7 projects

Understanding Immunity in COVID-19

Previously developed model of immune response [Abulikemu et al 2020] will be modified in the collaboration with model authors and used for understanding processes involved in SARS-CoV2. We will develop a systems immunology tool that stratifies the coronavirus patient population according to (i) their likelihood of developing the cytokine tornado and (ii) the tornado subtype they are subject to. It will insert individual patient information into our Abulikemu et al model [2020] and compute the implications for whether or not a flip from moderate ('acute') inflammation to a 'cytokine tornado...

Functional characterization of COVID-19 patient gut microbiome

While COVID-19 is mainly considered an airway and lung disease, up to 79% of patients present with gastrointestinal symptoms and recent studies report on the presence of SARS-CoV-2 viral RNA and particles in stools of infected patients, suggesting that the gastrointestinal (GI) tract may have a more important role in disease pathology or transmission than previously thought. The GI tract is also the site of the dense and diverse microbiome, which has the ability to regulate intestinal and systemic immunity through the conversion of dietary nutrients into bioactive metabolites. Consequently,...

A PRECLINICAL EVALUATION: VACCINATION AND EFFICACY AGAINST SARS-CoV-2

SARS-CoV-2, the causative factor of COVID-19, is endangering the world's health, prosperity and political crises are on the horizon. Nations worldwide had to take drastic measures to prevent catastrophes: strict confinement and hygienic measures have been undertaken to minimize the virus spread. Despite the control measures, the pandemic is inevitably damaging the economy due to a shutdown of public and business life, an overload of the healthcare systems, and the high case fatality rate of COVID-19. The global fight against COVID-19 has mobilized, and many provisional treatments are being ...

COVID-19 and Neurturin

SARS-Cov-2 is a coronavirus is at the origin of the current COVID-19 pandemic, which poses a global and significant threat to public health worldwide. Although several treatment modalities have been evaluated, none has allowed a therapeutic breakthrough until now. New treatment modalities are therefore urgently needed. We have previously described that neurturin, a member of the glial cell line-derived neurotrophic factor family, expressed not only as a growth factor in the nervous system but also the immune system, displays clear anti-inflammatory properties in mouse asthma models. Indeed,...

Screening for small molecule activators of mesenchymal stem cells as potential therapeutics for C...

Some COVID-19 patients have been successfully treated with mesenchymal stem cells. Most probably, the positive effect comes from the immunomodulatory function of mesenchymal stem cells on the inflammatory burst in the virus-damaged alveolar region. An already established 3D in vitro model representing the alveolar barrier will be enriched with mesenchymal stem cells to further increase the similarity to the human in vivo situation. We suggest to use these alveolar models as a tool to screen for small molecules that activate endogenous mesenchymal stem cells and that have therefore therapeut...

MicroRNA biomarkers of COVID-19 severity

The Cardiovascular Research Unit of LIH proposes to apply its know-how on RNA biomarkers to identify circulating microRNAs (miRNAs) able to predict COVID-19 severity. This project is included in COVID-19 Task force WP02 and aims to fulfill the medical need of identifying patients at high risk of developing complications after infection by SARS-CoV-2 virus. The discovery of novel prognostic biomarkers will help tailoring healthcare to each individual for patient's benefit. Considering the importance of the inflammatory storm on disease severity and patient outcome, we will focus on inflamma...

HUMAN GENETIC VARIANTS AS PREDICTORS OF THE IMMUNE RESPONSE TO COVID-19

One of the main unanswered questions is why some individuals infected with COVID-19 develop severe disease, whilst others do not. Current evidence suggests that genetic variations influence human immune reactions to microbial infections, including both innate and adaptive immune responses. Here, we aim to evaluate the impact of genetic factors on the variability of the innate immune response to SARS-CoV-2 infection. On top of a large screening of the classical immune response genes (e.g. IFNs, ILs, TLRs, MHCs), we are particularly interested in the IRG1/ACOD1 gene, which we previously di...

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