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

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."

Coordinator

AARHUS UNIVERSITET
Net EU contribution
€ 1 138 996,25
Address
Nordre Ringgade 1
8000 Aarhus C
Denmark

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Region
Danmark Midtjylland Østjylland
Activity type
Higher or Secondary Education Establishments
Non-EU contribution
€ 0,00

Participants (18)

INSTITUT NATIONAL DE LA SANTE ET DE LA RECHERCHE MEDICALE
France
Net EU contribution
€ 1 944 550,00
Address
Rue De Tolbiac 101
75654 Paris

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Region
Ile-de-France Ile-de-France Paris
Activity type
Research Organisations
Non-EU contribution
€ 0,00
INSTITUT PASTEUR
France
Net EU contribution
€ 443 380,00
Address
Rue Du Docteur Roux 25-28
75724 Paris Cedex 15

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Region
Ile-de-France Ile-de-France Paris
Activity type
Research Organisations
Non-EU contribution
€ 0,00
KATHOLIEKE UNIVERSITEIT LEUVEN
Belgium
Net EU contribution
€ 312 500,00
Address
Oude Markt 13
3000 Leuven

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Region
Vlaams Gewest Prov. Vlaams-Brabant Arr. Leuven
Activity type
Higher or Secondary Education Establishments
Non-EU contribution
€ 0,00
UNIVERSITA DEGLI STUDI DI ROMA TOR VERGATA
Italy
Net EU contribution
€ 125 000,00
Address
Via Cracovia 50
00133 Roma

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Region
Centro (IT) Lazio Roma
Activity type
Higher or Secondary Education Establishments
Non-EU contribution
€ 0,00
OSPEDALE SAN RAFFAELE SRL
Italy
Net EU contribution
€ 299 998,75
Address
Via Olgettina 60
20132 Milano

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Region
Nord-Ovest Lombardia Milano
Activity type
Private for-profit entities (excluding Higher or Secondary Education Establishments)
Non-EU contribution
€ 0,00
INSTITUT CATALA DE LA SALUT
Spain
Net EU contribution
€ 0,00
Address
Gran Via De Les Corts Catalanes 587
08007 Barcelona

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Region
Este Cataluña Barcelona
Activity type
Public bodies (excluding Research Organisations and Secondary or Higher Education Establishments)
Non-EU contribution
€ 0,00
Third-party

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.

FUNDACIO HOSPITAL UNIVERSITARI VALL D'HEBRON - INSTITUT DE RECERCA
Spain
Net EU contribution
€ 163 667,50
Address
Passeig Vall D Hebron 119-129 Edificio De Recerca
08035 Barcelona

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Region
Este Cataluña Barcelona
Activity type
Research Organisations
Non-EU contribution
€ 0,00
Third-party

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.

FUNDACIO INSTITUT D'INVESTIGACIO BIOMEDICA DE BELLVITGE
Spain
Net EU contribution
€ 77 353,75
Address
Avenida Gran Via Hospitalet 199-203
08908 L'hospitalet De Llobregat

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Region
Este Cataluña Barcelona
Activity type
Research Organisations
Non-EU contribution
€ 0,00
Third-party

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.

INSTITUT DE INVESTIGACIO EN CIENCIES DE LA SALUT GERMANS TRIAS I PUJOL
Spain
Net EU contribution
€ 71 502,50
Address
Ctra De Canyet S/n
08916 Badalona Barcelona

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Region
Este Cataluña Barcelona
Activity type
Research Organisations
Non-EU contribution
€ 0,00
UNIVERSITAIR MEDISCH CENTRUM UTRECHT
Netherlands
Net EU contribution
€ 312 193,75
Address
Heidelberglaan 100
3584 CX Utrecht

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Region
West-Nederland Utrecht Utrecht
Activity type
Higher or Secondary Education Establishments
Non-EU contribution
€ 0,00
TARTU ULIKOOL
Estonia
Net EU contribution
€ 121 062,50
Address
Ulikooli 18
51005 Tartu

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Region
Eesti Eesti Lõuna-Eesti
Activity type
Higher or Secondary Education Establishments
Non-EU contribution
€ 0,00
KAROLINSKA INSTITUTET
Sweden
Net EU contribution
€ 303 748,75
Address
Nobels Vag 5
17177 Stockholm

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Region
Östra Sverige Stockholm Stockholms län
Activity type
Higher or Secondary Education Establishments
Non-EU contribution
€ 0,00
DEUTSCHES PRIMATENZENTRUM GMBH
Germany
Net EU contribution
€ 350 000,00
Address
Kellnerweg 4
37077 Gottingen

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Region
Niedersachsen Braunschweig Göttingen
Activity type
Research Organisations
Non-EU contribution
€ 0,00
SERVICIO MADRILENO DE SALUD
Spain
Net EU contribution
€ 125 312,50
Address
Plaza Carlos Trias Bertran 7
28020 Madrid

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Region
Comunidad de Madrid Comunidad de Madrid Madrid
Activity type
Public bodies (excluding Research Organisations and Secondary or Higher Education Establishments)
Non-EU contribution
€ 0,00
BIOMERIEUX SA
France
Net EU contribution
€ 245 587,50
Address
Chemin De L'orme
69280 Marcy L'etoile

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Region
Auvergne-Rhône-Alpes Rhône-Alpes Rhône
Activity type
Private for-profit entities (excluding Higher or Secondary Education Establishments)
Non-EU contribution
€ 0,00
IDRYMA IATROVIOLOGIKON EREUNON AKADEMIAS ATHINON
Greece
Net EU contribution
€ 312 500,00
Address
Soranou Efesiou 4
115 27 Athina

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Region
Κεντρικός Τομέας Αθηνών Aττική Αττική
Activity type
Research Organisations
Non-EU contribution
€ 0,00
THE PROVOST, FELLOWS, FOUNDATION SCHOLARS & THE OTHER MEMBERS OF BOARD, OF THE COLLEGE OF THE HOLY & UNDIVIDED TRINITY OF QUEEN ELIZABETH NEAR DUBLIN
Ireland
Net EU contribution
€ 308 285,00
Address
College Green Trinity College
D02 CX56 Dublin 2

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Region
Ireland Eastern and Midland Dublin
Activity type
Higher or Secondary Education Establishments
Non-EU contribution
€ 0,00
AARHUS UNIVERSITETSHOSPITAL
Denmark
Net EU contribution
€ 62 500,00
Address
Palle Juul-jensens Boulevard 99
8200 Aarhus

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Region
Danmark Midtjylland Østjylland
Activity type
Research Organisations
Non-EU contribution
€ 0,00