptor-mediated signalling. This work provides an important resource for an integrative understanding of global cellular organization and regulation of the secretory pathway in mammalian cells.

Mutations affecting the secretory COPII coat component SEC23B cause congenital dyserythropoietic anemia type II.

Congenital dyserythropoietic anemias (CDAs) are phenotypically and genotypically heterogeneous diseases. CDA type II (CDAII) is the most frequent CDA. It is characterized by ineffective erythropoiesis and by the presence of bi- and multinucleated erythroblasts in bone marrow, with nuclei of equal size and DNA content, suggesting a cytokinesis disturbance. Other features of the peripheral red blood cells are protein and lipid dysglycosylation and endoplasmic reticulum double-membrane remnants. Development of other hematopoietic lineages is normal. Individuals with CDAII show progressive splenomegaly, gallstones and iron overload potentially with liver cirrhosis or cardiac failure. Here we show that the gene encoding the secretory COPII component SEC23B is mutated in CDAII. Short hairpin RNA (shRNA)-mediated suppression of SEC23B expression recapitulates the cytokinesis defect. Knockdown of zebrafish sec23b also leads to aberrant erythrocyte development. Our results provide in vivo evidence for SEC23B selectivity in erythroid differentiation and show that SEC23A and SEC23B, although highly related paralogous secretory COPII components, are nonredundant in erythrocyte maturation.