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Covid-19 taskforce

Predi-COVID preliminary results

The Luxembourgish cohort study shows encouraging participation rates and sees its protocol published in international peer-reviewed journal
The Predi-COVID nurse team.

Launched under the aegis of the Research Luxembourg COVID-19 Task Force on April 24th, “Predi-COVID” is a cohort study promoted by the Luxembourg Institute of Health that aims to identify the key risk factors and biomarkers associated with COVID-19 severity and comprehend the long-term health consequences of the disease. Predi-COVID will contribute to a better understanding of the heterogeneity observed in disease severity and prognosis, ultimately enabling the accurate evaluation of patients infected with SARS-CoV-2 and more personalised care recommendations. The protocol of the study was published on November 24th in the ‘British Medical Journal Open’, reinforcing the international visibility and success of this highly collaborative “Made in Luxembourg” project. 

The study goals

Predi-COVID was launched with the goal of defining which patient profiles can be associated with a more severe prognosis. The study aims to identify the clinical, epidemiological and socio-demographic characteristics, as well as specific biomarkers from both the SARS CoV-2 virus and the patient, which can help predict the way the disease will evolve in a given individual, according notably to his immune profile.

Predi-COVID and Predi-COVID-H: patient recruitment and operational aspects

The research team has been establishing a cohort of people over the age of 18 positive for SARS CoV-2. All newly diagnosed individuals in Luxembourg can participate in Predi-COVID, upon agreeing to share their data for research purposes. In parallel to Predi-COVID, the ancillary study “Predi-COVID-H” was launched to include household members of COVID-19 positive participants to study the transmission of the virus in this high-risk population. The recruitment and data/sample collection phase started on May 5th and was initially planned to last until December 2020, although an extension period until late June 2021 is being requested.

The health evolution and symptoms of the enrolled patients are followed daily through different remote digital tools, depending on whether patients are at home or at the hospital, for 14 days from the time of confirmation of diagnosis. Short additional evaluations are also performed monthly for up to 12 months, to assess potential long-term consequences of COVID-19. Innovative digital data, specifically voice recordings, is also collected as part of the study. More detailed clinical and digital data and associated biological samples is gathered from a subset of at least 200 volunteers from the Predi-COVID cohort and from 100 Predi-COVID-H participants, in order to better characterise symptoms and clearly define the different outcomes. Upon inclusion in the study and after three weeks, several biological samples — including blood, nasal and oral swabs, saliva and stool — are collected from participants to identify human and viral predictive markers.

Preliminary results: participant recruitment, data collection, symptoms and vocal biomarkers 

Since May 5th – the date of enrolment of the first participant – and as of November 10th, 1406 and 67 eligible subjects have been contacted by phone for inclusion in Predi-COVID and in Predi-COVID-H, respectively, 556 of which agreed to be included in the former and 48 in the latter. On average, participants are 39 years old.  In terms of biological samples, the team has been establishing a unique biobank to study COVID-19, already boasting 627 specimens collected during the baseline and follow-up visits. This collection includes blood, sputum, swabs, stool and hair samples.

The preliminary findings also indicate that the majority of the enrolled population experienced few or mild symptoms. The most prevalent symptoms at admission included fever (26.2% of participants), cough (23.3%), runny nose (12.2%) and sore throat (10.8%), while the most common comorbidities and risk factors include smoking (18.1% of participants), asthma (5.4%), diabetes (4.7%), chronic heart disease (3.6%) and obesity (3.3%).

Furthermore, a total of 3,290 voice recordings has been made available by 245 participants using the CoLive LIH smartphone app, with multiple recordings per person to allow the study of the evolution of voice characteristics over time. These will enable the identification of “vocal biomarkers” of frequently observed symptoms in COVID-19 patients, such as respiratory syndromes, fatigue, anxiety or negative emotions related to COVID-19, which could subsequently be used for the easy remote monitoring of patients at home.

We are delighted with the results obtained thus far. The greater the number of participants the more accurate the final results. Besides, we are now collaborating with the Centre Hospitalier de Luxembourg to envisage the inclusion of up to 100 COVID-19 positive children in Predi-COVID and up to 30 children from affected households in Predi-COVID-H”, states Prof Markus Ollert, Director of the LIH Department of Infection and Immunity and co-Principal Investigator of Predi-COVID.

We are very grateful to the Health Inspection Department of the Ministry of Health for the unwavering support and excellent collaboration throughout, which are key to the success of the study. The protocol has recently been published in a renowned international journal and will serve as the core publication to cite for all future work based on Predi-COVID data. So far, nine ancillary projects funded by the Luxembourg National Research Fund or by the European Commission’s Horizon 2020 programme are already using Predi-COVID data”, concludes Dr Guy Fagherazzi of the LIH Department of Population Health, co-Principal Investigator of Predi-COVID and first author of the publication.   

The full study protocol was published in the ‘British Medical Journal Open’ on November 24th. It is accessible here

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Covid-19 taskforce

Large-scale testing operations: Conclusion of phase 1 and launch of phase 2

Ministry of Health to lead the second phase as of mid-September.
On Monday, September 14th, the Minister of Higher Education and Research, Claude Meisch, the Minister of Health, Paulette Lenert, and the Research Luxembourg (RL) COVID-19 Task Force held a press conference in Dudelange to officially conclude the first phase of the large-scale testing, led by the Luxembourg Institute of Health together with the Research Luxembourg community. The operations of the second phase have been handed over to the Health Directorate of the Ministry of Health and will start mid-September.

As part of the exit strategy, Luxembourg has implemented an extensive and unique nation-wide testing campaign, inviting its residents and cross-border workers to voluntarily get tested for COVID19. The aim of this large-scale testing (LST) initiative was to limit the spread of the novel SARS-CoV-2 virus by identifying positive cases early, including among asymptomatic persons, thereby breaking infection chains. At the same time, LST aims to contribute to the close monitoring of the spread of the virus among our population.

The first phase of the LST, coordinated by the Luxembourg Institute of Health (LIH), ran from 27 May until 27 July and relied on 16 ‘drive-through’ and 1 ‘walk-through’ test stations, with a maximum theoretical capacity of 20,000 tests per day. The population was divided into three main categories. The first category was composed of people exposed to a high infectious risk by their professional activity (such as healthcare professionals) whereas the second category consisted of those having resumed their professional activity or about to get back to work. The third category encompassed representative samples of the general population. The recurring testing of the contingents and the rigorous contact tracing not only aims at avoiding new infection chains but also at providing decision makers with evidence-based data.

An extension period prior to the beginning of Phase II was set up during the summer period until 15 September with the aim of monitoring the evolution of the epidemic also during the summer months with a particular accent on people coming back from holidays, those professions specifically linked to the holiday period (Horesca, seasonal workers) and the school start.

In total, 1,520,445 invitations to LST were sent, and 560,082 tests were conducted covering 307,751 Luxembourg residents, reflecting an overall participation rate of almost 50 % of the resident population.

The second phase of the LST will be coordinated by the Health Directorate of the Ministry of Health and is set to run between 16 September 2020 and March 2021, with a capacity of 53,000 tests per week. Building on the experience gained during the first phase, which showed a relatively low prevalence rate, the second phase of the strategy will narrow the focus of the tests and target specifically the population most exposed to the virus, while at the same time allowing for capacities to be adjusted in a timely manner to the evolution of the situation and over a longer period of time than the first phase. This nuanced approach will foster a more precise meshing of the population and a more efficient reactiveness. More detailed information as to this new phase of the LST will be provided by Health Minister Paulette Lenert during a press conference on 24 September.

The handover press conference, which took place at the premises of the Integrated Biobank of Luxembourg (IBBL) in Dudelange in the presence of the Minister of Higher Education and Research, Claude Meisch and the Minister of Health Paulette Lenert, brought together all relevant stakeholders including the CEOs of Research Luxembourg-member institutions, the spokespersons of the RL Task Force, members of the LST scientific advisory board and representatives of Laboratoires Réunis.

As the work of Research Luxembourg on the large-scale testing campaign draws to a close, we would like to sincerely thank all the partners who contributed to the success of this extraordinary effort, particularly Laboratoires Réunis and the staff of Research Luxembourg member institutes

Prof Ulf Nehrbass, CEO of LIH and spokesman of the RL COVID-19 Task Force.

This unparalleled initiative has been widely recognised at the international level, further strengthening the country’s reputation as a leader in public health and biomedical research

Prof Paul Wilmes from the University of Luxembourg’s Luxembourg Centre of Systems Biomedicine (LCSB), deputy spokesman of the Task Force.

The strength of our response to the pandemic lies in the tight connection between public health initiatives such as the large-scale testing and the outstanding research efforts of Luxembourg’s research institutions. This synergy plays a fundamental role in providing tangible solutions to societal issues

Claude Meisch, Minister for Higher Education and Research.

The large scale testing project has confirmed the high level of resilience, adaptability and reactiveness of our country as we face an unprecedented crisis of international dimension. It will reinforce our preparedness all along the evolution of the epidemic. The second phase will consolidate our position as a leader in large-scale testing and will be part of the government’s efforts to fight the virus, ideally until the crisis ends, while allowing for a particular attention to be put on specific target groups

Paulette Lenert, Minister of Health.

Communicated by the Ministry of Higher Education and Research, the Ministry of Health and the Luxembourg Institute of Health. Originally published on lih.lu

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Covid-19 taskforce

Use of new FFP2 masks – ensuring safety & security in large scale testing stations

In the testing stations, the safety and security of the staff collecting samples has been and is being ensured by redundant protection measures with masks and face shields. These measures are strictly respected at all times.  The compliance of these measures and quality of the material being used in that framework is being closely monitored by Laboratoire Réunis, along with their sub-contracters for the large scale testing.

The masks used on the stations were CE labeled, certified by two testing laboratories and all certificates stating compliance with security & safety requirements had been provided.  However, lab reports recently suggested that the tests of some CE masks, including the masks being used at the stations, were not accurate. 

In light of this information, additional tests have been commissioned in an independent Belgian laboratory.  The results of the test received on 3 July 2020 state that the filtration rate of the tested masks is 93.39 %, as compared to  94% required for FFP2 masks. This means there is a differential of 0,61%.

As a consequence and as a precautionary measure, all masks of this model currently being in circulation are being collected, and will no longer be used by the staff as of this afternoon, 3 July 2020 at 4:00 p.m.  Instead, employees will be given certified 3M FFP2 masks used in the national hospitals.
Regular testing of the staff members working in the stations is also part of the standard security protocol. 

Safety and security are a priority for all partners involved in the large scale testing and all measures will be taken to ensure the highest standards are being maintained.

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Efficient security concept

All Large Scale Testing (LST) related employees are tested at two-week intervals to ensure maximum safety. As with all working groups, there is a possibility that asymptomatic positives may carry the virus and could be potentially contagious. Some days ago, one laboratory employee was thus actually identified positively. This person was asymptomatic with a low viral load and was immediately sent to quarantine. As the person did not work at the actual test stations but was treating the samples in the laboratory, he was at no point in contact with participants of the Large Scale Testing. A subsequent contact tracing process identified two other infected laboratory employees, also asymptomatic with very low virus titers. The head of the Inspection Sanitaire was immediately informed, and the follow-up was carried out according to the guidelines of the Inspection Sanitaire. 

As the three staff members were at no point in contact with participants of the Large Scale Testing it can be excluded that persons invited to the test were infected by one of these employees. Nevertheless, this case highlights once more the importance of systematic testing even if there are no symptoms apparent at all.

The security measures at the test stations are very high. Employees are equipped with masks, gloves, face shields, special overalls and disinfectants. Persons in the laboratories are also equipped with masks, gloves and laboratory coats (and face shields if necessary). In addition, like all workers who are exposed to a high number of contacts every day (healthcare, hairdressers, etc.), they are tested for the novel coronavirus every two weeks.

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CON-VINCE Study – Behind the scenes (PART I)

CON-VINCE as a role model for translational research collaboration in Luxembourg (PART I)
IBBL a as key integrator

On 8th April, the CON-VINCE study was officially launched, with the aim to assess the spread dynamics of the COVID-19 disease among the Luxembourgish population.

Only 2 days later, all necessary material for starting up was already available (many thanks to LIH Buildings & Equipments team), coordination between the numerous partners around a single workflow was optimal, and all security conditions (many thanks to LIH Compliance Office team) were met to start the study. A real feat!

Within just 10 days, 1862 people were recruited, biosampled and tested!

Throwback to a logistical, technical and human challenge, which was met thanks to the incredible collaboration of all the IBBL, LIH, LCSB, CHL staff and partner laboratories from BioNext, Ketterthill and Laboratoires Réunis.


(from left to right) Top Pic: Claire, Ana Lopes, Laura George, Margaux Henry, Maeva Munsch, Florian Simon, bottom left: Maeva M. Manuel C. François Massart (LCSB), Olivia Domingues, bottom right: Florian Simon, Charlene Verschueren, Ana Lopes, Margaux Schmitt, Bruno Santos 

Such an ant work was carried out by the IBBL Biorepository team and various volunteers. IBBL acted as a leader in the biosampling task force together with other stakeholders. Recruitment, as well as the coordination of collection partners, was a key point.

A huge thanks to IBBL Biorepository and Biorefinery teams who gave their all without counting the hours, so that everything could work smoothly!

As a result, in only 10 days, 3,370 kits for the collection of blood and pharyngeal samples and 1,650 kits for the collection of stool samples were distributed to the country’s partner laboratories at an unprecedented cadence.

Top left Pic: Maeva Munsch, Florian Simon, Top right: Simon bottom left: Laure Pauly, Valérie Schröder, bottom right: Katy Beaumont, Maeva M. et Florian S.

Blood and naso-pharyngeal samples from study participants collected at the 3 partner laboratories  (Ketterthill, BioneXt and Laboratoires Réunis) and including home visits, were and transported (twice a day, sometimes more) to IBBL Biorepository by Biologistics (important role in the quick start of this study).

They were then dispatched as follows:

  • naso-pharyngeal swabs to the LNS for SARS-CoV2 virus detection by amplifying ribonucleic acid (RNA) before returning to IBBL to be stored
  • blood samples to Biorefinery team for “processing”
  • transfer of forms for data encoding (cf step 5 photo bottom left)
Top left: Olivia Domingues., Mareike Neumann, Monica Marchese, Top right: Camille Bellora, Kate Sokolowska bottom left: Olivia Domingues, Charlene Verschueren, Achilleas Pexeras, Margaux Schmitt, Lucie Remark, Francois Massart bottom right Borja GOMEZ RAMOS, Olivia Domingues ,Margaux Schmitt

The “Processing” (manual and automated) consists in preparing different biological fractions for storage (serum or plasma for example). Training in the management of serum and plasma, naso-pharyngeal swabs, extracted RNA and stool aliquoting was necessary for volunteers and was organized in record time. The treated samples could then be redistributed to the LNS and LIH for analysis.

Daily processing of samples from 39 to 349 patients per day which, at the end of the first wave, allowed the storage of more than 37,000 aliquots, a large part of which was already used for research purposes within CON-VINCE and beyond.

Top left: Linda Hansen; bottom left pic: Maxime Hansen, Laure Pauly, Valerie Schröder; right: Femke Wauters. All from the Parkinson Research Clinic of NCER-PD.

A proper data collection was key to carry out this study.

Proper data encoding of the paper forms received with the samples was key to carry out this study and was done by our clinical team partners at CHL and UL. To link the participants to their samples through the paper forms and their questionnaire answers, the data team of the LCSB Computing Platform worked day and night from the beginning of the study to set up the complex and secure data infrastructure. This allows the information to be properly stored and synchronized, and updated daily with the results of the tests for the virus.

All those activities are still ongoing with the same team spirit! Thumbs up to all teams working on this great project!

“This unprecedented study, due to its complexity and urgency, was like the outline of a music score, which each one of us fed with his musical orientations. Conductors agreed, musicians practiced, others discovered their instruments, adapted, trained and above all helped each other, all in record time. The ultimate goal is to play this collaborative score in unison. Objective achieved: The melody is there! “

Katy Beaumont, Head of BioRepository at IBBL and COVID Fighter.
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The experts behind Luxembourg’s Covid-19 fight: Interview with Prof Rejko Krüger

Prof Rejko Krüger (RK) is the Director of Transversal Translational Medicine (TTM) at LIH. As a medical doctor and researcher, he is an internationally recognised “clinician scientist”, expert in both the clinical and research sides of neurodegenerative diseases, as well as in the development of translational cohort studies. In the context of the COVID-19 pandemic, Prof Krüger and his team are currently involved in the coordination of the CON-VINCE study. In this short interview, he explains his expertise and participation in ongoing COVID-19 projects.
Prof Krüger, could you tell us more about your background and expertise?

RK: I am both a neurologist, specialised in movement disorders and neurodegeneration, and a neuroscientist. As such, I play a dual role in the healthcare and biomedical research sectors. Indeed, on the one hand, I exert my medical profession at the Neurology Department of the Centre Hospitalier de Luxembourg (CHL), where I carry out patient consultations. On the other, I am involved in fundamental and clinical research across the key research institutes in Luxembourg. Indeed, I hold concomitant positions at the University of Luxembourg as Professor of Neuroscience, I supervise a clinical and experimental research group on Parkinson’s disease at the Luxembourg Centre for Biomedicine Systems (LCSB) at the University of Luxembourg and, as of June 2019, I joined LIH as Director of the newly created Transversal Translational Medicine (TTM). Through these positions, my priority is to create a ‘bridge’ between fundamental and clinical research, bringing together all the stakeholders involved in healthcare provision to achieve what is known as integrated care, that is a patient-centric approach based on the concerted functioning of all concerned parties at the funding, administrative, organisational, service delivery and clinical levels.

Odoo CMS - a big picture
Prof Rejko Krüger
How is your expertise relevant in the current COVID-19 context?

RK: As the coordinator of the National Centre of Excellence in Research on Parkinson’s disease (NCER-PD) — Luxembourg’s flagship translational programme on neurodegeneration — and Director of TTM, I have acquired a strong expertise in the conception and implementation of translational cohort studies. Specifically, my team and I are working towards the translation of the “template” developed for neurodegenerative disorders under NCER-PD to other disease areas, such as cancer and immunity. This experience has proved to be crucial in the current COVID-19 situation. Indeed, in the context of the ongoing CON-VINCE study, we were able to establish a cohort of over 1,800 individuals representative of the Luxembourg population in just three weeks. As a reference, it took four years to recruit the 1,600 volunteers for NCER-PD – of course with a different design always adapted to the specific conditions. My extensive network and deep knowledge of the Luxembourg biomedical ecosystem and its players have also proved to be essential in this respect.

What is your specific role in the ongoing COVID-19 initiatives of the Research Luxembourg taskforce?

RK: I am currently active on many fronts in the fight against COVID-19. My main role is to coordinate the CON-VINCE study, which aims to identify asymptomatic individuals to assess the spread of the disease in Luxembourg. The main challenge we encountered was to decide on the approach to be adopted to set up and recruit a cohort of people representative of the Luxembourg population in such a short timeframe. We therefore decided to collaborate with the market research company TNS-ILRES since they already had a representative cohort ready. This helped us speed up the process and get the study up and running very quickly. In addition, I am also involved across many of the other work packages of the Research Luxembourg taskforce, since these initiatives are all interconnected with each other. For instance, I am contributing to the Predi-COVID study by referring participants from the CON-VINCE cohort who have tested positive for the SARS CoV-2 virus and have COVID-19 symptoms to the team in charge of Predi-COVID, in order to help them build up the cohort of COVID-positive patients. Similarly, I am collaborating on the work package on the implementation of eHealth solutions for hospitalised and ambulatory patients, since CON-VINCE will rely on the development and use of an application to monitor participants and collect their data. Finally, we are also collaborating with the work package aiming to increase Luxembourg’s diagnostic capacity and large-scale testing.

Could you tell us more about your internal and external collaborators and their roles?

RK: The complexity of these projects requires a particularly strong teamwork and collaboration with numerous partners, both internal and external. Indeed, each task is marked by the close interaction between colleagues within and outside LIH. For instance, the sample collection and logistics aspect of the CON-VINCE study relied heavily on the joint work of various partner laboratories in Luxembourg, namely Ketterthill, Laboratoires Réunis and BioneXt Lab, and the Integrated Biobank of Luxembourg (IBBL). The laboratories are in charge of sample collection from participants, while IBBL plays the crucial role of preparing the collection kits, carrying out quality control tests on the samples and overseeing the overall logistics. Moreover, the commitment of many volunteers and staff members from LIH, as well as from the University of Luxembourg, the Luxembourg Centre of Systems Biomedicine (LCSB), the Laboratoire National de Santé (LNS) and CHL, is essential in enabling the smooth running of the project. The NCER-PD and Parkinson Clinic teams were also mobilised to contribute to the study. I would also like to specifically mention the remarkable work of the CON-VINCE project management team, including Clarissa Gomes, who manages both NCER-PD and CON-VINCE, Joelle Fritz, our research and strategy specialist responsible for stakeholder relations management, as well as Bianca Dragomir and Tania Zamboni, who are in charge of handling the queries received through the CON-VINCE mailbox and dedicated hotline. Similarly, our multi-disciplinary team encompasses other specialised profiles, including nurses doing a PhD, such as Anne-Marie Hanff. Finally, I am also in close contact with Markus Ollert, Director of the LIH Department of Infection and Immunity (DII), in the context of the diagnostic capacity and large-scale testing work package, as well as with Laetitia Huiart, Director of the LIH Department of Population Health (DoPH), and Manon Gantenbein, Head of the Clinical and Epidemiological Investigation Center (CIEC) at DoPH, in the framework of our collaboration on the Predi-COVID study. This public health situation has further stressed the importance of effective cooperation in achieving meaningful scientific results with concrete health benefits for our patients.

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CON-VINCE study results – second testing phase

CON-VINCE, a national research project aiming to evaluate the prevalence and dynamics of the spread of COVID-19 within the Luxembourgish population, was launched at the beginning of April under the umbrella of the Research Luxembourg COVID-19 Task Force. The second round of testing of the participants in the study (first follow-up after baseline testing) showed a declining infection rate and lower prevalence of the disease, while bringing forward the risk associated with asymptomatic individuals in the context of a second COVID-19 wave.
DECLINING INFECTION RATES

Following the first baseline screening of all participants between mid-April and May 2nd, a second testing exercise took place from May 4th to May 16th as a first follow-up. As part of this phase, all participants were subjected to a second nasal and oropharyngeal swab, followed by a PCR-based analysis to detect the presence of the SARS-CoV-2 virus. During this period, 2 participants out of the entire panel tested positive for the virus, i.e. 0.1%, compared to 0.3% for the first testing round, reporting only mild symptoms. This translates into an estimated 402 infected but asymptomatic or oligosymptomatic (with only mild symptoms) individuals in the Luxembourg population, excluding cross-border workers. “Despite the declining prevalence of the infection, it is important to point out that all the SARS-CoV-2 positive participants in our panel displayed mild or no symptoms and are therefore ‘silent carriers’. This means that they could potentially start new infection chains without knowing it”, explains Prof Rejko Krüger, principal investigator of the CON-VINCE study.

INCREASING ANTIBODY PRESENCE

A serological test was also carried out to detect the presence of antibodies in the blood, which may be an indication of past exposure to the virus. The results showed that 38 participants (2.6%) had antibodies against SARS-CoV-2, compared to 2.09% during the first round of screening. “We noticed an increase in the proportion of participants with antibodies against the virus, although I stress again that the presence of antibodies does not mean that people are immune to COVID-19”, adds Prof Krüger.

ENCOURAGING PARTICIPATION RATE

The participation in the study has also shown positive results, with over 94% of participants of the first testing phase having enrolled for the follow-up round. “We would like to extend our gratitude to all volunteers who renewed their participation in our study. Without their continued motivation and commitment, we would not be able to generate meaningful data and research outcomes for patients and the population in general”, says Prof Krüger. “To keep encouraging enrolment in the upcoming follow-up tests as participants progressively return to work, we will make it possible for them to obtain a certificate of participation in CON-VINCE upon request at the laboratories”, he concludes.

CON-VINCE – MORE THAN JUST INFECTION AND SEROLOGY

In addition to generating data on SARS-CoV-2 infection, CON-VINCE allows participants to make additional key contributions to a variety of related research questions in the context of the COVID-19 pandemic. Namely, the information collected during the study will help answer questions on mental wellbeing, immune response and immunity, infection pathways, the role of the gut microbiome, genetic predisposition and the socio-economic impact of COVID-19. Indeed, CON-VINCE differs from the newly-launched large scale testing (LST) initiative in that it does not aim to simply give a snapshot of the infection status at the time of testing. On the contrary, participants choosing to get tested in the framework of CON-VINCE provide their biological samples for research purposes, in order to support additional studies. For instance, although not compulsory, CON-VINCE participants are strongly encouraged to donate stool samples since SARS-CoV-2 can also be detected through the analysis of faeces. These samples can then be used to perform further analyses as part of other research projects (e.g. detection of the virus in wastewater and elucidation of the role of the gut microbiome composition in determining different susceptibilities to COVID-19).

A MULTIDISCIPLINARY CONSORTIUM

The success of the project relies on the multidisciplinary expertise of its consortium partners, each implicated in different aspects of the multifaceted study. Specifically, the Luxembourg Institute of Health (LIH), the Centre Hospitalier de Luxembourg (CHL), the University of Luxembourg with its Luxembourg Centre of Systems Biomedicine (LCSB), the Luxembourg Institute of Socio-Economic Research (LISER), the Laboratoire National de Santé (LNS) and the Luxembourg Institute of Science and Technology (LIST) contributed to the establishment of the study protocol and setup of the case report form (CRF). TNS Ilres, Laboratoires Réunis, BioneXtLAB and Ketterthill are involved in recruitment and data collection. The LCSB and LIH are involved in data integration and storage. Laboratoires Réunis, BioneXtLAB and Ketterthill are responsible for sample collection, while the Integrated Biobank of Luxembourg (IBBL) ensures sample processing and storage. CON-VINCE is financially supported by the Luxembourg National Research Fund (FNR) and the André Losch Foundation.

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Large-scale testing: FAQ now available

The Research Luxembourg COVID-19 Task Force has created a ‘Frequently Asked Questions’ to address questions regarding Luxembourg’s large-scale testing strategy being rolled out in Luxembourg from 27 May – 28 July 2020.
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Large scale COVID-19 testing: a public health measure

As part of the deconfinement, Luxembourg is calling on its residents and cross-border workers to get tested for COVID-19. It aims to limit the spread of the novel corona virus by voluntary extensive testing until the end of July. This will allow to break infection chains and thus protect family, friends and colleagues. The more tests are carried out, the more new infections can be prevented and the safer everyday life will be.

From 27 May to 28 July 2020, a total of 17 “drive-through” and 2 “walk-through & bike-through” test stations will become available across the country to carry out up to 20,000 tests per day. Citizens and cross-border workers are divided into representative groups that receive invitations by post to get tested voluntarily.

It is important that as many citizens as possible accept these invitations in the coming weeks, because the majority of those infected do not know that they carry the virus. They show little or no symptoms and pass on the virus unconsciously. The COVID-19 PCR test determines whether a person is contagious. While this is a snapshot, it helps identify positive cases, which will then go into domestic isolation for about two weeks and whose contacts are traced back. This reduces the risk of infection for their fellow citizens and new infection chains can be broken. A large-scale participation in the testing increases the protection of their family, friends, colleagues and, last but not least, the risk groups – and thus helps to keep the spread of the virus under control.

Who will be tested and when?

The testing starts already this week: about 6,000 high school graduates and For the large-scale testing, the population is divided into 3 categories depending on their risk of being exposed to the virus:

Category 1 specifically targets groups who are at work most exposed to the virus and who are in contact with many other people, which may increase the risk of transmission. These are professional groups like nursing staff and doctors; hairdresser and cosmetic services; police officers; staff from nurseries; staff from the HORESCA sector as soon as it is reopened; etc.. This category receives invitations to be tested every two weeks.

Category 2 comprises the groups that are either already working normally again, or for which the lockdown will be lifted in the coming weeks. Within these larger groups, small representative subgroups will be tested for the virus. The results from these subgroups can be seen as an early warning signal for the respective sectors, since they allow to identify any new flare-ups in virus spreading at an early stage. Groups for which the lockdown will be lifted can either be tested completely at once (and then be monitored by regularly testing smaller samples) or be split into randomly selected subgroups which are tested over the entire period.

Category 3. Once the exit restrictions are entirely lifted, the timely detection of an increase in infections is crucial to reduce the risk of a second pandemic wave. Therefore, representative samples of the entire population of Luxembourg including cross-border workers are tested every week. This will facilitate the early detection of infection flare-ups in certain regions or sectors, break infection chains and thus help to reduce the spread of SARS-CoV-2.

Based on this concept, the following sectors will be tested:

From 25 May:

  • Sectors from category 1: hairdressing and cosmetics, childcare personnel.
  • Sectors from category 2: construction sector.

From 1 June 2020:

  • Sectors from category 1: nursing staff and doctors, police officers, prison guards, pharmacy personnel, system-relevant sector personnel.
  • Sectors from category 2: elementary school students and teaching staff, industry and retail.

This multifaceted testing strategy covers all potential points at which the virus spread can flare up again. It should allow to test a large part of Luxembourg’s population once and thus help to continuously monitor and keep the spread of the virus under control. This enables all residents and cross-border workers to return to their social and professional life as safely as possible. Considering the dynamics of infections, flexibility is needed to be able to respond quickly to new developments (regional or sector-specific infection clusters). Accordingly, depending on the circumstances, the test capacities can be adapted on a weekly basis.

Where will the testing take place?

A total of 17 drive-through test stations are spread across the country. They are located in Neudorf, Niederanven, Ersange, Frisange, Dippach, Steinfort Windhof, Steinfort P&R, Machtum, Junglinster, Schieren, Schinkert, Luxembourg-Bouillon, Kirchberg, Howald, Bascharage, Belval and Esch-sur-Alzette. In addition, walk-throughs are planned in Belval, Kirchberg and at the Rotonde close to the train station in Luxembourg city. A total of 400 people will be working at these stations in the next two and a half months. These are nurses, security and cleaning staff, administrators, logisticians and coordinators.

Figure 1: Drive-through (blue) and Bike-through/walk-through stations (green) with their maximal testing capacity (red). A) Black dots mark all stations in the whole country. B) Zoom of the Centre and South of Luxembourg.  

How does the testing work?

Citizens and cross-border workers will receive an invitation per post, which will allow them book a test appointment online at one of the testing stations. On the selected date, the person goes to the testing site, where they present their invitation, ID card and their insurance card. A throat swab is then carried out and sent to the laboratory. The tested person leaves the test site and receives the test result via SMS within two days. If the result of the test is positive, the person is contacted personally by the Inspection Sanitaire and will be asked to spend two weeks at home in self-isolation. If the test result is negative, the person must continue to follow the usual protective measures and can return to everyday life.

Who are the partners within this project?

The project has been developed by Research Luxembourg’s COVID-19 Task Force and is led by the Luxembourg Institute of Health. The tests are carried out by its contractual partner Laboratoire Réunis, who is logistically supported by Ecolog.

What is the COVID-19 Task Force?

Efficient measures in the context of the COVID-19 pandemic require close cooperation between research, hospitals and the Government in Luxembourg. For this reason, Research Luxembourg (LIH, LISER, LIST, LNS, Luxinnovation, University of Luxembourg and FNR, under the coordination of the Ministry of Higher Education and Research) has set up the COVID-19 Task Force in order to better implement relevant initiatives. Based on a list of priorities elaborated by ministries and other partners, a number of work packages have been defined, which the COVID-19 Task Force will work on in the coming weeks and months. In cooperation with the government, the COVID-19 Task Force sees its role in providing scientific input to enable the government to work on a fact-based EXIT strategy. To this end, the COVID-19 Task Force is continuously working on updates on the development of the pandemic in Luxembourg and submits concepts and recommendations from a scientific perspective so that they can be incorporated into the political decision-making process.

Communicated by the Luxembourg Institute of Health and Research Luxembourg

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Covid-19 taskforce

First results of the CON-VINCE study

CON-VINCE, a national research project aiming to evaluate the prevalence and dynamics of the spread of the COVID-19 disease within the Luxembourgish population, was launched at the beginning of April under the umbrella of the Research Luxembourg COVID-19 Task Force. Following the successful recruitment and first testing effort of more than 1800 participants over the age of 18, a first publication has now been uploaded on the preprint server medRxiv (Reference: MEDRXIV/2020/092916) and will be soon submitted for peer-reviewed scientific publication.
Low rate of infection but with potential for unnoticed virus spread

All participants already underwent a nasal and oropharyngeal swab followed by PCR-based virus test. The PCR analysis aims to detect the presence of the SARS-CoV-2 virus. Currently, 5 participants (0.3%) out of the whole panel tested positive for the virus, with individuals being asymptomatic or presenting only mild symptoms.

“Based on these very first numbers, we estimate that 1449 people in Luxembourg alone and without taking into account cross-border workers could be currently infected and show no or only mild signs of the disease”, explains Prof. Rejko Krüger, principal investigator of the CON-VINCE study. “Therefore, they could infect others without even knowing it.”

This highlights why there is a need for a large-scale testing strategy. Asymptomatic carriers need to be identified and isolated, ideally before people return to their workplace.

Almost 2% of the population has been in contact with the virus

In addition, participants underwent a serological test which aims to detect the presence of antibodies in the blood. These tests showed 35 participants (1,9%) have IgG antibodies against SARS-CoV-2, indicating that these people may have had contact with the virus during the last weeks.

“It is important to highlight that the presence of antibodies in the blood is not a proof that people are immune,” details Prof. Rejko Krüger. “It is yet unknown how long the antibodies stay in the blood and how effective they are against the virus. A positive serological test is therefore not a guarantee of protective immunity.”

Communication of positive test results to participants

In case of a positive result of either the PCR analysis or the serological test, a medical doctor of the CON-VINCE study will inform the participant as well as their treating physician. To ensure the anonymity of the participants and protection of personal data, the research study was designed so that only the medical doctors of the study team are able to track the participants’ identity and inform participant about test results in the specific and previously defined case that the result is positive.

Hence, if the participants are not contacted by a medical doctor belonging to the CON-VINCE team within two working days or 2 weeks after the visit to the laboratory, it means their PCR analysis or serology test, respectively, were negative. Following up all participants regularly for two months and then after a year will help understand better the prevalence and transmission of the disease as well as the infection rate in Luxembourg’s population.

Screening a statistically representative panel

Volunteers for the CON-VINCE study were recruited within the pool of 18.000 panel members of TNS Ilres which is as representative as possible of the whole population of the Grand Duchy. The study was carefully designed to both meet highest scientific standards and be feasible within the current constraints due to the emergency situation. In order to do that, CON-VINCE focuses on three criteria to select participants: age, gender, and residency.

“In every study design, researchers have to make choices and take them into consideration when interpreting results,” explains Prof. Ulf Nehrbass, spokesperson of the Research Luxembourg COVID-19 Task Force. “Taking further criteria into account would require a significantly larger number of participants. Therefore, other factors such as household composition, social status or lifestyle could not be considered given the time, organisational, and financial framework of the study.”

The exact methodology will be published in scientific journals, and potential limitations will be taken into accounts when analysing the data.

Successful start thanks to a collaborative effort

Setting up and executing such a comprehensive study in such a short time requires a huge team effort and important input from all the parties involved. This would not have been possible without the contribution of more than 1800 volunteers who agreed to participate in the study, the expertise of the Luxembourgish research institutions – the Luxembourg Institute of Health (LIH), the University of Luxembourg and the Laboratoire National de Santé (LNS) – and the input of several partners: Centre Hospitalier de Luxembourg, TNS-ILRES, Ketterthill, Laboratoires Réunis, and BioneXt Lab. The CON-VINCE study has been funded by the Luxembourg National Research Fund (FNR) and the André Losch Foundation.

“The Research Luxembourg COVID-19 task force wishes to express their greatest thanks to all these people who are key in making CON-VINCE a success for their invaluable commitment to the project,” concludes Rejko Krüger. “We are particularly thankful to the more than 1800 volunteers for their effort and continuing support of this longitudinal research study until 2021. Their repeated participation is crucial in understanding how the prevalence and spread of the virus evolves in Luxembourg over time.”

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