Project description
The determinants of SARS-CoV-2 exposure manifestation
Clinical manifestations of SARS-CoV-2 exposure present great variability, which can partly be explained by comorbidities. Recent evidence indicates that inborn errors of immunity or the presence of autoantibodies are associated with COVID-19 pneumonia. The EU-funded UNDINE project aims to extend such evidence and provide information on the genetic and immunological basis of variations in clinical manifestations following SARS-CoV-2 exposure. The project is a collaborative translational research effort among different European partners, who will contribute resources, including data, from patient cohorts. Moreover, they will develop diagnostic tests for autoantibodies as a means to predict COVID-19 adverse effects.
Objective
"The consequences of SARS-CoV-2 exposure range from a lack of infection to lethal COVID-19. This immense inter-individual clinical variability is the key scientific and medical enigma in the field. While age and certain co-morbidities are known to influence disease outcome, these parameters do not explain all variation. In addition, there are other SARS-CoV-2 phenotypes of clinical importance: multisystem inflammatory syndrome in children and adults (MIS-C/A), and longCOVID. An important breakthrough to unravel the pathogenesis of COVID-19 came from our two Science papers that were recognized by Nature among the top 10 discoveries of 2020. We found that about 4% of patients with critical COVID-19 pneumonia had inborn errors of immunity (IEI) that impair TLR3- and IRF7-dependent type I interferon (IFN) immunity and at least 10% of the patients carried pre-existing autoantibodies (auto-Abs) neutralizing type I IFNs. These findings pave the way for further studies of COVID-19 pneumonia and other SARS-CoV-2 infection phenotypes and form the basis of the present research proposal, UNDINE, which follows a ""bed side to bench"" and ""bench to bed side"" approach, with the following objectivies i) to decipher the genetic and immunological basis of the various SARS-CoV-2 disease manifestations, to identify individuals at increased risk of critical COVID-19, post-infectious immunological complications, and vaccine failure iii) to develop ready-to-use diagnostic tests for large-scale detection of auto-Abs to type I IFNs and propose novel preventive and therapeutic approaches, based on the pathogenesis of SARS-CoV-2 infection for translation into personalised medicine. To achieve these goals, our project will coordinate a European multidisciplinary and translational research effort relying on a strong and synergistic combination of assets, including unique cohorts from 11 EU countries and state-of-the art human genetic, immunological and virological expertises and technologies."
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Keywords
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Funding Scheme
HORIZON-RIA - HORIZON Research and Innovation ActionsCoordinator
8000 Aarhus C
Denmark
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Participants (18)
75654 Paris
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75724 Paris
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3000 Leuven
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00133 Roma
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20132 Milano
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08007 Barcelona
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Legal entity other than a subcontractor which is affiliated or legally linked to a participant. The entity carries out work under the conditions laid down in the Grant Agreement, supplies goods or provides services for the action, but did not sign the Grant Agreement. A third party abides by the rules applicable to its related participant under the Grant Agreement with regard to eligibility of costs and control of expenditure.
08916 Badalona Barcelona
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Legal entity other than a subcontractor which is affiliated or legally linked to a participant. The entity carries out work under the conditions laid down in the Grant Agreement, supplies goods or provides services for the action, but did not sign the Grant Agreement. A third party abides by the rules applicable to its related participant under the Grant Agreement with regard to eligibility of costs and control of expenditure.
08035 Barcelona
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Legal entity other than a subcontractor which is affiliated or legally linked to a participant. The entity carries out work under the conditions laid down in the Grant Agreement, supplies goods or provides services for the action, but did not sign the Grant Agreement. A third party abides by the rules applicable to its related participant under the Grant Agreement with regard to eligibility of costs and control of expenditure.
08908 L'Hospitalet De Llobregat
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3584 CX Utrecht
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51005 Tartu
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17177 Stockholm
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37077 Gottingen
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28046 MADRID
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69280 Marcy l'Etoile
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115 27 Athina
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D02 CX56 DUBLIN 2
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8200 Aarhus
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Partners (3)
Partner organisations contribute to the implementation of the action, but do not sign the Grant Agreement.
Participation ended
1011 Lausanne
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Partner organisations contribute to the implementation of the action, but do not sign the Grant Agreement.
SW7 2AZ LONDON
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Partner organisations contribute to the implementation of the action, but do not sign the Grant Agreement.
1015 Lausanne
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