High vaccine effectiveness against severe COVID-19 outcomes and population preventable fraction during the Omicron era in Luxembourg: A nationwide retrospective risk factor analysis.

BACKGROUND: Luxembourg experienced major consecutive SARS-CoV-2 infection waves due to Omicron variants during 2022 while having achieved a high vaccination coverage in 2021. We investigated the risk factors associated to severe outcomes (i.e., hospitalisation, deaths) and estimated vaccine effectiveness (VE) as well as the role of immunity conferred by prior infections against severe outcomes in adults. METHODS: We linked reported SARS-CoV-2 cases among residents aged ≥ 20 years with vaccination data and SARS-CoV-2 related hospitalisations and deaths. Cases were followed-up until day 14 for COVID-19 related hospital admission and up to day 28 for mortality after a positive test. We analysed the association between the vaccination status and severe forms using proportional Cox regression, adjusting for previous infection, age, sex and nursing homes residency. VE was measured as 1-adjusted hazard ratio of vaccinated vs unvaccinated individuals. The population preventable fraction was computed using the adjusted hazard ratio and the proportion of cases within the vaccination category. RESULTS: Between December 2021, and March 2023, we recorded 187143 SARS-CoV-2 cases, 1728 (0.93%) hospitalizations and 611 (0.33%) deaths. The risk of severe outcomes increased with age, was higher among men and nursing home residents. Compared to unvaccinated adults, VE against hospitalization was 38.8% (95%CI: 28.1%-47.8%) for a complete primary cycle of vaccination, 62.1% (95%CI: 57.0%-66.7%) for one booster, and 71.6% (95%CI: 66.7%-76.2%) for two booster doses. VE against death was respectively 49.5% (95%CI: 30.8%-63.3%), 69.0% (95%CI: 61.2%-75.3%) and 76.2% (95%CI: 68.4%-82.2%). Previous infection was not associated with lower risk of hospitalisation or mortality. The vaccination lowered mortality by 55.8 % (95%CI: 46.3%-62.8%) and reduced hospital admissions by 49.1% (95%CI: 43.4%-54.4%). CONCLUSIONS: Complete vaccination and booster but not previous infection were protective against hospitalization and death. The vaccination program in Luxembourg led to substantial reductions in SARS-CoV-2-related mortality and hospitalizations at the population level.

Impact of nirsevimab prophylaxis on paediatric respiratory syncytial virus (RSV)-related hospitalisations during the initial 2023/24 season in Luxembourg.

After Luxembourg introduced nirsevimab immunisation against respiratory syncytial virus (RSV), estimated neonatal coverage was 84% (1,277 doses/1,524 births) in 2023. That year, paediatric RSV-related hospitalisations, especially concerning infants < 6 months old (n = 72) seemed to decrease compared to the same period in 2022 (n = 232). In 2023, hospitalised children's mean age increased (14.4 months vs 7.8 months in 2022; p < 0.001) and hospital-stay length decreased (3.2 days vs 5.1 days; p < 0.001). In infants < 6 months old, intensive-care unit admissions appeared to drop (n = 28 vs 9). This suggests that nirsevimab prophylaxis reduced severe RSV infections, particularly in infants < 6 months old, thereby alleviating healthcare strain.

A standardised protocol for relative SARS-CoV-2 variant severity assessment, applied to Omicron BA.1 and Delta in six European countries, October 2021 to February 2022.

Several SARS-CoV-2 variants that evolved during the COVID-19 pandemic have appeared to differ in severity, based on analyses of single-country datasets. With decreased testing and sequencing, international collaborative studies will become increasingly important for timely assessment of the severity of new variants. Therefore, a joint WHO Regional Office for Europe and ECDC working group was formed to produce and pilot a standardised study protocol to estimate relative case-severity of SARS-CoV-2 variants during periods when two variants were co-circulating. The study protocol and its associated statistical analysis code was applied by investigators in Denmark, England, Luxembourg, Norway, Portugal and Scotland to assess the severity of cases with the Omicron BA.1 virus variant relative to Delta. After pooling estimates using meta-analysis methods (random effects estimates), the risk of hospital admission (adjusted hazard ratio (aHR) = 0.41; 95% confidence interval (CI): 0.31-0.54), admission to intensive care unit (aHR = 0.12; 95% CI: 0.05-0.27) and death (aHR = 0.31; 95% CI: 0.28-0.35) was lower for Omicron BA.1 compared with Delta cases. The aHRs varied by age group and vaccination status. In conclusion, this study demonstrates the feasibility of conducting variant severity analyses in a multinational collaborative framework and adds evidence for the reduced severity of the Omicron BA.1 variant.

A Molecular and Epidemiological Investigation of a Large SARS-CoV-2 Outbreak in a Long-Term Care Facility in Luxembourg, 2021.

In spring 2021, a long-term care facility (LTCF) of 154 residents in Luxembourg experienced a large severe, acute respiratory-syndrome coronavirus 2 (SARS-CoV-2) outbreak a few days after a vaccination campaign. We conducted an outbreak investigation and a serosurvey two months after the outbreak, compared attack rates (AR) among residents and staff, and calculated hospitalization and case-fatality rates (CFR). Whole genome sequencing (WGS) was performed to detect variants in available samples and results were compared to genomes published on GISAID. Eighty-four (55%) residents and forty-five (26%) staff members tested positive for SARS-CoV-2; eighteen (21%) residents and one (2.2%) staff member were hospitalized, and twenty-three (CFR: 27%) residents died. Twenty-seven (21% of cases) experienced a reinfection. Sequencing identified seventy-seven cases (97% of sequenced cases) with B.1.1.420 and two cases among staff with B.1.351. The outbreak strain B.1.1.420 formed a separate cluster from cases from other European countries. Convalescent and vaccinated residents had higher anti-SARS-CoV-2 IgG antibody concentrations than vaccinated residents without infection (98% vs. 52%, respectively, with >120 RU/mL, p < 0.001). We documented an extensive outbreak of SARS-CoV-2 in an LTCF due to the presence of a specific variant leading to high CFR. Infection in vaccinated residents increased antibody responses. A single vaccine dose was insufficient to mitigate the outbreak.

Challenges and benefits of integrating diverse sampling strategies in the observation of cardiovascular risk factors (ORISCAV-LUX 2) study.

BACKGROUND: It is challenging to manage data collection as planned and creation of opportunities to adapt during the course of enrolment may be needed. This paper aims to summarize the different sampling strategies adopted in the second wave of Observation of Cardiovascular Risk Factors (ORISCAV-LUX, 2016-17), with a focus on population coverage and sample representativeness. METHODS: Data from the first nationwide cross-sectional, population-based ORISCAV-LUX survey, 2007-08 and from the newly complementary sample recruited via different pathways, nine years later were analysed. First, we compare the socio-demographic characteristics and health profiles between baseline participants and non-participants to the second wave. Then, we describe the distribution of subjects across different strategy-specific samples and performed a comparison of the overall ORISCAV-LUX2 sample to the national population according to stratification criteria. RESULTS: For the baseline sample (1209 subjects), the participants (660) were younger than the non-participants (549), with a significant difference in average ages (44 vs 45.8 years; P = 0.019). There was a significant difference in terms of education level (P < 0.0001), 218 (33%) participants having university qualification vs. 95 (18%) non-participants. The participants seemed having better health perception (p < 0.0001); 455 (70.3%) self-reported good or very good health perception compared to 312 (58.2%) non-participants. The prevalence of obesity (P < 0.0001), hypertension (P < 0.0001), diabetes (P = 0.007), and mean values of related biomarkers were significantly higher among the non-participants. The overall sample (1558 participants) was mainly composed of randomly selected subjects, including 660 from the baseline sample and 455 from other health examination survey sample and 269 from civil registry sample (constituting in total 88.8%), against only 174 volunteers (11.2%), with significantly different characteristics and health status. The ORISCAV-LUX2 sample was representative of national population for geographical district, but not for sex and age; the younger (25-34 years) and older (65-79 years) being underrepresented, whereas middle-aged adults being over-represented, with significant sex-specific difference (p < 0.0001). CONCLUSION: This study represents a careful first-stage analysis of the ORISCAV-LUX2 sample, based on available information on participants and non-participants. The ORISCAV-LUX datasets represents a relevant tool for epidemiological research and a basis for health monitoring and evidence-based prevention of cardiometabolic risk in Luxembourg.

"To survey or to register" is that the question for estimating population incidence of injuries?

BACKGROUND: Measuring the true incidence of injury or medically attended injury is challenging. Population surveys, despite problems with recall and selection bias, remain the only source of information for injury incidence calculation in many countries. Emergency department (ED) registry based data provide an alternative source.The aim of this study is to compare the yearly incidence of hospital treated Home and Leisure Injuries (HLI), and Road Traffic Injuries (RTI) estimated by survey-based and register-based methods and combine information from both sources in to a comprehensive injury burden pyramide. METHODS: Data from Luxemburg's European Health Examination Survey (EHES-LUX), European Health Interview Survey (EHIS) and ED surveillance system Injury Data Base (IDB) collected in 2013, were used. EHES-LUX data on 1529 residents 25-64 years old, were collected between February 2013-January 2015. EHIS data on 4004 other residents aged 15+ years old, were collected between February and December 2014. Participants reported last year's injuries at home, leisure and traffic and treatment received. Two-sided exact binomial tests were used to compare incidences from registry with the incidences of each survey by age group and prevention domain. Data from surveys and register were combined to build an RTI and HLI burden pyramide for the 25-64 years old. This project was part of the European Union project BRIDGE-Health (BRidging Information and Data Generation for Evidence-based Health Policy and Research). RESULTS: Among 25-64 years old the incidence of hospital treated injuries per thousand population was 60.1 (95% CI: 59.2-60.9) according to IDB, 62.1 (95% CI: 50.6-75.4) according to EHES-LUX and 53.2 (95% CI: 45.0-62.4) according to EHIS. The incidence of hospital admissions was 3.7 (95% CI: 3.5-4.0) per thousand population from IDB-Luxembourg, 12.4 (95% CI: 7.5-19.3) from EHES-LUX and 18.0 (95% CI: 13.3-23.8) from EHIS. For 15+ years-old incidence of hospital treated HLI was 62.8 (95% CI: 62.1-63.5) per thousand population according to IDB whereas the corresponding EHIS estimate was lower at 46.9 (95% CI: 40.4-54.0). About half of HLI and RTI of the 25-64 years old were treated in hospital. CONCLUSION: The overall incidence estimate of hospital treated injuries from both methods does not differ for the 25-64 years old. Surveys overestimate the number of hospital admissions, probably due to memory bias. For people aged 15+ years, the survey estimate is lower than the register estimate for hospital treated HLI injuries, probably due to selection and recall biases. ED based registry data is to be preferred as single source for estimating the incidence of hospital treated injuries in all age groups.

Isolated limb perfusion: distinct tourniquet and tumor necrosis factor effects on the early hemodynamic response.

HYPOTHESIS: Recent evidence indicates that tumor response rates after isolated limb perfusion (ILP) are improved when tumor necrosis factor (TNF) is added to the locoregional perfusion of high doses of chemotherapy. Other factors, related to the patient or the ILP procedure, may interfere with the specific role of TNF in the early hemodynamic response after ILP with TNF and high-dose chemotherapy. DESIGN: Case-control study. SETTING: Tertiary care university hospital. PATIENTS: Thirty-eight patients with a locoregionally advanced tumor of a limb treated by ILP with TNF and high-dose chemotherapy (TNF group) were compared with 31 similar patients treated by ILP with high-dose chemotherapy alone (non-TNF group). INTERVENTIONS: Swan-Ganz catheter hemodynamic recordings, patients' treatment data collection, and TNF and interleukin 6 plasma level measurements at regular intervals during the first 36 hours following ILP. MAIN OUTCOME MEASURES: Hemodynamic profile and total fluid and catecholamine administration. RESULTS: In the TNF group, significant changes were observed (P<.006): the mean arterial pressure and the systemic vascular resistance index decreased, and the temperature, heart rate, and cardiac index increased. These hemodynamic alterations started when the ILP tourniquet was released (ie, when or shortly after the systemic TNF levels were the highest). The minimal mean arterial pressure, the minimal systemic vascular resistance index, the maximal cardiac index, the intensive care unit stay, and the interleukin 6 maximal systemic levels were significantly (P<.001 for all) correlated to the log(10) of the systemic TNF level. In the non-TNF group, only a brief decrease in the blood pressure following tourniquet release and an increase in the temperature and in the heart rate were statistically significant (P<.006). Despite significantly more fluid and catecholamine administration in the TNF group, the mean arterial pressure and the systemic vascular resistance index were significantly (P<.001) lower than in the non-TNF group. CONCLUSIONS: Release of the tourniquet induces a blood pressure decrease that lasts less than 1 hour in the absence of TNF and that is distinct from the septic shock-like hemodynamic profile following TNF administration. The systemic TNF levels are correlated to this hemodynamic response, which can be observed even at low TNF levels.