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

Descripción del proyecto

Los determinantes de la manifestación de la exposición al SARS-CoV-2

Las manifestaciones clínicas de la exposición al coronavirus del síndrome respiratorio agudo grave 2 (SARS-CoV-2) presentan una gran variabilidad, lo cual puede explicarse en parte por las comorbilidades. Pruebas recientes indican que errores innatos de inmunidad o la presencia de autoanticuerpos están asociados a la neumonía por COVID-19. El proyecto UNDINE, financiado con fondos europeos, pretende ampliar estas pruebas y proporcionar información sobre la base genética e inmunológica de las variaciones en las manifestaciones clínicas tras la exposición al SARS-CoV-2. El proyecto es un esfuerzo de investigación traslacional y colaborativo entre diferentes socios europeos, que aportarán recursos, incluidos datos, de cohortes de pacientes. Además, desarrollarán unas pruebas de diagnóstico para autoanticuerpos como medio para predecir los efectos adversos de la COVID-19.

Objetivo

"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."

Coordinador

AARHUS UNIVERSITET
Aportación neta de la UEn
€ 1 138 996,25
Dirección
NORDRE RINGGADE 1
8000 Aarhus C
Dinamarca

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Región
Danmark Midtjylland Østjylland
Tipo de actividad
Higher or Secondary Education Establishments
Enlaces
Coste total
€ 1 138 996,25

Participantes (18)

Socios (3)