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

Descrizione del progetto

I determinanti della manifestazione dell’esposizione alla SARS-CoV-2

Le manifestazioni cliniche dell’esposizione alla SARS-CoV-2 presentano una grande variabilità, che può essere in parte spiegata dalle comorbidità. Dati recenti indicano che gli errori innati dell’immunità o la presenza di autoanticorpi sono associati alla polmonite da COVID-19. Il progetto UNDINE, finanziato dall’UE, si propone di ampliare tali dati e di fornire informazioni sulle basi genetiche e immunologiche delle variazioni nelle manifestazioni cliniche in seguito all’esposizione alla SARS-CoV-2. Il progetto costituisce uno sforzo di ricerca traslazionale collaborativa tra diversi partner europei, che contribuiranno con risorse, compresi i dati, delle coorti di pazienti. Verranno inoltre sviluppati test diagnostici per gli autoanticorpi come mezzo per prevedere gli effetti avversi della COVID-19.

Obiettivo

"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."

Coordinatore

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

Mostra sulla mappa

Regione
Danmark Midtjylland Østjylland
Tipo di attività
Higher or Secondary Education Establishments
Collegamenti
Costo totale
€ 1 138 996,25

Partecipanti (18)

Partner (3)