Mpox outbreak 2022: an overview of all cases reported to the Cologne Health Department.

PURPOSE: The worldwide mpox outbreak starting in May 2022 marks the occurrence of another previously atypical infectious disease in Europe. This study's objective was to present a comprehensive overview based on the gathered data and to illustrate the approach of the Cologne Health Department to contain the mpox outbreak. METHODS: In this retrospective observational study, 368 individuals reported to the Cologne Health Department as PCR-positive for mpox were included. Data were collected in structured telephone interviews and digitally processed. RESULTS: The first mpox case in Cologne was recorded on May 24, 2022. The local outbreak lasted approximately 4 months and reached its peak in July. The last reported case in Cologne occurred on September 17. Transmissions mostly occurred through sexual contacts (67.4%) or other close physical contacts (4.6%) between men, but also through fomites, in the context of events or occasionally in the work environment. In 21.5% of cases, no route of infection could be determined. The mean incubation period was 8.2 days. Clinically, mpox infections usually presented with skin and/or mucosal lesions accompanied by general symptoms. In 74.8% of cases, a prodromal stage was absent. Initially, the rash often had an unspecific appearance, but in the further clinical course, it usually passed through the typical stages. Most infections resolved spontaneously under home care. In 3.5% of cases, however, inpatient hospitalisation was required. Infected persons with a previous smallpox vaccination had 0.43 times the odds of unvaccinated persons to be affected by lesions in 3 or more body regions and 0.30 times the odds to develop lesions in all 5 body regions. Previous vaccination statistically reduced the total duration of symptoms by 2.0 days. CONCLUSIONS: The mpox outbreak 2022 in Cologne primarily affected men who have sex with men and have reported recent sexual encounters. The observed average incubation period was shorter than initially assumed. Mucosal involvement and associated symptoms occur in a relevant number of cases and can lead to more severe clinical courses. Previous smallpox vaccination was statistically significantly associated with milder courses of mpox. In the case of an unclear rash or symptoms suggesting mucosal involvement, mpox should be considered as a differential diagnosis. An equally rapid and well-orchestrated public health response are crucial for infection control.

Refining animal research: The Animal Study Registry.

The Animal Study Registry (ASR; www.animalstudyregistry.org) was launched in January 2019 for preregistration of animal studies in order to increase transparency and reproducibility of bioscience research and to promote animal welfare. The registry is free of charge and is designed for exploratory and confirmatory studies within applied science as well as basic and preclinical research. The registration form helps scientists plan their study thoroughly by asking detailed questions concerning study design, methods, and statistics. With registration, the study automatically receives a digital object identifier (DOI) that marks it as intellectual property of the researcher. To accommodate the researchers concerns about theft of ideas, users can restrict the visibility of their registered studies for up to 5 years. The full content of the study becomes publicly accessible at the end of the embargo period. Because the platform is embedded in the infrastructure of the German Federal Government, continuity and data security are provided. By registering a study in the ASR, researchers can show their commitment to transparency and data quality to reviewers and editors, to third-party donors, and to the general public.

Rethinking the incentive system in science: animal study registries: Preregistering experiments using animals could greatly improve transparency and reliability of biomedical studies and improve animal welfare.

The Animal Study Registry offers scientists a range of benefits by preregistering their studies. Wider adoption could address the reproducibility problem in biomedical research and enhance animal welfare.

Rethinking 3R strategies: Digging deeper into AnimalTestInfo promotes transparency in in vivo biomedical research.

In the European Union (EU), animal welfare is seen as a matter of great importance. However, with respect to animal experimentation, European citizens feel quite uninformed. The European Directive 2010/63/EU for the protection of laboratory animals aims for greater transparency and requires that a comprehensible, nontechnical summary (NTS) of each authorised research project involving animals is published by the respective Member State. However, the NTSs remain sleeping beauties if their contents are not easily and systematically accessible. The German web-based NTS database AnimalTestInfo is a unique channel for scientists to communicate their work, and provides the opportunity for large-scale analyses of planned animal studies to inform researchers and the public. For an in-depth meta-analysis, we classified the duly completed NTSs submitted to AnimalTestInfo in 2014 and 2015 according to the International Classification of Diseases and Related Health Problems (ICD) system. Indexing the NTSs with ICD codes provided a fine-grained overview of the prospective uses of experimental animals. Using this approach, transparency, especially for highly controversial animal research involving, for example, nonhuman primates, is fostered, as it enables pinpointing the envisaged beneficiary down to the level of the addressed disease. Moreover, research areas with many planned projects involving animals can be specified in detail. The development of 3R (replacement, reduction, and refinement) measures in these research areas may be most efficient, as a large number of experimental animals would benefit from it. Indexing NTSs with ICD codes can support governments and funding agencies in advancing target-oriented funding of 3R research. Data drawn from NTSs can provide a basis for the development, validation, and implementation of directed 3R strategies as well as guidance for rethinking the role of animal research models.

Correction: Where is the greatest risk of COVID-19 infection? Findings from Germany's largest public health department, Cologne.

[This corrects the article DOI: 10.1371/journal.pone.0273496.].

Self-Reported Pre-Pandemic Physical Activity and Likelihood of COVID-19 Infection: Data from the First Wave of the CoCo-Fakt Survey.

OBJECTIVES: To investigate the potential protective role of exercise on the odds of COVID-19 infection in unvaccinated contact persons (CPs) who were at higher risk of infection due to confirmed contact with infected persons. METHODS: Before the onset of the vaccination campaign, the first wave of the CoCo-Fakt online survey was conducted with SARS-CoV-2-positive persons and their confirmed contacts who were isolated/quarantined between 1 March 2020 and 9 December 2020. Within this analysis, 5338 CPs were included and divided into those who subsequently tested positive (CP-P) and those who remained negative (CP-N). We assessed demographics as well as pre-pandemic lifestyle characteristics including physical activity (PA; type, frequency, time, intensity; duration clustered as 'below PA guidelines', 'meeting PA guidelines', and 'above PA guidelines'; intensity clustered as 'low intensity' and 'moderate-to-vigorous intensity') and sedentary behaviour. RESULTS: A greater percentage of CP-Ns reported being active before the pandemic compared to CP-Ps (69% vs. 63%; p = .004). Moreover, CP-Ns reported higher PA duration (164.1 min/week vs. 143.2 min/week; p = .038) and higher PA intensities than CP-Ps (67% vs. 60% moderate-to-vigorous intensity, 33% vs. 40% low intensity; p = .003). Adjusting for age, sex, socioeconomic status, migration background, and pre-existing chronic diseases, the odds of infection were negatively associated with exercise (yes/no) (Nagelkerke R2 = 1.9%), PA levels above PA guidelines (Nagelkerke R2 = 2.0%), and PA intensity (Nagelkerke R2 = 1.8%). CONCLUSION: Due to the beneficial effects of PA on the odds of infection, an active lifestyle should be promoted especially during possible subsequent pandemics (while taking into account necessary hygiene measures). Moreover, inactive and chronically ill persons should be especially encouraged to adopt a healthier lifestyle.

Automatic classification of experimental models in biomedical literature to support searching for alternative methods to animal experiments.

Current animal protection laws require replacement of animal experiments with alternative methods, whenever such methods are suitable to reach the intended scientific objective. However, searching for alternative methods in the scientific literature is a time-consuming task that requires careful screening of an enormously large number of experimental biomedical publications. The identification of potentially relevant methods, e.g. organ or cell culture models, or computer simulations, can be supported with text mining tools specifically built for this purpose. Such tools are trained (or fine tuned) on relevant data sets labeled by human experts. We developed the GoldHamster corpus, composed of 1,600 PubMed (Medline) articles (titles and abstracts), in which we manually identified the used experimental model according to a set of eight labels, namely: "in vivo", "organs", "primary cells", "immortal cell lines", "invertebrates", "humans", "in silico" and "other" (models). We recruited 13 annotators with expertise in the biomedical domain and assigned each article to two individuals. Four additional rounds of annotation aimed at improving the quality of the annotations with disagreements in the first round. Furthermore, we conducted various machine learning experiments based on supervised learning to evaluate the corpus for our classification task. We obtained more than 7,000 document-level annotations for the above labels. After the first round of annotation, the inter-annotator agreement (kappa coefficient) varied among labels, and ranged from 0.42 (for "others") to 0.82 (for "invertebrates"), with an overall score of 0.62. All disagreements were resolved in the subsequent rounds of annotation. The best-performing machine learning experiment used the PubMedBERT pre-trained model with fine-tuning to our corpus, which gained an overall f-score of 0.83. We obtained a corpus with high agreement for all labels, and our evaluation demonstrated that our corpus is suitable for training reliable predictive models for automatic classification of biomedical literature according to the used experimental models. Our SMAFIRA - "Smart feature-based interactive" - search tool ( https://smafira.bf3r.de ) will employ this classifier for supporting the retrieval of alternative methods to animal experiments. The corpus is available for download ( https://doi.org/10.5281/zenodo.7152295 ), as well as the source code ( https://github.com/mariananeves/goldhamster ) and the model ( https://huggingface.co/SMAFIRA/goldhamster ).

Vaccination and Transmission Risk during the Outbreak of B.1.1.529 (Omicron).

Since its first description in November 2021, the SARS-CoV-2 variant of concern Omicron (B.1.1.529) has emerged as the dominant strain in the COVID-19 pandemic. To date, it remains unclear if boosted vaccination protects against transmission. Using data from the largest German Public Health Department, Cologne, we analyzed breakthrough infections in booster-vaccinated infected persons (IP; booster-vaccinated group (BVG); n = 202) and fully vaccinated, not boosted SARS-COV2-positive patients (>3 month after receiving the second dose; unboosted, fully vaccinated group (FVG); n = 202) to close contacts compared to an age- and sex-matched unvaccinated control group (UCG; n = 202). On average, IPs had 0.42 ± 0.52 infected contacts in relation to the total number of contacts in the BVG vs. 0.57 ± 0.44 in the FVG vs. 0.56 ± 0.43 in the UVG (p = 0.054). In the median test, pairwise comparison revealed a significant difference between the BVG and both other groups; no difference was found between the fully vaccinated and the unvaccinated control group. Now, these findings must be verified in larger samples, considering the role of Omicron subvariants and the vaccination status of the contact person. However, the importance of the booster vaccination in breaking possible chains of infection in the immune escape variant Omicron is obvious.

Adherence to stay-at-home orders: awareness, implementation and difficulties of officially ordered quarantine measures in the context of the COVID-19 pandemic in Cologne - a retrospective cohort study.

OBJECTIVES: To estimate the awareness, implementation and difficulty of behavioural recommendations and their correlates in officially ordered domestic isolation and quarantine during the COVID-19 pandemic. DESIGN: Online retrospective cohort survey conducted from 12 December 2020 to 6 January 2021 as part of the Cologne-Corona Counselling and Support for Index and Contact Persons During the Quarantine Period study. SETTING: Administrative area of the city of Cologne, Germany. PARTICIPANTS: 3011 infected persons (IPs) and 5822 contacts over 16 years of age who were in officially ordered domestic isolation or quarantine between 28 February 2020 and 9 December 2020. Of these, 60.4% were women. OUTCOME MEASURES: Self-developed scores were calculated based on responses about awareness and implementation of 19 behavioural recommendations to determine community-based and household-based adherence. Linear regression analyses were conducted to determine factors influencing adherence. RESULTS: The average adherence to all recommendations, including staying in a single room, keeping distance and wearing a mask, was 13.8±2.4 out of 15 points for community-based recommendations (CBRs) and 17.2±6.8 out of 25 points for household-based recommendations (HBRs). IPs were significantly more adherent to CBRs (14.3±2.0 points vs 13.7±2.6 points, p<0.001) and HBRs (18.2±6.7 points vs 16.5±6.8 points, p<0.001) than were contact persons. Among other factors, both status as an IP and being informed about the measures positively influenced participants' adherence. The linear regression analysis explained 6.6% and 14.4% (corr. R²) of the adherence to CBRs and HBRs. CONCLUSIONS: Not all persons under official quarantine were aware of the relevant behavioural recommendations. This was especially true in cases where instructions were given for measures to be taken in one's own household. Due to the high transmission rates within households, HBRs should be communicated with particular emphasis.

Impact of physical activity on COVID-19-related symptoms and perception of physical performance, fatigue and exhaustion during stay-at-home orders.

Objectives: The measures used to contain the COVID-19 pandemic led to a significant reduction in physical activity. Due to the health benefits of exercise, recommendations were made for lockdown restrictions. Within the CoCo-Fakt study (Cologne-Corona counselling and support for index and contacts during the quarantine period), we aimed to determine how these recommendations were implemented, especially by individuals who were officially quarantined due to an infected persons (IPs) or as close contacts (CPs), and how this affected their physical and psychological condition. Methods: From 12 December 2020 to 6 January 2021, all IPs and CPs registered by Cologne's public health department up to the survey period were surveyed online. Of 10 547 people in the CoCo-Fakt sample, 8102 were integrated into the current analysis. In addition to demographic data, information regarding COVID-19-specific and persistent symptoms or conditions and their association with the amount and type of exercise and screen time before and during the quarantine were collected. Results: Before quarantine, 66.9% of IPs and 69% of CPs were physically active; during quarantine, this decreased by 49.4% in IPs depending on the course of the disease and by 30.6% in CPs. Physically active IPs and CPs felt less exhausted and more fit during their quarantine periods than those who were inactive, with active IPs significantly less likely to report prolonged physical and psychological symptoms than their more sedentary counterparts. Conclusion: Given the acute and long-term positive effects of exercise on quarantined individuals, corresponding recommendations should be communicated to those affected, especially CPs. Recommendations for IPs depend on their health status.

Where is the greatest risk of COVID-19 infection? Findings from Germany's largest public health department, Cologne.

BACKGROUND: SARS-CoV-2 has been spreading worldwide since late 2019. Before vaccines became available, exclusively non-pharmaceutical measures were used to prevent transmission of infection. Despite the fact that vaccinations are now available, it is still important to identify relevant transmission routes in order to contain the COVID-19- or further pandemics. Therefore, this study aims to systematically analyse data from the largest public health department in Germany to determine the significance of the various known and unknown transmission situations in terms of the proportion of infections. METHODS: All infections in Cologne were systematically recorded by the local health department. In addition to clinical data, the transmission situations were recorded and categorised as pertaining to social contact, work contact, travellers, health care workers, users of educational institutions, visitors of community institutions, infection in the context of medical treatment, and unknown infection. FINDINGS: The analysis included 25,966 persons. A transmission situation could be identified in 82.7% of the cases (n = 21,477). Most persons (42.1%) were infected due to social contact, primarily within their own household. Another 22.3% were infected at their place of work; this was particularly common among staff members of medical facilities, nursing homes and educational institutions. In 17.3% of the cases, the transmission situation remained unknown; the cases with unknown transmission situation were slightly more often symptomatic (75.2%) than the cases with known transmission situation (69.4%). INTERPRETATION: Considering that during the study period the leading strains were the wild-type and alpha-variant transmission rather occurred during scenarios involving close contacts than in anonymous situations. Presumably, however, the findings can be transferred to the new variants. Therefore, in order to prevent transmission, besides vaccination regular antigen tests and/or appropriate protective measures remain relevant until this pandemic has subsided.

Symptom diaries as a digital tool to detect SARS-CoV-2 infections and differentiate between prevalent variants.

The COVID-19 pandemic and the high numbers of infected individuals pose major challenges for public health departments. To overcome these challenges, the health department in Cologne has developed a software called DiKoMa. This software offers the possibility to track contact and index persons, but also provides a digital symptom diary. In this work, the question of whether these can also be used for diagnostic purposes will be investigated. Machine learning makes it possible to identify infections based on early symptom profiles and to distinguish between the predominant dominant variants. Focusing on the occurrence of the symptoms in the first week, a decision tree is trained for the differentiation between contact and index persons and the prevailing dominant variants (Wildtype, Alpha, Delta, and Omicron). The model is evaluated, using sex- and age-stratified cross-validation and validated by symptom profiles of the first 6 days. The variants achieve an AUC-ROC from 0.89 for Omicron and 0.6 for Alpha. No significant differences are observed for the results of the validation set (Alpha 0.63 and Omicron 0.87). The evaluation of symptom combinations using artificial intelligence can determine the individual risk for the presence of a COVID-19 infection, allows assignment to virus variants, and can contribute to the management of epidemics and pandemics on a national and international level. It can help to reduce the number of specific tests in times of low labor capacity and could help to early identify new virus variants.

Changes in Alcohol Consumption, Eating Behaviors, and Body Weight during Quarantine Measures: Analysis of the CoCo-Fakt Study.

INTRODUCTION: Public health measures enacted to reduce COVID-19 transmission have affected individuals' lifestyles, mental health, and psychological well-being. To date, little is known how stay-at-home orders have influenced the eating behaviors, weight development, and alcohol consumption of quarantined persons. The CoCo-Fakt cohort study analyzed these parameters and their association with psychological distress and coping strategies. METHODS: An online survey was conducted of all persons who tested positive for SARS-CoV-2 (infected persons [IP]) between December 12, 2020, and January 6, 2021, as well as their close contacts (contact persons [CP]) registered by the public health department of Cologne. 8,075 of 33,699 individuals were included in the analysis. In addition to demographic data, psychological distress, and coping strategies, information on changes in body weight, eating, and drinking behaviors was collected. RESULTS: IP lost 1.2 ± 4.4 kg during the quarantine period, and CP gained 1.6 ± 4.1 kg. The reasons given by IP for weight change were mainly loss of taste and feeling sick, whereas CP were more likely than IP to eat out of boredom. Higher psychological burden and lower coping strategies were associated with both weight gain and loss. Of the 30.8% of participants who changed their alcohol consumption during the quarantine period, CP in particular drank more alcohol (IP 15.2%; CP 47.7%). Significantly less alcohol was consumed by individuals with higher coping scores. CONCLUSION: In this short but psychologically stressful period of stay-at-home orders, changes in eating and drinking behavior as well as weight development are evident, mainly in high-risk contacts. To avoid possible long-term sequelae, health authorities should take these findings into account during the quarantine period; in particular, general practitioners should consider these findings during follow-up.

Alternatives to animal testing: current status and future perspectives.

On the occasion of the 20th anniversary of the Center for Alternative Methods to Animal Experiments (ZEBET), an international symposium was held at the German Federal Institute for Risk Assessment (BfR) in Berlin. At the same time, this symposium was meant to celebrate the 50th anniversary of the publication of the book "The Principles of Humane Experimental Technique" by Russell and Burch in 1959 in which the 3Rs principle (that is, Replacement, Reduction, and Refinement) has been coined and introduced to foster the development of alternative methods to animal testing. Another topic addressed by the symposium was the new vision on "Toxicology in the twenty-first Century", as proposed by the US-National Research Council, which aims at using human cells and tissues for toxicity testing in vitro rather than live animals. An overview of the achievements and current tasks, as well as a vision of the future to be addressed by ZEBET@BfR in the years to come is outlined in the present paper.

A knowledge-based search engine to navigate the information thicket of nanotoxicology.

The risk assessment of nano-sized materials (NM) currently suffers from great uncertainties regarding their putative toxicity for humans and the environment. An extensive amount of the respective original research literature has to be evaluated before a targeted and hypothesis-driven Environmental and Health Safety research can be stipulated. Furthermore, to comply with the European animal protection legislation in vitro testing has to be preferred whenever possible. Against this background, there is the need for tools that enable producers of NM and risk assessors for a fast and comprehensive data retrieval, thereby linking the 3Rs principle to the hazard identification of NM. Here we report on the development of a knowledge-based search engine that is tailored to the particular needs of risk assessors in the area of NM. Comprehensive retrieval of data from studies utilising in vitro as well as in vivo methods relying on the PubMed database is presented exemplarily with a titanium dioxide case study. A fast, relevant and reliable information retrieval is of paramount importance for the scientific community dedicated to develop safe NM in various product areas, and for risk assessors obliged to identify data gaps, to define additional data requirements for approval of NM and to create strategies for integrated testing using alternative methods.