BACKGROUND:The World Health Organization declared the outbreak of coronavirus disease to be a public health emergency of international concern on January 30, 2020. The first SARS-CoV-2 infection was subsequently detected in Luxembourg on February 29, 2020. Representative population-based data, including asymptomatic individuals for assessing the viral spread and immune response was, however, lacking worldwide. METHODS:Using a panel-based method, we recruited a representative sample of the Luxembourgish population based on age, gender and residency for testing for SARS-CoV-2 infection and antibody status in order to define prevalence irrespective of clinical symptoms. Participants were contacted via email to fill an online questionnaire before biosampling at local laboratories. Participants provided information related to clinical symptoms, epidemiology, socioeconomic and psychological assessments and underwent biosampling, rRT-PCR testing and serology for SARS-CoV-2. RESULTS:A total of 1862 individuals were included for our representative sample of the general Luxembourgish population. We detected an ongoing SARS-CoV-2 infection based on rRT-PCR in 5 participants. h Four of the SARS-CoV-2 infected participants were oligosymptomatic and one was asymptomatic. Overall, 35 participants (1.97%) had developed a positive IgG response, of whom 11 self-reported to have previously received a positive rRT-PCR diagnosis of SARS-CoV-2 infection. Our data indicate a prevalence of 0.3% for active SARS-CoV-2 infection in the Luxembourgish population between 18 and 79 years of age. CONCLUSIONS:Luxembourgish residents show a low rate of acute infections after 7 weeks of confinement and present with an antibody profile indicative of a more recent immune response to SARS-CoV-2. All infected individuals were oligo-or asymptomatic. Bi-weekly follow-up visits over the next 2 months will inform about the viral spread by oligo-and asymptomatic carriers and the individual changes in the immune profile.

While genetic advances have successfully defined part of the complexity in Parkinson’s disease (PD), the clinical characterization of phenotypes remains challenging. Therapeutic trials and cohort studies typically include patients with earlier disease stages and exclude comorbidities, thus ignoring a substantial part of the real-world PD population. To account for these limitations, we implemented the Luxembourg PD study as a comprehensive clinical, molecular and device-based approach including patients with typical PD and atypical parkinsonism, irrespective of their disease stage, age, comorbidities, or linguistic background. To provide a large, longitudinally followed, and deeply phenotyped set of patients and controls for clinical and fundamental research on PD, we implemented an open-source digital platform that can be harmonized with international PD cohort studies. Our interests also reflect Luxembourg-specific areas of PD research, including vision, gait, and cognition. This effort is flanked by comprehensive biosampling efforts assuring high quality and sustained availability of body liquids and tissue biopsies. We provide evidence for the feasibility of such a cohort program with deep phenotyping and high quality biosampling on parkinsonism in an environment with structural specificities and alert the international research community to our willingness to collaborate with other centers. The combination of advanced clinical phenotyping approaches including device-based assessment will create a comprehensive assessment of the disease and its variants, its interaction with comorbidities and its progression. We envision the Luxembourg Parkinson’s study as an important research platform for defining early diagnosis and progression markers that translate into stratified treatment approaches.

The gut microbiome is a key player in the immunomodulatory and protumorigenic microenvironment during colorectal cancer (CRC), as different gut-derived bacteria can induce tumour growth. However, the crosstalk between the gut microbiome and the host in relation to tumour cell metabolism remains largely unexplored. Here we show that formate, a metabolite produced by the CRC-associated bacterium Fusobacterium nucleatum, promotes CRC development. We describe molecular signatures linking CRC phenotypes with Fusobacterium abundance. Cocultures of F. nucleatum with patient-derived CRC cells display protumorigenic effects, along with a metabolic shift towards increased formate secretion and cancer glutamine metabolism. We further show that microbiome-derived formate drives CRC tumour invasion by triggering AhR signalling, while increasing cancer stemness. Finally, F. nucleatum or formate treatment in mice leads to increased tumour incidence or size, and Th17 cell expansion, which can favour proinflammatory profiles. Moving beyond observational studies, we identify formate as a gut-derived oncometabolite that is relevant for CRC progression.

IntroductionA few major clinical factors such as sex, obesity or comorbidities have already been associated with COVID-19 severity, but there is a need to identify new epidemiological, clinical, digital and biological characteristics associated with severity and perform deep phenotyping of patients according to severity. The objectives of the Predi-COVID study are (1) to identify new determinants of COVID-19 severity and (2) to conduct deep phenotyping of patients by stratifying them according to risk of complications, as well as risk factors for infection among household members of Predi-COVID participants (the Predi-COVID-H ancillary study).Methods and analysisPredi-COVID is a prospective, hybrid cohort study composed of laboratory-confirmed COVID-19 cases in Luxembourg who will be followed up remotely for 1 year to monitor their health status and symptoms. Predi-COVID-H is an ancillary cohort study on household members of index cases included in Predi-COVID to monitor symptoms and household clusters in this high-risk population. A subcohort of up to 200 Predi-COVID and 300 Predi-COVID-H participants with biological samples will be included. Severity of infection will be evaluated by occurrence and duration of hospitalisation, admission and duration of stay in intensive care units or equivalent structures, provision of and duration of supplemental oxygen and ventilation therapy, transfer to another hospital, as well as the impact of infection on daily activities following hospital discharge.Ethics and disseminationThe study has been approved by the National Research Ethics Committee of Luxembourg (study number 202003/07) in April 2020. An informed consent is signed by study participants. Scientific articles will be submitted to international peer-reviewed journals, along with press releases for lay audience for major results.Trial registration numberNCT04380987.

A daily glass of red wine associated with lifestyle changes independently improves blood lipids in patients with carotid arteriosclerosis: results from a randomized controlled trial AbstractBackground: Physical exercise and a Mediterranean diet improve serum lipid profile. The present work studied whether red wine has an effect on top of a lipid-lowering lifestyle in patients with carotid atherosclerosis.Methods: A prospective randomised unblinded trial was performed from 2009 to 2011 in 108 patients with carotid atherosclerosis, 65% of whom were already on statin therapy with a low mean LDL of 104.9 mg/dl. Half of them were advised to follow a modified Mediterranean diet and to perform moderate physical exercise during 30 min/ day (lifestyle changes) for 20 weeks. Within these two groups half of the patients were randomised either to avoid any alcohol or to drink 100 ml of red wine (women) or 200 ml of red wine (men) daily. Results: LDL was significantly lowered by 7% in the lifestyle-changes group compared to the no-lifestyle-changes group (p = 0.0296) after 20 weeks. Lifestyle changes lowered the LDL/HDL ratio after 20 weeks by 8% (p = 0.0242) and red wine independently by 13% (p = 0.0049). The effect on LDL/HDL ratio after 20 weeks was, however, more pronounced in the non-LC group. Total cholesterol (−6%; p = 0.0238) and triglycerides (−13%; p = 0.0361) were lowered significantly by lifestyle changes after 20 weeks compared to the no-lifestyle-changes group. Lipoprotein (a) was not significantly affected by any intervention. The given results are per ITT analysis. Conclusions: Lifestyle changes including a modified Mediterranean diet and physical exercise as well as a glass of red wine daily improve independently the LDL/HDL ratio in patients with carotid arteriosclerosis even though the vast majority of them was already on statin therapy. Trial registration: http://www.clinicaltrials.gov, NCT01146132