Inborn errors of type I IFN immunity in patients with life-threatening COVID-19.
Adolescent
Adult
Aged
Aged, 80 and over
Alleles
Asymptomatic Infections
Betacoronavirus
COVID-19
Child
Child, Preschool
Coronavirus Infections
/ genetics
Female
Genetic Loci
Genetic Predisposition to Disease
Humans
Infant
Interferon Regulatory Factor-7
/ deficiency
Interferon Type I
/ immunology
Loss of Function Mutation
Male
Middle Aged
Pandemics
Pneumonia, Viral
/ genetics
Receptor, Interferon alpha-beta
/ deficiency
SARS-CoV-2
Toll-Like Receptor 3
/ deficiency
Young Adult
Journal
Science (New York, N.Y.)
ISSN: 1095-9203
Titre abrégé: Science
Pays: United States
ID NLM: 0404511
Informations de publication
Date de publication:
23 10 2020
23 10 2020
Historique:
received:
22
06
2020
accepted:
16
09
2020
pubmed:
26
9
2020
medline:
18
11
2020
entrez:
25
9
2020
Statut:
ppublish
Résumé
Clinical outcome upon infection with severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) ranges from silent infection to lethal coronavirus disease 2019 (COVID-19). We have found an enrichment in rare variants predicted to be loss-of-function (LOF) at the 13 human loci known to govern Toll-like receptor 3 (TLR3)- and interferon regulatory factor 7 (IRF7)-dependent type I interferon (IFN) immunity to influenza virus in 659 patients with life-threatening COVID-19 pneumonia relative to 534 subjects with asymptomatic or benign infection. By testing these and other rare variants at these 13 loci, we experimentally defined LOF variants underlying autosomal-recessive or autosomal-dominant deficiencies in 23 patients (3.5%) 17 to 77 years of age. We show that human fibroblasts with mutations affecting this circuit are vulnerable to SARS-CoV-2. Inborn errors of TLR3- and IRF7-dependent type I IFN immunity can underlie life-threatening COVID-19 pneumonia in patients with no prior severe infection.
Identifiants
pubmed: 32972995
pii: science.abd4570
doi: 10.1126/science.abd4570
pmc: PMC7857407
mid: NIHMS1668514
pii:
doi:
Substances chimiques
IFNAR1 protein, human
0
IRF7 protein, human
0
Interferon Regulatory Factor-7
0
Interferon Type I
0
TLR3 protein, human
0
Toll-Like Receptor 3
0
Receptor, Interferon alpha-beta
156986-95-7
Banques de données
Dryad
['10.5061/dryad.8pk0p2nkk']
Types de publication
Journal Article
Research Support, Non-U.S. Gov't
Langues
eng
Sous-ensembles de citation
IM
Subventions
Organisme : MRF
ID : MRF_C0483
Pays : United Kingdom
Organisme : NIAID NIH HHS
ID : HHSN272201400008C
Pays : United States
Organisme : NIAID NIH HHS
ID : R01 AI091707
Pays : United States
Organisme : NCATS NIH HHS
ID : UL1 TR001863
Pays : United States
Organisme : NCATS NIH HHS
ID : UL1 TR001866
Pays : United States
Organisme : NIAID NIH HHS
ID : P01 AI138938
Pays : United States
Organisme : NIAID NIH HHS
ID : HHSN272201800048C
Pays : United States
Organisme : NIAID NIH HHS
ID : R01 AI088364
Pays : United States
Organisme : Medical Research Council
ID : MR/S032304/1
Pays : United Kingdom
Organisme : NIAID NIH HHS
ID : U19 AI135972
Pays : United States
Organisme : NIAID NIH HHS
ID : U19 AI111825
Pays : United States
Organisme : NIAID NIH HHS
ID : 75N93019C00051
Pays : United States
Organisme : NCATS NIH HHS
ID : UL1 TR001873
Pays : United States
Organisme : NHGRI NIH HHS
ID : U24 HG008956
Pays : United States
Organisme : NHLBI NIH HHS
ID : R35 HL135834
Pays : United States
Organisme : NHGRI NIH HHS
ID : UM1 HG006504
Pays : United States
Organisme : NIAID NIH HHS
ID : U19 AI142733
Pays : United States
Investigateurs
Giuseppe Foti
(G)
Giacomo Bellani
(G)
Giuseppe Citerio
(G)
Ernesto Contro
(E)
Alberto Pesci
(A)
Maria Grazia Valsecchi
(MG)
Marina Cazzaniga
(M)
Jorge Abad
(J)
Sergio Aguilera-Albesa
(S)
Ozge Metin Akcan
(OM)
Ilad Alavi Darazam
(IA)
Juan C Aldave
(JC)
Miquel Alfonso Ramos
(MA)
Seyed Alireza Nadji
(SA)
Gulsum Alkan
(G)
Jerome Allardet-Servent
(J)
Luis M Allende
(LM)
Laia Alsina
(L)
Marie-Alexandra Alyanakian
(MA)
Blanca Amador-Borrero
(B)
Zahir Amoura
(Z)
Arnau Antolí
(A)
Sevket Arslan
(S)
Sophie Assant
(S)
Terese Auguet
(T)
Axelle Azot
(A)
Fanny Bajolle
(F)
Aurélie Baldolli
(A)
Maite Ballester
(M)
Hagit Baris Feldman
(HB)
Benoit Barrou
(B)
Alexandra Beurton
(A)
Agurtzane Bilbao
(A)
Geraldine Blanchard-Rohner
(G)
Ignacio Blanco
(I)
Adeline Blandinières
(A)
Daniel Blazquez-Gamero
(D)
Marketa Bloomfield
(M)
Mireia Bolivar-Prados
(M)
Raphael Borie
(R)
Cédric Bosteels
(C)
Ahmed A Bousfiha
(AA)
Claire Bouvattier
(C)
Oksana Boyarchuk
(O)
Maria Rita P Bueno
(MRP)
Jacinta Bustamante
(J)
Juan José Cáceres Agra
(JJ)
Semra Calimli
(S)
Ruggero Capra
(R)
Maria Carrabba
(M)
Carlos Casasnovas
(C)
Marion Caseris
(M)
Martin Castelle
(M)
Francesco Castelli
(F)
Martín Castillo de Vera
(MC)
Mateus V Castro
(MV)
Emilie Catherinot
(E)
Martin Chalumeau
(M)
Bruno Charbit
(B)
Matthew P Cheng
(MP)
Père Clavé
(P)
Bonaventura Clotet
(B)
Anna Codina
(A)
Fatih Colkesen
(F)
Fatma Çölkesen
(F)
Roger Colobran
(R)
Cloé Comarmond
(C)
David Dalmau
(D)
David Ross Darley
(DR)
Nicolas Dauby
(N)
Stéphane Dauger
(S)
Loic de Pontual
(L)
Amin Dehban
(A)
Geoffroy Delplancq
(G)
Alexandre Demoule
(A)
Jean-Luc Diehl
(JL)
Stephanie Dobbelaere
(S)
Sophie Durand
(S)
Waleed Eldars
(W)
Mohamed Elgamal
(M)
Marwa H Elnagdy
(MH)
Melike Emiroglu
(M)
Emine Hafize Erdeniz
(EH)
Selma Erol Aytekin
(SE)
Romain Euvrard
(R)
Recep Evcen
(R)
Giovanna Fabio
(G)
Laurence Faivre
(L)
Antonin Falck
(A)
Muriel Fartoukh
(M)
Morgane Faure
(M)
Miguel Fernandez Arquero
(MF)
Carlos Flores
(C)
Bruno Francois
(B)
Victoria Fumadó
(V)
Francesca Fusco
(F)
Blanca Garcia Solis
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Pascale Gaussem
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Juana Gil-Herrera
(J)
Laurent Gilardin
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Monica Girona Alarcon
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Timokratis Karamitros
(T)
Kai Kisand
(K)
Cheng-Lung Ku
(CL)
Yu-Lung Lau
(YL)
Yun Ling
(Y)
Carrie L Lucas
(CL)
Tom Maniatis
(T)
Davoud Mansouri
(D)
Laszlo Marodi
(L)
Isabelle Meyts
(I)
Joshua Milner
(J)
Kristina Mironska
(K)
Trine Mogensen
(T)
Tomohiro Morio
(T)
Lisa F P Ng
(LFP)
Luigi D Notarangelo
(LD)
Antonio Novelli
(A)
Giuseppe Novelli
(G)
Cliona O'Farrelly
(C)
Satoshi Okada
(S)
Tayfun Ozcelik
(T)
Rebeca Perez de Diego
(RP)
Anna M Planas
(AM)
Carolina Prando
(C)
Aurora Pujol
(A)
Lluis Quintana-Murci
(L)
Laurent Renia
(L)
Alessandra Renieri
(A)
Carlos Rodríguez-Gallego
(C)
Vanessa Sancho-Shimizu
(V)
Vijay Sankaran
(V)
Kelly Schiabor Barrett
(KS)
Mohammed Shahrooei
(M)
Andrew Snow
(A)
Pere Soler-Palacín
(P)
András N Spaan
(AN)
Stuart Tangye
(S)
Stuart Turvey
(S)
Furkan Uddin
(F)
Mohammed J Uddin
(MJ)
Diederik van de Beek
(D)
Sara E Vazquez
(SE)
Donald C Vinh
(DC)
Horst von Bernuth
(H)
Nicole Washington
(N)
Pawel Zawadzki
(P)
Helen C Su
(HC)
Jean-Laurent Casanova
(JL)
Huie Jing
(H)
Wesley Tung
(W)
Christopher R Luthers
(CR)
Bradly M Bauman
(BM)
Samantha Shafer
(S)
Lixin Zheng
(L)
Zinan Zhang
(Z)
Satoshi Kubo
(S)
Samuel D Chauvin
(SD)
Kazuyuki Meguro
(K)
Elana Shaw
(E)
Michael Lenardo
(M)
Justin Lack
(J)
Eric Karlins
(E)
Daniel M Hupalo
(DM)
John Rosenberger
(J)
Gauthaman Sukumar
(G)
Matthew D Wilkerson
(MD)
Xijun Zhang
(X)
Commentaires et corrections
Type : CommentIn
Type : CommentIn
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