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Mechanisms

A. Marchant - S. Goriely - N. Dauby - S. De Wit - O. Vandenbergh - C. Montesino - V. Mascart - V. Del Marmol - A. Le Moine - F. Andris - C. Gueydan - A. Botteaux - A. Matagne

ULB, CHU Saint-Pierre, Hôpital Erasme, ULiège - FNRS

" The project investigates the immune responses to SARS-CoV-2 infection in humans. Cohorts of patients and contacts are recruited and followed-up during several months following infection. Using systems serology and systems biology approaches, the quality and dynamics of antibody and cellular responses are analysed to identify correlates of protection against severe disease and to determine the duration of natural immunity to the virus. The project should provide insight in the host response to SARS-CoV-2 and should help define deconfinement strategies and develop prophylactic and therapeutic interventions against COVID-19. "
Funding: COVID 19 - ULB
Contact: Arnaud Marchant: This email address is being protected from spambots. You need JavaScript enabled to view it. Stanislas Goriely: This email address is being protected from spambots. You need JavaScript enabled to view it.

Ahmad Awada, Chef de Service, Medical Oncology - Karen Willard-Gallo, Laboratory Head, Molecular Immunology - Aspasia Georgala, Infectious Disease Physician - Maher Khalife, Chef de Service, Anesthesiology- Alain Roman, Chef de Service, Intensive Care

ULB, Bordet Institute and CHU Saint-Pierre
" The limited capacity of intensive care unit (ICU) beds and the high mortality of patients requiring ICU care after COVID-19 infection are major problems that urgently require solutions. Early evidence suggests that an individual patient's immune responses to this virus are a key factor in their disease pathogenesis. This response can be further compounded by underlying factors, which for patients at Bordet can be exacerbated by their cancer status. A recent study shows that some cancer patients (particularly lung, blood or metastatic cancer patients) are three times more likely to die from COVID-19 infection. Thus, there is an important need to understand and identify immune biomarker(s) that measure functionality of innate and/or adaptive immunity in the blood with rapid turnaround to provide much needed information for clinical decision making. The anticipated results of this collaborative research project include the identification of...

André Matagne, Alain Brans, Marylène Vandevenne, Maximiliano Figueroa, Moreno Galleni, Romain Malempré

ULiège - Royal Academy of Sciences, Letters and Fine Arts of Belgium
"The Centre for Protein Engineering (CIP, ULiège), through its two technological platforms, has been involved in the production of reagents (i.e. proteins) for diagnostic and analyses of SARSCoV-2 infection. In particular, Protein Factory has produced a pure and highly active enzyme (CAS12) for a CRISPR/CAS assay, which, in combination with classical PCR technology allows rapid detection of the virus. Automated screening is currently performed at Robotein for optimal formulation of CAS12. The production of complementary protein reagents for such tests is underway. Furthermore, in a collaborative effort with Dr Arnaud Marchant at Institut d'Immunologie Médicale (ULB), the CIP is involved in the design and production of recombinant SARS-COV-2 antigens towards the development of a platform for high dimensional systems serology analysis of SARS-CoV-2 antibodies."
Contact: André Matagne This email address is being protected from spambots. You need JavaScript enabled to view it. 

Caroline Huart, MD, PhD - Bernard Hanseeuw, MD, PhD - Valérie Hox, MD, PhD - Pascal Kienlen-Campard, PhD- Vincent Van Pesch, MD, PhD

UCLouvain and Cliniques universitaires Saint-Luc - FNRS
" Anosmia has been reported to be a major symptom of COVID-19. Since high viral loads are found in the nasal cavity of patients and since single-cell analyses found that olfactory sustentacular and stem cells highly express ACE2 and TMPRSS2, it is suspected that cells of the olfactory neuroepithelium are a preferred target of the virus. Some COVID-19 patients present with neurological symptoms. Interestingly, it has been reported that the former SARS-CoV, can ascend intracranially, possibly via the olfactory nerves. Since olfactory receptor neurons form a direct connection between the nasal cavity and the brain, we hypothesize that these cells act as a gateway towards the brain in some patients. The main aims of the projects are (1) to investigate the pathophysiology of COVID-related olfactory dysfunction and (2) to investigate whether olfactory receptor neurons could be the entry site of SARS-CoV2 to the brain. "
Funding...

Charles Nicaise, Professor

UNamur
" In vitro studies will investigate the abilities of SARS-Cov-2 to enter various types of human neurons (cell lines and iPS-derived) and possible axoplasmic transport. In the meantime, analysis of post-mortem CNS and PNS samples from COVID patients would strengthen the hypothesis of SARS-Cov-2 neuro-tropism. "
Funding: CUR-FNRS (pending)
Contact: This email address is being protected from spambots. You need JavaScript enabled to view it.

Charles Pilette, Professor

UCLouvain, St-Luc
" We aim to characterize the reprogramming of structural cells of the lungs that are direct targets of the SARS-CoV-2, namely type 2 alveolar epithelial cells and endothelial cells, as well as their potential role in the induction of the (hyper)inflammatory phase of the disease leading to acute lung injury. The skills of our laboratory in lung and mucosal immunology research that are relevant to this field are (1) access to precious human lung tissue (e.g. from SARS-CoV-2 patients), (2) multiplex immunofluorescence staining and isolation of structural cells (e.g. alveolar epithelial cells, endothelial cells) from the human lung, as well as (3) their characterization using cell culture-based readouts and (in collab. with the UCL-CTMA) genetic sequencing. "
Funding: FNRS CUR, application submitted on 01-05-20.
Publication References: 1. Gohy ST, Hupin C, Fregimilicka C, Detry BR, Bouzin C, Gaide Chevronay H, Lecocq M, Weynand B, Ladjemi MZ, Pierreux CE, Birembaut P...

Daniel Desmecht, Professor - Mutien Garigliany, Professor

FARAH - ULiège 
" We are describing the evolution of the respiratory function after infection using whole-body plethysmography in a hamster model of SARS-CoV-2 pneumonia. Although the tropism of the virus for the upper respiratory tract is well documented, little is known about the pathophysiological mechanisms involved in the impairment of the respiratory function and the development of acute respiratory distress syndrome (ARDS) in some patients. There is a critical need for the development of noninvasive evaluation tools of the respiratory function over the disease course in order to develop therapeutic strategies aiming at specifically improving this function. Plethysmography is a noninvasive method allowing the quantitative evaluation of the lung volume and function. The selected plethysmographic parameters will allow a noninvasive monitoring of the lung function and lesions in the hamster model, permitting the screening of therapeutic molecules aiming at alleviating the...

Daniel Desmecht, Professor - Mutien Garigliany, Professor

FARAH - ULiège 
" We recently showed that domestic cats can be spontaneously infected by SARS-CoV-2 and develop transient, yet severe, pneumonia. Similar reports in other countries confirmed the susceptibility of cats, ferrets, lions and tigers to the infection. Dogs can get infected but, apparenlty, subclinically. Beside the importance of these findings for veterinarians and animal health, a series of domestic or wild animal species might constitute a reservoir of SARS-CoV-2 and dramatically complicate the "uncontainment" process. Domestic cats, minks, ferrets, hamsters, dogs, tigers and lions were all shown to be naturally or (for some species) experimentally susceptible to SARS-CoV-2 infection. In addition, cats, minks, ferrets and hamsters were shown to be able to efficiently transmit the virus to in-contact animals. Little is known about the actual host range of the virus. It is critically needed to determine which domestic, peri-domestic (especially rodents) and wild animals can...

Didier Serteyn, Professor - Justine Ceusters, CSO RevaTis - Charlotte Sandersen, Professor

ULiège and RevaTis SA (Spin Off)
" The project aims to assess the effects of muscle derived stem cells on a preclinical model of acute respiratory distress syndrome induced by a perfusion of endotoxins. We focused on the modulation of neutrophil excessive activation. RevaTis developped a GMP production of muscle derived Mesenchymal Stem Cells and is authorized to produce clinical batches. The IPCLab (Liege University) developed an ARDS model in pigs. We aim to demonstrate a reduction of the ARDS severity, a reduction of the cytokines storm and a modulation of the excessive activation of neutrophils observed in ARDS. "
Funding: Research grants from Ulg (POC) and FNRS (CURE) are pending. RevaTis supplies muscle derived Stem Cells for R&D projects
Publication References: Sci Rep. 2017 Apr 6;7(1):696. doi: 10.1038/s41598-017-00803-7. From skeletal muscle to stem cells: an innovative and minimally-invasive process for multiple species. Ceusters J, Lejeune JP, Sandersen C, Niesten A...

Fabrice JOURNE, Doctor - Alexandre LEGRAND, Professor - Jean-Marie COLET, Professor

UMONS 
" Development of a Covid-19 serum library within the UMONS biobank. Collection and storage of samples (serum, blood or urine samples as well as nasopharyngeal samples) from patients diagnosed with Covid-19 positive or negative by an RT-PCR test. Collaboration between UMONS and Ambroise-Paré hospital (Mons) as well as Epicura hospital network (Baudour, Hornu). "
Funding: UMONS logistic and fiinancial supports
Contact: UMONS Biobank Prof. A. legrand, Manager Dr. F. Journe, Coordinator

Florence SCHLEICH, MD, PhD

ULiege, CHU, GIGA I3
" Are obstructive diseases risk factors for developing pulmonary complications due to COVID19? We will include all patients followed up at CHU of Liege for COVID19 infection and classify them according to their underlying bronchopulmonary disease. The aim is to evaluate if asthma, severe asthma or chronic obstructive pulmonary diseases represent risk factors for developing pulmonary complications during COVID 19 infection. We want to find out biological or clinical predictors of complications. We also want to evaluate efficacy and safety of inhaled corticosteroids in asthma in case of COVID infection. Biomarkers will be measured at baseline and during follow-up. "
Funding: Fonds Leon Frederic
Contact: Schleich Florence, MD, PhD This email address is being protected from spambots. You need JavaScript enabled to view it. This email address is being protected from spambots. You need JavaScript enabled to view it.

François Dufrasne, Dr. - Benoit Kabamba-Mukadi, Pr.

UCLouvain
" This study aims to assess the potential roles of spike glycoproteins and viral proteins encoded by ORF6, ORF7a, ORF8 and ORF10 in the antagonism of several known restriction factors (BST-2, GBP5, IFITM, ...) and in the modulation of innate immune responses (NF-kB pathway and IFN response). These proteins will be expressed in different cell models and we will define their ability to bind and/or degrade restriction factors. Depending on results, we will perform sequencing (NGS) of these genes from clinical isolates in order to observe whether the genetic variability can be linked to the pathogenesis of SARS-CoV-2 viruses. "
Funding: Own funds
Contact: This email address is being protected from spambots. You need JavaScript enabled to view it.

Francois Mullier, Prof - Alain Dive, Prof - Michael Hardy, Dr - Sarah Lessire, Prof - Isabelle Michaux, Prof - Jonathan Douxfils, Prof

UCLouvain, CHU UCLouvain/UNamur
" Evaluation of the thrombotic risk associated with SARS-CoV-2 infection and its management in the intensive care unit: a clinical and biological longitudinal study. Background Since the beginning of SARS-CoV-2 outbreak in December 2019, data accumulate regarding the high thrombotic risk associated with this infection, which could explain substantial part of the observed morbidity and mortality (1). Accordingly, a retrospective study suggested that prophylactic anticoagulation could reduce mortality in severe COVID-19 patients with sepsis-induced coagulopathy (2). Furthermore, a European cohort reported a 27% incidence of venous thrombo-embolisms (VTEs) despite systematic prophylactic anticoagulation, raising the question whether deeper anticoagulant regimen would be beneficial in severe COVID-19 (3). Some authors also suggested that fibrinolysis alterations could be a significant determinant of SARS-CoV-2 infection's prognosis, as it is in...

Frédéric Silvestre, Professor

UNamur
" The main scientific question of this project aims to understand this inter-individual variability in the response to 2019-nCoV in human population, first during ageing process, second among population of same age. The first hypothesis that will be tested in this project is that epigenetic differences among human population can, at least partly, explain differences in the individual responses to SARS-CoV-2, and that this virus differentially affects the epigenome of different individuals during the infection. The second hypothesis that will be tested is that changes in the epigenome during ageing could increase the susceptibility of patients to SARS-CoV-2. "
Funding: To be searched
Publication References: - Fellous A, Earley RL, Silvestre F. Identification and expression of mangrove rivulus (Kryptolebias marmoratus) histone deacetylase (HDAC) and lysine acetyltransferase (KAT) genes. Gene, 691 (2019), 56-69. - Fellous A, Earley RL, Silvestre F. The Kdm/Kmt gene families in...

Gilles Parzibut, Doctor

ULiège, CHU
" La recherche de biomarqueurs fiables, sensibles et peu invasifs est un enjeu de premier ordre pour la médecine moderne. En effet, ces biomarqueurs ont le potentiel de transformer la prise en charge médicale en améliorant le dépistage et le diagnostic, mais aussi en permettant de mieux appréhender la physiopathologie d'une pathologie ou sa réponse à un traitement donné. Fort de nos travaux précédents, nous proposons de réaliser une étude prospective sur une population adulte souffrant d'un SDRA modéré à sévère post SARS-COV2 afin de caractériser une signature exosomique plasmatique propre à cette population. "
Funding: FLF FIRS CHU de Liège
Publication References: hankar-Hari, M., Fan, E. & Ferguson, N. D. Acute respiratory distress syndrome (ARDS) phenotyping. Intensive Care Med. (2018). 45;(4): 516-519. Thompson BT, Chambers RC, Liu KD. Acute Respiratory Distress Syndrome. N Engl J Med. 2017;377(6):562–72. Johnstone RM, Adam M, Hammond JR, Orr L, Turbide C. Vesicle...

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Brussels & Wallonia against COVID19