Title Promoter Affiliations Abstract "Assessment and follow-up of SARS-Cov-2 infection in pregnant women and neonates." "Kirsten Maertens" "Centre for the Evaluation of Vaccination (CEV)" "The current coronavirus pandemic affects us all. As with all infections, certain subpopulations are morevulnerable to severe disease and even death and require therefore more research. In this pandemic,the elderly and immunologically fragile people are more prone to severe disease. Pregnant women andvery young infants are traditionally also considered as immunologically different from the generalpopulation, certainly in view of infectious diseases. Since little to nothing is known to the scientificworld of this new virus, researchers and health care personnel dealing with pregnant women and theirneonates do have concerns on the risk they run.This project offers a unique opportunity to map the impact of the current pandemic in a vulnerablesubpopulation of the society. The main objective of the project is to quantify the impact of the SARSCoV-2 pandemic in pregnant women and their newborns/infants by assessing the rate of transmission,the overall health, mental well-being, immunological responses and clinical outcomes of clinicallysuspectedand laboratory-confirmed COVID-19 infections in pregnant women and their neonates. Datawill be collected through online questionnaires that will be send to pregnant women at a 2 weekinterval until 8 weeks postpartum. This will enables us to monitor possible COVID-19 infections inpregnancy and to look at possible adverse outcomes in pregnant women, fetuses and neonates. At 12months postpartum, women will be contacted again to look at possible long-term consequences ofCOVID-19 infections in pregnancy on infants. Additionally, pregnant women participating in thesurveillance study will be asked to provide maternal and cord blood samples at delivery to measure theprevalence of SARS-CoV-2 specific antibodies in pregnant women and newborns and to measure thetransplacental transfer of SARS-CoV-2 specific antibodies from mother to infant during pregnancy.Data from this project will be used to formulate evidence-based recommendations on prevention,treatment and vaccination for COVID-19 in pregnant women and neonates. Additionally, this projectwill provide information for policy makers and experts in the field on public health measures andmanagement of pregnant women and neonates during this pandemic." "What can olfactory dysfunction in COVID-19 tell us about the mysteries of the sense of smell?" "Laura Van Gerven" "Allergy and Clinical Immunology Research Group" "For many years, the human sense of smell was considered a “nonessential”sense.With olfactory dysfunction as a prominent and often sole symptom ofCOrona Virus (SARS-CoV-2) Induced Disease (COVID-19), largepatient cohorts continue to experience the impact of postviralolfactory dysfunction on their quality of life. Indirectly, the currentpandemic has renewed interest in the human sense of smell.The mechanisms of olfactory dysfunction in COVID-19 remainentirely unknown.We believe that a comprehensive histological and molecularinvestigation of postmortem tissues of the olfactory system isrequired to get insights into these mechanisms.We propose an innovative study design to obtain bed-side, by anendoscopic endonasal approach, high-quality tissue samples fromthe human respiratory and olfactory system and adjacent brainregions from deceased COVID-19 patients, influenza patients, andcontrols.We will perform immunohistochemistry and in situ hybridizationstaining with commercially available antibodies and RNAscopeprobes for SARS-CoV-2 and markers of various cell types in therespiratory and olfactory mucosa, the olfactory bulb, and adjacentbrain tissue.We hope to achieve insights into (1) the pathophysiologicalmechanisms of postviral olfactory dysfunction, (2) the possiblescenario of the olfactory pathway as entrance to the central nervoussystem and (3) the immune response and regenerative capacity ofthe olfactory mucosa upon viral invasion." "CARE Corona Accelerated R&D in Europe" "Johan Neyts" "Laboratory of Virology and Chemotherapy (Rega Institute), Clinical Pharmacology and Pharmacotherapy" "The Severe Acute Respiratory Syndrome coronavirus 2 (SARS-CoV-2) pandemic has emerged as the largest global health threat to humanity in this century. According to the World Health Organisation Situation Report of March 28th 2020, 571,659 patients were  diagnosed with Coronavirus Disease 2019 (COVID-19) and 26,493 deaths were reported globally. The wide spectrum of clinical symptoms, disease severity in high risk individuals, transmission efficiency and high mortality, raises an immediate need for vaccines or therapeutics. Given that the viral variant is new in the human population and emerged less than 4 months ago, there is no vaccine or approved therapies. The Corona Accelerated R&D in Europe (CARE) consortium is a coalition of 37 globally renowned academic institutions, pharmaceutical companies and non-profit research organizations who have committed to rapidly and efficiently address this emergent health threat, and the main objectives are: the development of therapeutics (i) to provide an emergency response towards the current COVID-19 pandemic by drug repositioning and (ii) to address the current and/or future coronavirus outbreaks by broad-spectrum small-molecule drug discovery and/or virus-neutralizing antibody discovery. To achieve this, a collection of repurposed drugs, focused libraries and small molecule libraries will be screened against SARS-CoV-2, other emerging SARS-CoV-2 clades and related coronavirus genera in phenotypic or target-based assays. A focused medicinal chemistry campaign will identify small-molecule hits, and Absorption, Distribution, Metabolism and Excretion (ADME), pharmacokinetic/pharmacodynamic (PK/PD), potency and safety of these therapeutic candidates will be assessed in vitro and in animal models. Virus-neutralizing monoclonal antibodies will be generated and further characterized. Immune markers will be identified contributing to the host immune responses to SARS-CoV-2 infections, and the correlation with clinical and virological outcomes will be determined. Finally, lead candidates will be advanced into Phase1 and Phase 2 clinical trials in humans. With this reactive response, the CARE consortium is dedicated to win the fight against coronavirus." "COVID19 Immune Repertoire Sequencing" "Laurent Ratsarahery, Koen Vercauteren" "Department of Clinical Sciences, Management, Clinical Virology" "A pneumonia of unknown cause detected in Wuhan, China was first reported to the WHO on December 31st 2019. One month later, the outbreak was declared a Public Health Emergency of International Concern. Today, we have reached over 1.000.000 confirmed cases worldwide, of whom just under 100.000 did not survive the infection, now known as SARS-CoV-2 causing COVID-19 disease (WHO Situation Report – April 9th, 2020). This pandemic SARS virus is the third in 20 years’ time to emerge (SARS‐CoV in 2002, MERS‐CoV in 2012). These viruses belong to the Coronavirinae subfamily of the Coronaviridae family. Since these periodically emerging Coronaviruses spread rapidly and induce serious infectious pulmonary diseases, they pose a continuous human health threat. Once, hopefully, the current pandemic has been controlled, it is speculated that SARS-CoV-2 can re-emerge during the following respiratory infectious seasons [1]. This advocates for the swift development of an effective SARS-CoV-2 vaccine. Although these efforts are currently ongoing [2], information on immunologic responses during natural infection -essential for vaccine design- is scarce. Some experience has been gained from earlier Coronavirus outbreaks indicating that the immune response is essential to control and eliminate CoV infections [3, 4]. However, immunopathology might result from unbalanced immune responses leading to impaired disease outcomes.Recently, high-throughput sequencing of T- and B cell receptor variable region genes (T- and BCRseq) has revolutionized cellular adaptive immune repertoire mining [5]. In-silico tools can be used to organize these datasets into cell clusters based on T/BCR sequence and physicochemical similarities[6-8]. These similarities indicate common epitope recognition. Investigating these cell clusters 1) within one patient (longitudinal analysis of clonal immune cell expansion) and 2) between different patients known to suffer from the same infection -such as the SARs-CoV-2 viral outbreak- could allow identification of antigen-specific T- and B cells important to combat this infectious disease (COVID-19)." "Connecting European Cohorts to Increase Common and Effective Response to SARS-CoV-2 Pandemic (ORCHESTRA)." "Samir Kumar-Singh" "Laboratory of Medical Microbiology (LMM), University Hospital Cologne, Ludwig-Maximilians University Munich, Stuttgart University, Andalusian Health Service, Veneto Region, Barcelona Institute for Global Health, University Medical Center Groningen, University of Verona, Institut National de la santé et de la recherche médicale (INSERM), CINECA, Fondation Congolaise pour la Recherche Médicale, Emilia-Romagna Region-Health Agency and Regional Social Security, National Institute of Public Health, Heidelberg University Hospital, Luxembourg Institute of Health, University of Bologna, Lambaréné Medical Research Centre, Assistance Publique Hôpitaux de Paris, National Computer Center for Higher Education, PENTA Foundation, Helmholtz Centre München, University of Buenos Aires, University of Oviedo, Charité University Medicine Berlin, Laboratory of cell biology and histology" "The ORCHESTRA project provides an innovative approach to learn from the SARS-CoV-2 health crisis and derive recommendations for increasing preparedness for future outbreaks. The main outcome of the project is the creation of a new pan-European cohort built on existing and new large-scale population cohorts in European and non-European countries. Data analysis through a federated learning technique supported by advanced modelling capabilities will allow the integration of epidemiological, clinical, microbiological and genotypic aspects of population-based cohorts with environment and socio-economic features. The ORCHESTRA cohort will include SARS-CoV-2 infected and non-infected individuals of all ages and conditions and thereby enabling a retrospective evaluation of risk factors for the disease acquisition and progression of the disease and prospective follow-up aimed at exploring longterm consequences and analysis of vaccination response when vaccines will be available. To better address these research questions, the ORCHESTRA-cohort will include adequately sampled representatives of general populations, COVID-19 patients and special 'at risk' populations of fragile individuals and health-care workers. The project will assess also health costs of COVID-19 with special emphasis on delayed health services in the fragile populations. The participation of non-European and Low-Medium Income Countries and a Global COVID-19 Guidance group of major stakeholders and investigators from successful clinical trials addressing therapeutic approaches to COVID-19, ensures inclusion of all expertise needed and translation of recommendations to different social and economic settings. The project will significantly impact on the responsiveness to SARS-CoV-2 and can be used as a model for responsiveness for new public health threats. Specifically, in this work package, different cytokines and chemokines from blood of COVID-19 patients will be studied and markers predicting disease severity, mortality, and/or long term sequalae will be identified in collaboration with other partners of ORCHESTRA." "Monitoring SARS-CoV-2-specific immunity upon COVID-19 vaccination in nursing home residents and staff" "Piet Cools" "Department of Diagnostic Sciences" "Nearly 60% of all COVID-19 deaths in Belgium so far were nursing home (NH) residents. Therefore, in January 2021, Belgium prioritised NH residents and staff for vaccination with the Pfizer-BioNTech (PB) vaccine in the COVID-19 vaccination campaign. The PB vaccine showed 95% efficacy in a phase III trial, but older people were largely underrepresented. This is worrisome, since older adults most often suffer from immunosenescence (decreased immunity), frailty and comorbidities, all of which are strongly related with decreased responses upon vaccination targeting other infections. Additionally, it is unclear whether COVID-19 vaccination will offer sufficient protection against the emerging SARS-CoV-2 variants of concern. Therefore, our overall aim is to monitor PB-vaccine induced immune responses and clinical protectiveness in nursing home residents and staff. The proposal is embedded within a large-scale national COVID-19 epidemiological study in nursing homes that started in February 2021. In NH residents and staff, we aim (i) to use capillary blood collected on paper cards (ie. dried blood spots), currently being collected, to monitor the level of neutralising antibodies; (ii) to evaluate the level of protection after vaccination against the emerging SARS-CoV-2 variants in real-time using in-house pseudoneutralisation assays; (iii) to document incident COVID-19 cases and correlate these with antibody levels and to (iv) investigate cellular immunity in non-responders." "Connecting European Cohorts to Increase Common and Effective Response to SARS-CoV-2 Pandemic (ORCHESTRA)." "Surbhi Malhotra" "University Hospital Cologne, Ludwig-Maximilians University Munich, Stuttgart University, Andalusian Health Service, Veneto Region, Barcelona Institute for Global Health, University Medical Center Groningen, University of Verona, Institut National de la santé et de la recherche médicale (INSERM), CINECA, Fondation Congolaise pour la Recherche Médicale, Emilia-Romagna Region-Health Agency and Regional Social Security, National Institute of Public Health, Heidelberg University Hospital, Luxembourg Institute of Health, University of Bologna, Lambaréné Medical Research Centre, Assistance Publique Hôpitaux de Paris, National Computer Center for Higher Education, PENTA Foundation, Helmholtz Centre München, University of Buenos Aires, University of Oviedo, Charité University Medicine Berlin, Laboratory of Medical Microbiology (LMM)" "The ORCHESTRA project provides an innovative approach to learn from the SARS-CoV-2 health crisis and derive recommendations for increasing preparedness for future outbreaks. The main outcome of the project is the creation of a new pan-European cohort built on existing and new large-scale population cohorts in European and non-European countries. ORCHESTRA aims to perform in-depth laboratory based assays on samples collected from Covid-19 patients during acute phase and during long-term sequelae as well as follow-up individuals post-vaccination. University of Antwerp laboratories are studying viral variants and the respiratory microbiome dynamics (Surbhi Malhotra) as well as analyzing the humoral and cell-mediated immune responses and cytokinome profiles (Samir Kumar -Singh). The laboratory analysis workpackage also aims to understand the role of human genetics, epigenetics and of the gut microbiome in disease pathogenesis and prognosis. This large consolidated wet-lab WP is led by the University of Antwerp. The project is funded by the European Union's Horizon 2020 research and innovation programme under the ERAvsCORONA Action Plan developed jointly by Commission services and national authorities." "Acquired immunity and immunologic aspects of SARS-CoV-2 infection a population of patients and healthcare workers in Multidisciplinary Oncologic Centres. (MOCOR-Study)." "Peter Van Dam" "Proteinchemistry, proteomics and epigenetic signalling(PPES), Center for Oncological Research (CORE)" "COVID-19 is a disease caused by an infectious outbreak of the SARS-CoV-2 virus. Today, the virus is widely spread throughout the world and declared by the World Health Organisation (WHO) as a pandemic. There are a broad range of clinical presentations of a SARS-CoV-2 viral infection varying from asymptomatic, sensation of a mild cold or flu to severe bilateral pneumonia and death. The mortality is the highest in the elderly and in people with a pre-existing condition such as cancer. In addition, it has already been shown that in patients with a severe COVID-19 infection the cytokine levels in the blood are very high, which can lead to organ failure. Since in cancer patients cytokine production is already increased by their disease and by treatment, this implies a higher susceptibility to develop severe COVID-19 when an exaggerated immune response to this virus produces even more cytokines (""cytokine storm""). The aim of this project is to be able to detect preventively when there is a risk of developing a ""cytokine storm"" so that potential therapy such as cytokine inhibitors can be used. To accomplish this, the response of the immune system to SARS-Cov2 infection will be mapped in this project. This will be done by performing immunological tests on blood samples from cancer patients and a healthcare workers the same oncology units who seropositive for the SARS-CoV-2 infection. Both blood samples from symptomatic and asymptomatic COVID-19 subjects will be examined immunologically. The immunological tests include immunoassays, flow cytometry and immunomethylomics. The collection of blood samples has already started at the end of March 2020 and the inclusion period is 3 months, so that the early phase, the peak phase and the foreseen decline of the pandemic are included. Cancer patients are asked to take additional blood samples during routine blood samples. A monthly blood sample is requested from the group of healthcare workers (4 samples per participant). First of all, the seropositive samples will be detected on the basis of a serological test. These results also provide insight into the proportion of infected high-risk patients in a hospital environment. On the basis of the immunological tests, the immune response will be compared between the symptomatic cancer patients and asymptomatic cancer patients and matched controlled healthcare workers. In this way, immunological risk factors for the development of severe COVID-19 can be identified and a new outbreak can be controlled in a scientifically responsible manner." "“Design and synthesis of inhibitors of the SARS-CoV-2 main protease based on the 1,2,3-triazole scaffold”" "Mario Alfredo Quevedo, Wim Dehaen" "Sustainable Chemistry for Metals and Molecules" "This project is focused towards obtaining new chemical entities with potential application to the pharmacological management of COVID-19 disease, pathology caused by infection with the SARS-CoV2 virus. The rapid worldwide spread of this disease has outlined the high priority of scientific efforts towards the discovery and obtaining of new therapies based on small molecule drugs, complementing the effectiveness of vaccines approved to date. In this context, this project contributes to the field of knowledge with a multidisciplinary effort aimed to the discovery and obtaining of potential inhibitors of the main protease (MPro) of SARS-CoV2, a validated therapeutic target for the treatment of COVID-19. Current state of the art analyses demonstrates and increasing scientific interest in this kind of molecules, including both reversible and irreversible (targeted) covalent inhibitors. In this context, it is worth mentioning that by the end of December 2021, the U.S. Food and Drug Administration issued an emergency authorization for the use of Nirmatrelvir , the first MPro inhibitor approved for oral treatment of COVID-19. This breakthrough demonstrates the feasibility and public health concern towards the discovery of new MPro inhibitors. The novelty of the project lies in the use of the 1,2,3-triazole scaffold as a biososteric replacement of the peptidic bond, which is present in this type of peptidomimetic drugs. Consequently, the research hypothesis states: 'By replacing the peptidic bond present in MPro inhibitors by a 1,2,3-triazole scaffold, it is possible to design highly potent and selective drug candidates, conferring also optimized biopharmaceutical properties that may constitute benefits throughout their drug development pipeline'. In this way, and as will be further detailed in the following sections, the present project encompasses a modern and multidisciplinary approach to the obtaining of new chemical entities of pharmaceutical interest for the treatment of COVID-19." "The performance of saliva specimens for the molecular detection of SARS-CoV-2 and a saliva pooling strategy as a diagnostic tool for epidemiological studies in current SARS-CoV-2 pandemic." "Piet Cools" "Department of Internal Medicine and Pediatrics, Department of Translational Physiology, Infectiology and Public Health, Department of Veterinary Public Health and Food Safety, Department of Diagnostic Sciences" "Nasopharyngeal swabs are recommended for the molecular diagnosis of COVID-19 but offer disadvantages such as dire shortage. Therefore, we aim to validate saliva as an alternative specimen. We further plan to design a saliva pooling strategy as a part of a diagnostic tool for largescale real-time epidemiological testing. Such strategy will be of value in the management of current pandemic."