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The human genetic and immunological determinants of the clinical manifestations of SARS-CoV-2 infection: Towards personalised medicine

Description du projet

Les facteurs déterminants des manifestations liées à une exposition au SRAS-CoV-2

Les manifestations cliniques de l’exposition au SRAS-CoV-2 présentent une grande variabilité, qui peut s’expliquer en partie par les comorbidités. Des données récentes laissent entendre que les erreurs innées d’immunité ou la présence d’auto-anticorps sont associées à la pneumonie COVID-19. Le projet UNDINE, financé par l’UE, entend rassembler d’autres preuves de ce type et fournir des informations sur les bases génétiques et immunologiques des variations des manifestations cliniques à la suite d’une exposition au SRAS-CoV-2. Le projet est un effort de recherche translationnelle mené en collaboration entre différents partenaires européens, qui apporteront des ressources, notamment des données, issues de cohortes de patients. Ils développeront également des tests de diagnostic pour les auto-anticorps, qui serviront à prédire les effets indésirables de la COVID-19.

Objectif

"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."

Coordinateur

AARHUS UNIVERSITET
Contribution nette de l'UE
€ 1 138 996,25
Adresse
NORDRE RINGGADE 1
8000 Aarhus C
Danemark

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Région
Danmark Midtjylland Østjylland
Type d’activité
Higher or Secondary Education Establishments
Liens
Coût total
€ 1 138 996,25

Participants (18)

Partenaires (3)