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

Projektbeschreibung

Die Determinanten der Manifestation einer SARS-CoV-2-Exposition

Die klinischen Manifestationen der SARS-CoV-2-Exposition weisen eine große Variabilität auf, die teilweise durch Komorbiditäten erklärt werden kann. Jüngste Erkenntnisse deuten darauf hin, dass angeborene Fehler der Immunität oder das Vorhandensein von Autoantikörpern mit COVID-19-bedingter Lungenentzündung in Verbindung stehen. Das EU-finanzierte Projekt UNDINE zielt darauf ab, weitere Nachweise für diese Annahme zu finden. Zudem soll es Informationen über die genetischen und immunologischen Grundlagen von Variationen der klinischen Manifestationen nach SARS-CoV-2-Exposition liefern. Bei dem Projekt handelt es sich um eine gemeinsame translationale Forschungsarbeit verschiedener europäischer Partner, die Ressourcen, einschließlich Daten von Patientenkohorten, beisteuern werden. Darüber hinaus werden diagnostische Tests für Autoantikörper entwickelt, mit denen sich unerwünschte Wirkungen von COVID-19 vorhersagen lassen.

Ziel

"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."

Koordinator

AARHUS UNIVERSITET
Netto-EU-Beitrag
€ 1 138 996,25
Adresse
NORDRE RINGGADE 1
8000 Aarhus C
Dänemark

Auf der Karte ansehen

Region
Danmark Midtjylland Østjylland
Aktivitätstyp
Higher or Secondary Education Establishments
Links
Gesamtkosten
€ 1 138 996,25

Beteiligte (18)

Partner (3)