Quality of maternal and newborn care around the time of childbirth in Luxembourg during the COVID-19 pandemic: Results of the IMAgiNE EURO study.

OBJECTIVE: To investigate the quality of maternal and newborn care (QMNC) during childbirth in Luxembourg from women's perspectives. METHODS: Women giving birth in facilities in Luxembourg between March 1, 2020, and July 1, 2021, answered a validated online WHO standards-based questionnaire as part of the multicountry IMAgINE EURO study. Descriptive and multivariate quantile regression analyses were performed. RESULTS: A total of 493 women were included, representing 5.2% of women giving birth in the four maternity hospitals in Luxembourg during the study period. Most quality measures suggested high QMNC, although specific gaps were observed: 13.4% (n = 66) of women reported not being treated with dignity, 9.1% (n = 45) experienced abuse, 42.9% (n = 30) were not asked for consent prior to instrumental vaginal birth, 39.3% (n = 118) could not choose their birth position, 27% (n = 133) did not exclusively breastfeed at discharge (without significant differences over time), 20.5% (n = 101) reported an insufficient number of healthcare professionals, 20% (n = 25) did not receive information on the newborn after cesarean, and 41.2% (n = 203) reported lack of information on newborn danger signs before discharge. Multivariate analyses highlighted higher reported QMNC indexes among women born outside Luxembourg and delivering with a gynecologist, and significantly lower QMNC indexes in women with the highest education levels and those delivering in the hospital offering some private services. CONCLUSIONS: Despite maternal reports suggesting an overall high QMNC in Luxembourg, improvements are needed in specific aspects of care and communication, mostly related to maternal autonomy, respect, and support, but also number and competencies of the health workforce.

Low prevalence of relative age effects in Luxembourg's male and female youth football.

The relative age effect (RAE) is a well-established phenomenon in football. However, while the majority of previous studies focussed on established football nations, it remains unclear if the constraint of a limited population of soccer players in smaller countries associated with less strict selection procedures may reduce the risk of RAE. This study aims to investigate the RAE in Luxembourg that follows an 'open-door' selection policy in youth football due to the limited pool of players. Birthdates from all licensed and actively playing Luxembourgish youth footballers including all players of the youth national teams (396 girls and 10981 boys) competing in the season 2018/2019 were analysed and categorised into birth quarters and semesters. To further investigate a performance dependence of the RAE in amateur leagues, success was determined based on the teams' rankings at the end of the season. Differences between observed and expected birthdate distributions were calculated across all licensed players and age groups, within the national teams, and for the top- and bottom-tier football teams using chi-square statistics. While a RAE was absent across all age groups (except U7), significant RAEs with high effect sizes were observed in the top-level and national teams. These findings contrast the substantial RAE effects in large football nations and suggest that open selection systems might reflect an environmental constraint that limit the prevalence of RAE in football. Further, this study indicates that a performance dependence of the RAE is not limited to high level football but already occurs on an amateur level.

Sexual satisfaction and sexual behaviors during the COVID-19 pandemic: results from the International Sexual Health And REproductive (I-SHARE) health survey in Luxembourg.

AIM: To identify the impact of COVID-19 measures on sexual behaviors and sexual satisfaction in Luxembourg residents. METHODS: We conducted a cross-sectional online survey of adults (> 18 years of age) residing in Luxembourg, while COVID-19 restrictions were in place. The survey was available from January 15 to February 12, 2021 in four languages (French, German, English and Portuguese). Survey questions focused on masturbation, cuddling, condom use, sex frequency, sexting, cybersex, watching porn, and sexual satisfaction. RESULTS: 557 volunteers completed the survey (35.5% men, 64.3% women). Sexual satisfaction and sexual problems variables were assessed on 4-point Likert scales (0 = not at all/never to 3 = very/often). Sexual problems increased during the COVID-19 measures while sexual satisfaction decreased compared to before the introduction of COVID-19 restrictions (assessed retrospectively). Factors associated with increased odds of sexual satisfaction included having a steady relationship before COVID-19 restrictions, engaging in sexting, reporting good mental health and not altering alcohol intake. CONCLUSIONS: The context of the COVID-19 pandemic and the measures implemented in Luxembourg affected sexual behaviors and sexual satisfaction. Sexual and reproductive health care centers and health professionals in general should take these results into consideration when providing care. Recommendations on the importance of sexual health for general wellbeing and behaviors associated with sexual satisfaction should be offered and possibilities to experience sexuality while reducing contamination risks be discussed.

Associations between physical activity prior to infection and COVID-19 disease severity and symptoms: results from the prospective Predi-COVID cohort study.

OBJECTIVE: To investigate if the physical activity (PA) prior to infection is associated with the severity of the disease in patients positively tested for COVID-19, as well as with the most common symptoms. DESIGN: A cross-sectional study using baseline data from a prospective, hybrid cohort study (Predi-COVID) in Luxembourg. Data were collected from May 2020 to June 2021. SETTING: Real-life setting (at home) and hospitalised patients. PARTICIPANTS: All volunteers aged >18 years with confirmed SARS-CoV-2 infection, as determined by reverse transcription-PCR, and having completed the PA questionnaire (n=452). PRIMARY AND SECONDARY OUTCOME MEASURES: The primary outcome was disease severity (asymptomatic, mild illness and moderate illness). The secondary outcomes were self-reported symptoms. RESULTS: From the 452 patients included, 216 (48%) were female, the median (IQR) age was 42 (31-51) years, 59 (13%) were classified as asymptomatic, 287 (63%) as mild illness and 106 (24%) as moderate illness. The most prevalent symptoms were fatigue (n=294; 65%), headache (n=281; 62%) and dry cough (n=241; 53%). After adjustment, the highest PA level was associated with a lower risk of moderate illness (OR 0.37; 95% CI 0.14 to 0.98, p=0.045), fatigue (OR 0.54; 95% CI 0.30 to 0.97, p=0.040), dry cough (OR 0.55; 95% CI 0.32 to 0.96, p=0.034) and chest pain (OR 0.32; 95% CI 0.14 to 0.77, p=0.010). CONCLUSIONS: PA before COVID-19 infection was associated with a reduced risk of moderate illness severity and a reduced risk of experiencing fatigue, dry cough and chest pain, suggesting that engaging in PA may be an effective approach to minimise the severity of COVID-19. TRIAL REGISTRATION NUMBER: NCT04380987.

Risk reduction of severe outcomes in vaccinated COVID-19 cases: an analysis of surveillance data from Estonia, Ireland, Luxembourg and Slovakia, January to November 2021.

Despite high COVID-19 vaccine coverage in the EU/EEA, there are increasing reports of SARS-CoV-2 infections and hospitalisations in vaccinated individuals. Using surveillance data from Estonia, Ireland, Luxembourg and Slovakia (January-November 2021), we estimated risk reduction of severe outcomes in vaccinated cases. Increasing age remains the most important driver of severity, and vaccination significantly reduces risk in all ages for hospitalisation (adjusted relative risk (aRR): 0.32; 95% confidence interval (CI): 0.26-0.39) and death (aRR: 0.20; 95% CI: 0.13-0.29).

Estimating the impact of interventions against COVID-19: From lockdown to vaccination.

Coronavirus disease 2019 (COVID-19) is an infectious disease of humans caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). Since the first case was identified in China in December 2019 the disease has spread worldwide, leading to an ongoing pandemic. In this article, we present an agent-based model of COVID-19 in Luxembourg, and use it to estimate the impact, on cases and deaths, of interventions including testing, contact tracing, lockdown, curfew and vaccination. Our model is based on collation, with agents performing activities and moving between locations accordingly. The model is highly heterogeneous, featuring spatial clustering, over 2000 behavioural types and a 10 minute time resolution. The model is validated against COVID-19 clinical monitoring data collected in Luxembourg in 2020. Our model predicts far fewer cases and deaths than the equivalent equation-based SEIR model. In particular, with R0 = 2.45, the SEIR model infects 87% of the resident population while our agent-based model infects only around 23% of the resident population. Our simulations suggest that testing and contract tracing reduce cases substantially, but are less effective at reducing deaths. Lockdowns are very effective although costly, while the impact of an 11pm-6am curfew is relatively small. When vaccinating against a future outbreak, our results suggest that herd immunity can be achieved at relatively low coverage, with substantial levels of protection achieved with only 30% of the population fully immune. When vaccinating in the midst of an outbreak, the challenge is more difficult. In this context, we investigate the impact of vaccine efficacy, capacity, hesitancy and strategy. We conclude that, short of a permanent lockdown, vaccination is by far the most effective way to suppress and ultimately control the spread of COVID-19.

[Care pathway for Covid-19 patients in a hospital in Luxembourg]. / Parcours de soins des patients atteints de la Covid-19 dans un centre hospitalier au Luxembourg.

The current care pathway for COVID-19 patients was set up at the Centre Hospitalier de Luxembourg following the experiences of the first wave. The role of the nurse in this pathway is fundamental: she coordinates care and the multidisciplinary team as well as the families, in addition to monitoring and treating the patients. Her tool is clinical reasoning, which is the guarantee of care adapted to the needs and expectations of the patients.

Epidemiological Predictive Modeling of COVID-19 Infection: Development, Testing, and Implementation on the Population of the Benelux Union.

Since the outbreak of coronavirus disease-2019 (COVID-19), the whole world has taken interest in the mechanisms of its spread and development. Mathematical models have been valuable instruments for the study of the spread and control of infectious diseases. For that purpose, we propose a two-way approach in modeling COVID-19 spread: a susceptible, exposed, infected, recovered, deceased (SEIRD) model based on differential equations and a long short-term memory (LSTM) deep learning model. The SEIRD model is a compartmental epidemiological model with included components: susceptible, exposed, infected, recovered, deceased. In the case of the SEIRD model, official statistical data available online for countries of Belgium, Netherlands, and Luxembourg (Benelux) in the period of March 15 2020 to March 15 2021 were used. Based on them, we have calculated key parameters and forward them to the epidemiological model, which will predict the number of infected, deceased, and recovered people. Results show that the SEIRD model is able to accurately predict several peaks for all the three countries of interest, with very small root mean square error (RMSE), except for the mild cases (maximum RMSE was 240.79 ± 90.556), which can be explained by the fact that no official data were available for mild cases, but this number was derived from other statistics. On the other hand, LSTM represents a special kind of recurrent neural network structure that can comparatively learn long-term temporal dependencies. Results show that LSTM is capable of predicting several peaks based on the position of previous peaks with low values of RMSE. Higher values of RMSE are observed in the number of infected cases in Belgium (RMSE was 535.93) and Netherlands (RMSE was 434.28), and are expected because of thousands of people getting infected per day in those countries. In future studies, we will extend the models to include mobility information, variants of concern, as well as a medical intervention, etc. A prognostic model could help us predict epidemic peaks. In that way, we could react in a timely manner by introducing new or tightening existing measures before the health system is overloaded.

Modelling COVID-19 dynamics and potential for herd immunity by vaccination in Austria, Luxembourg and Sweden.

Against the COVID-19 pandemic, non-pharmaceutical interventions have been widely applied and vaccinations have taken off. The upcoming question is how the interplay between vaccinations and social measures will shape infections and hospitalizations. Hence, we extend the Susceptible-Exposed-Infectious-Removed (SEIR) model including these elements. We calibrate it to data of Luxembourg, Austria and Sweden until 15 December 2020. Sweden results having the highest fraction of undetected, Luxembourg of infected and all three being far from herd immunity in December. We quantify the level of social interaction, showing that a level around 1/3 of before the pandemic was still required in December to keep the effective reproduction number Refft below 1, for all three countries. Aiming to vaccinate the whole population within 1 year at constant rate would require on average 1,700 fully vaccinated people/day in Luxembourg, 24,000 in Austria and 28,000 in Sweden, and could lead to herd immunity only by mid summer. Herd immunity might not be reached in 2021 if too slow vaccines rollout speeds are employed. The model thus estimates which vaccination rates are too low to allow reaching herd immunity in 2021, depending on social interactions. Vaccination will considerably, but not immediately, help to curb the infection; thus limiting social interactions remains crucial for the months to come.

Perceived Ageism During the Covid-19-Crisis Is Longitudinally Related to Subjective Perceptions of Aging.

Ageism in media and society has increased sharply during the Covid-19-crisis, with expected negative consequences for the health and well-being of older adults. The current study investigates whether perceived ageism during the crisis longitudinally affects how people perceive their own aging. In June 2020, N = 611 older adults from Luxembourg [aged 60-98 years, Mage (SD) = 69.92(6.97)] participated in a survey on their perception of the crisis. In October 2020, N = 523 participated in a second measurement occasion. Participants reported on perceived ageism during the crisis in different domains, their self-perceptions of aging and subjective age. In latent longitudinal regression models, we predicted views on aging at T2 with perceived ageism at T1, while controlling for baseline views on aging and covariates. Perceived ageism at T1 increased self-perceptions of aging as social loss and yielded a trend for physical decline, while there were no effects on subjective age and self-perceptions of aging as continued growth. Views on aging are powerful predictors of well-being and health outcomes in later life. Our data suggest that being the target of ageism during the crisis negatively affects older adults' self-perceptions of aging and this impact may be felt beyond the current crisis.

COVID-19 crisis management in Luxembourg: Insights from an epidemionomic approach.

We develop an epidemionomic model that jointly analyzes the health and economic responses to the COVID-19 crisis and to the related containment and public health policy measures implemented in Luxembourg. The model has been used to produce nowcasts and forecasts at various stages of the crisis. We focus here on two key moments in time, namely the deconfinement period following the first lockdown, and the onset of the second wave. In May 2020, we predicted a high risk of a second wave that was mainly explained by the resumption of social life, low participation in large-scale testing, and reduction in teleworking practices. Simulations conducted 5 months later reveal that managing the second wave with moderately coercive measures has been epidemiologically and economically effective. Assuming a massive third (or fourth) wave will not materialize in 2021, the real GDP loss due to the second wave will be smaller than 0.4 percentage points in 2020 and 2021.

The evolution and social determinants of mental health during the first wave of the COVID-19 outbreak in Luxembourg.

Studies have been showing a negative impact of pandemic control measures on mental health. However, few studies assessed these effects longitudinally during the peak of the first wave of the COVID-19 pandemic. The goals of this study were to explore whether differential effects of COVID-19 restrictions on mental health could be observed by sex and age in a Luxembourgish nationally representative sample during the initial outbreak of COVID-19. Furthermore, we aimed to assess whether there are differences in risk and protective factors longitudinally at two assessment times. A total of 1,756 respondents aged 18 years and older (50.74% women) reported sociodemographic and socio-economic characteristics, depression, anxiety, stress, and loneliness. Women and younger respondents reported higher rates of severe depression and anxiety symptoms, suggesting higher vulnerability to the pandemic control measures. This study contributes to the investigation of mental health consequences of the pandemic and the pandemic control measures, particularly related to shifts in care task responsibilities, gender and socio-economic inequalities, as well as younger groups' uncertainty about the future.

Fourteen-day survival among older adults with severe infection with severe acute respiratory syndrome coronavirus 2 treated with corticosteroid: a cohort study.

OBJECTIVE: To assess the effectiveness of corticosteroids among older adults with coronavirus disease 2019 (COVID-19) pneumonia requiring oxygen. METHODS: We used routine care data from 36 hospitals in France and Luxembourg to assess the effectiveness of corticosteroids with at least 0.4 mg/kg/day equivalent prednisone (treatment group) versus standard of care (control group). Participants were adults aged 80 years or older with PCR-confirmed severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection or CT scan images typical of COVID-19 pneumonia, requiring oxygen ≥3 L/min, and with an inflammatory syndrome (C-reactive protein ≥40 mg/L). The primary outcome was overall survival at day 14. In our main analysis, characteristics of patients at baseline (i.e. time when patients met all inclusion criteria) were balanced by using propensity-score inverse probability of treatment weighting. RESULTS: Among the 267 patients included in the analysis, 98 were assigned to the treatment group. Their median age was 86 years (interquartile range 83-90 years) and 95% had a SARS-CoV-2 PCR-confirmed diagnosis. In total, 43/98 (43.9%) patients in the treatment group and 84/166 (50.6%) in the control group died before day 14 (weighted hazard ratio 0.67, 95% CI 0.46-0.99). The treatment and control groups did not differ significantly for the proportion of patients discharged to home/rehabilitation at day 14 (weighted relative risk 1.12, 95% CI 0.68-1.82). Twenty-two (16.7%) patients receiving corticosteroids developed adverse events, but only 11 (6.4%) from the control group. CONCLUSIONS: Corticosteroids were associated with a significant increase in the overall survival at day 14 of patients aged 80 years and older hospitalized for severe COVID-19.

Subjective Well-Being of Adolescents in Luxembourg, Germany, and Brazil During the COVID-19 Pandemic.

PURPOSE: This study explores adolescent well-being during the first wave of the COVID-19 pandemic in two high-income countries from Europe and one middle-income country from South America. The aim is to investigate the correlates of different dimensions of subjective well-being in 10- to 16-year-olds from different cultural contexts. METHODS: An online, self-report questionnaire was completed by 1,613 adolescents in Luxembourg, Germany, and Brazil between May and July 2020. The outcome variables were measures of life satisfaction and emotional well-being during the COVID-19 pandemic. The study included a range of sociodemographic, interpersonal, and intrapersonal covariates. Data were analyzed using descriptive statistics and latent variable structural equational modeling. RESULTS: A two-factor model of subjective well-being, consisting of life satisfaction and emotional well-being latent constructs, fitted well with this sample data for Luxembourg, Germany, and Brazil. Results showed that gender, socioeconomic status, intrapersonal factors, quantity and type of schoolwork, and relationships with adults were important common predictors of individual differences in subjective well-being during COVID-19. Fear of illness emerged as the strongest correlate of emotional well-being across the three countries. CONCLUSIONS: This study indicates that girls and adolescents from low-income homes may be especially vulnerable to negative secondary impacts of COVID-19 that can affect mental health. It identified several common correlates of subjective well-being in adolescents from different cultural settings, including factors that may be changeable, such as the following: the way adults listen to adolescents, schoolwork during distant learning, and fear of illness. Findings can inform the development of quality interventions for promoting the well-being of adolescents during a global pandemic.

Case series of four re-infections with a SARS-CoV-2 B.1.351 variant, Luxembourg, February 2021.

We describe four SARS-CoV-2 re-infections with a B.1.351 variant in 2021, in healthcare workers (HCWs) previously infected in 2020, before detection of this variant in Europe. Cases live in France, near the border with Luxembourg, where variants B.1.351 and B.1.1.7 circulated. All work in the same hospital unit where a cluster of COVID 19 with B1.351 variant occurred, affecting patients and HCWs. Before the cluster onset, HCWs used surgical masks, as per recommendations. After cluster onset, HCWs used FFP2 masks.

SARS-CoV-2 transmission in educational settings during an early summer epidemic wave in Luxembourg, 2020.

BACKGROUND: Following a first wave in spring and gradual easing of lockdown, Luxembourg experienced an early second epidemic wave of SARS-CoV-2 before the start of summer school holidays on 15th July. This provided the opportunity to investigate the role of school-age children and school settings for transmission. METHODS: We compared the incidence of SARS-CoV-2 in school-age children, teachers and the general working population in Luxembourg during two epidemic waves: a spring wave from March-April 2020 corresponding to general lockdown with schools being closed and May-July 2020 corresponding to schools being open. We assessed the number of secondary transmissions occurring in schools between May and July 2020 using routine contact tracing data. RESULTS: During the first wave in March-April 2020 when schools were closed, the incidence in pupils peaked at 28 per 100,000, while during the second wave in May-July 2020 when schools were open, incidence peaked 100 per 100,000. While incidence of SARS-CoV-2 was higher in adults than in children during the first spring wave, no significant difference was observed during the second wave in early summer. Between May and July 2020, we identified a total of 390 and 34 confirmed COVID-19 cases among 90,150 school-age children and 11,667 teachers, respectively. We further estimate that 179 primary cases caused 49 secondary cases in schools. While some small clusters of mainly student-to-student transmission within the same class were identified, we did not observe any large outbreaks with multiple generations of infection. CONCLUSIONS: Transmission of SARS-CoV-2 within Luxembourg schools was limited during an early summer epidemic wave in 2020. Precautionary measures including physical distancing as well as easy access to testing, systematic contact tracing appears to have been successful in mitigating transmission within educational settings.

Group testing as a strategy for COVID-19 epidemiological monitoring and community surveillance.

We propose an analysis and applications of sample pooling to the epidemiologic monitoring of COVID-19. We first introduce a model of the RT-qPCR process used to test for the presence of virus in a sample and construct a statistical model for the viral load in a typical infected individual inspired by large-scale clinical datasets. We present an application of group testing for the prevention of epidemic outbreak in closed connected communities. We then propose a method for the measure of the prevalence in a population taking into account the increased number of false negatives associated with the group testing method.

Protocol for a prospective, longitudinal cohort of people with COVID-19 and their household members to study factors associated with disease severity: the Predi-COVID study.

INTRODUCTION: A 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 ANALYSIS: Predi-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 DISSEMINATION: The 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 NUMBER: NCT04380987.

Home Treatment of Older People with Symptomatic SARS-CoV-2 Infection (COVID-19): A structured Summary of a Study Protocol for a Multi-Arm Multi-Stage (MAMS) Randomized Trial to Evaluate the Efficacy and Tolerability of Several Experimental Treatments to Reduce the Risk of Hospitalisation or Death in outpatients aged 65 years or older (COVERAGE trial).

OBJECTIVES: To assess the efficacy of several repurposed drugs to prevent hospitalisation or death in patients aged 65 or more with recent symptomatic SARS-CoV-2 infection (COVID-19) and no criteria for hospitalisation. TRIAL DESIGN: Phase III, multi-arm (5) and multi-stage (MAMS), randomized, open-label controlled superiority trial. Participants will be randomly allocated 1:1:1:1:1 to the following strategies: Arm 1: Control arm Arms 2 to 5: Experimental treatment arms Planned interim analyses will be conducted at regular intervals. Their results will be reviewed by an Independent Data and Safety Monitoring Board. Experimental arms may be terminated for futility, efficacy or toxicity before the end of the trial. New experimental arms may be added if new evidence suggests that other treatments should be tested. A feasibility and acceptability substudy as well as an immunological substudy will be conducted alongside the trial. PARTICIPANTS: Inclusion criteria are: 65-year-old or more; Positive test for SARS-CoV-2 on a nasopharyngeal swab; Symptoms onset within 3 days before diagnosis; No hospitalisation criteria; Signed informed consent; Health insurance. Exclusion criteria are: Inability to make an informed decision to participate (e.g.: dementia, guardianship); Rockwood Clinical Frailty Scale ≥7; Long QT syndrome; QTc interval > 500 ms; Heart rate <50/min; Kalaemia >5.5 mmol/L or <3.5 mmol/L; Ongoing treatment with piperaquine, halofantrine, dasatinib, nilotinib, hydroxyzine, domperidone, citalopram, escitalopram, potent inhibitors or inducers of cytochrome P450 CYP3A4 isoenzyme, repaglinide, azathioprine, 6-mercaptopurine, theophylline, pyrazinamide, warfarin; Known hypersensitivity to any of the trial drugs or to chloroquine and other 4-aminoquinolines, amodiaquine, mefloquine, glafenine, floctafenine, antrafenine, ARB; Hepatic porphyria; Liver failure (Child-Pugh stage ≥B); Stage 4 or 5 chronic kidney disease (GFR <30 mL/min/1.73 m²); Dialysis; Hypersentivity to lactose; Lactase deficiency; Abnormalities in galactose metabolism; Malabsorption syndrome; Glucose-6-phosphate dehydrogenase deficiency; Symptomatic hyperuricemia; Ileus; Colitis; Enterocolitis; Chronic hepatitis B virus disease. The trial is being conducted in France in the Bordeaux, Corse, Dijon, Nancy, Paris and Toulouse areas as well as in the Grand Duchy of Luxembourg. Participants are recruited either at home, nursing homes, general practices, primary care centres or hospital outpatient consultations. INTERVENTION AND COMPARATOR: The four experimental treatments planned in protocol version 1.2 (April 8th, 2020) are: (1) Hydroxychloroquine 200 mg, 2 tablets BID on day 0, 2 tablets QD from day 1 to 9; (2) Imatinib 400 mg, 1 tablet QD from day 0 to 9; (3) Favipiravir 200 mg, 12 tablets BID on day 0, 6 tablets BID from day 1 to 9; (4) Telmisartan 20 mg, 1 tablet QD from day 0 to 9. The comparator is a complex of vitamins and trace elements (AZINC Forme et Vitalité®), 1 capsule BID for 10 days, for which there is no reason to believe that they are active on the virus. In protocol version 1.2 (April 8th, 2020): People in the control arm will receive a combination of vitamins and trace elements; people in the experimental arms will receive hydroxychloroquine, or favipiravir, or imatinib, or telmisartan. MAIN OUTCOME: The primary outcome is the proportion of participants with an incidence of hospitalisation and/or death between inclusion and day 14 in each arm. RANDOMISATION: Participants are randomized in a 1:1:1:1:1 ratio to each arm using a web-based randomisation tool. Participants not treated with an ARB or ACEI prior to enrolment are randomized to receive the comparator or one of the four experimental drugs. Participants already treated with an ARB or ACEI are randomized to receive the comparator or one of the experimental drugs except telmisartan (i.e.: hydroxychloroquine, imatinib, or favipiravir). Randomisation is stratified on ACEI or ARBs treatment at inclusion and on the type of residence (personal home vs. nursing home). BLINDING (MASKING): This is an open-label trial. Participants, caregivers, investigators and statisticians are not blinded to group assignment. NUMBERS TO BE RANDOMISED (SAMPLE SIZE): A total of 1057 participants will be enrolled if all arms are maintained until the final analysis and no additional arm is added. Three successive futility interim analyses are planned, when the number of participants reaches 30, 60 and 102 in the control arm. Two efficacy analyses (interim n°3 and final) will be performed successively. TRIAL STATUS: This describes the Version 1.2 (April 8th, 2020) of the COVERAGE protocol that was approved by the French regulatory authority and ethics committee. The trial was opened for enrolment on April 15th, 2020 in the Nouvelle Aquitaine region (South-West France). Given the current decline of the COVID-19 pandemic in France and its unforeseeable dynamic in the coming months, new trial sites in 5 other French regions and in Luxembourg are currently being opened. A revised version of the protocol was submitted to the regulatory authority and ethics committee on June 15th, 2020. It contains the following amendments: (i) Inclusion criteria: age ≥65 replaced by age ≥60; time since first symptoms <3 days replaced by time since first symptoms <5 days; (ii) Withdrawal of the hydroxychloroquine arm (due to external data); (iii) increase in the number of trial sites. TRIAL REGISTRATION: The trial was registered on Clinical Trials.gov on April 22nd, 2020 (Identifier: NCT04356495): and on EudraCT on April 10th, 2020 (Identifier: 2020-001435-27). FULL PROTOCOL: The full protocol is attached as an additional file, accessible from the Trials website (Additional file 1). In the interest of expediting dissemination of this material, the familiar formatting has been eliminated; this Letter serves as a summary of the key elements of the full protocol. The study protocol has been reported in accordance with the Standard Protocol Items: Recommendations for Clinical Interventional Trials (SPIRIT) guidelines (Additional file 2).

Evolving social contact patterns during the COVID-19 crisis in Luxembourg.

We conducted an internet survey using Survey Monkey over six weeks to evaluate the impact of the government interventions on social contact patterns in Luxembourg. Participants were recruited via the science.lu website on March 25, April 2, April 16, May 1 during lockdown, and June 12 and June 25 after the lockdown to provide an estimate of their number of contacts within the previous 24 hours. During the lockdown, a total of 5,644 survey participants with a mean age of 44.2 years reported 18,118 contacts (mean = 3.2, IQR 1-4). The average number of contacts per day increased by 24% from 2.9 to 3.6 over the lockdown period. The average number of contacts decreased with age: 4.2 (IQR 2-5) for participants below 25 years and 1.7 (IQR 1-2) for participants above 64 years. Residents of Portuguese nationality reported a higher number of contacts (mean = 4.3, IQR 2-5) than Luxembourgish (mean = 3.5, IQR 2-4) or other foreign residents, respectively. After lockdown, 1,119 participants reported 7,974 contacts with 7.1 (IQR 3-9) contacts per day on average, of which 61.7% (4,917/7,974) occurred without a facemask (mean = 4.9, IQR 2-6). While the number of social contacts was substantially lower during the lockdown by more than 80% compared to the pre-pandemic period, we observed a more recent 121% increase during the post lockdown period showing an increased potential for COVID-19 spread. Monitoring social contacts is an important indicator to estimate the possible impact of government interventions on social contacts and the COVID-19 spread in the coming months.