Humans with inherited MyD88 and IRAK-4 deficiencies are predisposed to hypoxemic COVID-19 pneumonia.
Journal
The Journal of experimental medicine
ISSN: 1540-9538
Titre abrégé: J Exp Med
Pays: United States
ID NLM: 2985109R
Informations de publication
Date de publication:
01 05 2023
01 05 2023
Historique:
received:
28
01
2022
revised:
11
11
2022
accepted:
30
01
2023
entrez:
7
3
2023
pubmed:
8
3
2023
medline:
10
3
2023
Statut:
ppublish
Résumé
X-linked recessive deficiency of TLR7, a MyD88- and IRAK-4-dependent endosomal ssRNA sensor, impairs SARS-CoV-2 recognition and type I IFN production in plasmacytoid dendritic cells (pDCs), thereby underlying hypoxemic COVID-19 pneumonia with high penetrance. We report 22 unvaccinated patients with autosomal recessive MyD88 or IRAK-4 deficiency infected with SARS-CoV-2 (mean age: 10.9 yr; 2 mo to 24 yr), originating from 17 kindreds from eight countries on three continents. 16 patients were hospitalized: six with moderate, four with severe, and six with critical pneumonia, one of whom died. The risk of hypoxemic pneumonia increased with age. The risk of invasive mechanical ventilation was also much greater than in age-matched controls from the general population (OR: 74.7, 95% CI: 26.8-207.8, P < 0.001). The patients' susceptibility to SARS-CoV-2 can be attributed to impaired TLR7-dependent type I IFN production by pDCs, which do not sense SARS-CoV-2 correctly. Patients with inherited MyD88 or IRAK-4 deficiency were long thought to be selectively vulnerable to pyogenic bacteria, but also have a high risk of hypoxemic COVID-19 pneumonia.
Identifiants
pubmed: 36880831
pii: 213920
doi: 10.1084/jem.20220170
pmc: PMC9998661
pii:
doi:
Substances chimiques
Adaptor Proteins, Signal Transducing
0
Myeloid Differentiation Factor 88
0
Toll-Like Receptor 7
0
IRAK4 protein, human
EC 2.7.11.1
MYD88 protein, human
0
Types de publication
Journal Article
Research Support, Non-U.S. Gov't
Research Support, N.I.H., Intramural
Langues
eng
Sous-ensembles de citation
IM
Subventions
Organisme : Howard Hughes Medical Institute
Pays : United States
Organisme : NCRR NIH HHS
ID : UL1 RR024143
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 : R01 AI163029
Pays : United States
Investigateurs
Gerhard Kindle
(G)
Nizar Mahlaoui
(N)
Markus G Seidel
(MG)
Lougaris Vassilios
(L)
Mikko R J Seppänen
(MRJ)
Laurent Abel
(L)
Alessandro Aiuti
(A)
Saleh Al-Muhsen
(S)
Fahd Al-Mulla
(F)
Mark S Anderson
(MS)
Evangelos Andreakos
(E)
Andrés A Arias
(AA)
Hagit Baris Feldman
(H)
Alexandre Belot
(A)
Catherine M Biggs
(CM)
Dusan Bogunovic
(D)
Alexandre Bolze
(A)
Anastasiia Bondarenko
(A)
Ahmed A Bousfiha
(AA)
Petter Brodin
(P)
Yenan Bryceson
(Y)
Carlos D Bustamante
(CD)
Manish J Butte
(MJ)
Giorgio Casari
(G)
John Christodoulou
(J)
Antonio Condino-Neto
(A)
Stefan N Constantinescu
(SN)
Megan A Cooper
(MA)
Clifton L Dalgard
(CL)
Murkesh Desai
(M)
Beth A Drolet
(BA)
Jamila El Baghdadi
(J)
Sara Espinosa-Padilla
(S)
Jacques Fellay
(J)
Carlos Flores
(C)
José Luis Franco
(JL)
Antoine Froidure
(A)
Peter K Gregersen
(PK)
Bodo Grimbacher
(B)
Filomeen Haerynck
(F)
David Hagin
(D)
Rabih Halwani
(R)
Lennart Hammarström
(L)
James R Heath
(JR)
Sarah E Henrickson
(SE)
Elena W Y Hsieh
(EWY)
Eystein Husebye
(E)
Kohsuke Imai
(K)
Yuval Itan
(Y)
Erich D Jarvis
(ED)
Timokratis Karamitros
(T)
Kai Kisand
(K)
Cheng-Lung Ku
(CL)
Yu-Lung Lau
(YL)
Yun Ling
(Y)
Carrie L Lucas
(CL)
Tom Maniatis
(T)
Davood Mansouri
(D)
László Maródi
(L)
Isabelle Meyts
(I)
Joshua D Milner
(JD)
Kristina Mironska
(K)
Trine H Mogensen
(TH)
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)
Keisuke Okamoto
(K)
Tayfun Ozcelik
(T)
Qiang Pan-Hammarström
(Q)
Jean W Pape
(JW)
Rebecca Perez de Diego
(R)
David S Perlin
(DS)
Graziano Pesole
(G)
Anna M Planas
(AM)
Carolina Prando
(C)
Aurora Pujol
(A)
Lluis Quintana-Murci
(L)
Sathishkumar Ramaswamy
(S)
Laurent Renia
(L)
Igor Resnick
(I)
Carlos Rodríguez-Gallego
(C)
Vanessa Sancho-Shimizu
(V)
Anna Sediva
(A)
Mikko R J Seppänan
(MRJ)
Mohammed Shahrooei
(M)
Anna Shcherbina
(A)
Ondrej Slaby
(O)
Andrew L Snow
(AL)
Pere Soler-Palacín
(P)
András N Spaan
(AN)
Ivan Tancevski
(I)
Stuart G Tangye
(SG)
Ahmad Abou Tayoun
(AA)
Stuart E Turvey
(SE)
K M Furkan Uddin
(KMF)
Mohammed J Uddin
(MJ)
Diederik van de Beek
(D)
Donald C Vinh
(DC)
Horst von Bernuth
(H)
Joost Wauters
(J)
Mayana Zatz
(M)
Pawel Zawadzki
(P)
Helen C Su
(HC)
Jean-Laurent Casanova
(JL)
Commentaires et corrections
Type : CommentIn
Informations de copyright
© 2023 García García et al.
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