Humans with inherited MyD88 and IRAK-4 deficiencies are predisposed to hypoxemic COVID-19 pneumonia

© 2023 García García et al..

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.

Errataetall:

CommentIn: Transplantation. 2023 Oct 1;107(10):2084-2086. - PMID 37749810

Medienart:

E-Artikel

Erscheinungsjahr:

2023

Erschienen:

2023

Enthalten in:

Zur Gesamtaufnahme - volume:220

Enthalten in:

The Journal of experimental medicine - 220(2023), 5 vom: 01. Mai

Sprache:

Englisch

Beteiligte Personen:

García-García, Ana [VerfasserIn]
Pérez de Diego, Rebeca [VerfasserIn]
Flores, Carlos [VerfasserIn]
Rinchai, Darawan [VerfasserIn]
Solé-Violán, Jordi [VerfasserIn]
Deyà-Martínez, Àngela [VerfasserIn]
García-Solis, Blanca [VerfasserIn]
Lorenzo-Salazar, José M [VerfasserIn]
Hernández-Brito, Elisa [VerfasserIn]
Lanz, Anna-Lisa [VerfasserIn]
Moens, Leen [VerfasserIn]
Bucciol, Giorgia [VerfasserIn]
Almuqamam, Mohamed [VerfasserIn]
Domachowske, Joseph B [VerfasserIn]
Colino, Elena [VerfasserIn]
Santos-Perez, Juan Luis [VerfasserIn]
Marco, Francisco M [VerfasserIn]
Pignata, Claudio [VerfasserIn]
Bousfiha, Aziz [VerfasserIn]
Turvey, Stuart E [VerfasserIn]
Bauer, Stefanie [VerfasserIn]
Haerynck, Filomeen [VerfasserIn]
Ocejo-Vinyals, Javier Gonzalo [VerfasserIn]
Lendinez, Francisco [VerfasserIn]
Prader, Seraina [VerfasserIn]
Naumann-Bartsch, Nora [VerfasserIn]
Pachlopnik Schmid, Jana [VerfasserIn]
Biggs, Catherine M [VerfasserIn]
Hildebrand, Kyla [VerfasserIn]
Dreesman, Alexandra [VerfasserIn]
Cárdenes, Miguel Ángel [VerfasserIn]
Ailal, Fatima [VerfasserIn]
Benhsaien, Ibtihal [VerfasserIn]
Giardino, Giuliana [VerfasserIn]
Molina-Fuentes, Agueda [VerfasserIn]
Fortuny, Claudia [VerfasserIn]
Madhavarapu, Swetha [VerfasserIn]
Conway, Daniel H [VerfasserIn]
Prando, Carolina [VerfasserIn]
Schidlowski, Laire [VerfasserIn]
Martínez de Saavedra Álvarez, María Teresa [VerfasserIn]
Alfaro, Rafael [VerfasserIn]
Rodríguez de Castro, Felipe [VerfasserIn]
ESID Registry Working Party [VerfasserIn]
COVID Human Genetic Effort [VerfasserIn]
Meyts, Isabelle [VerfasserIn]
Hauck, Fabian [VerfasserIn]
Puel, Anne [VerfasserIn]
Bastard, Paul [VerfasserIn]
Boisson, Bertrand [VerfasserIn]
Jouanguy, Emmanuelle [VerfasserIn]
Abel, Laurent [VerfasserIn]
Cobat, Aurélie [VerfasserIn]
Zhang, Qian [VerfasserIn]
Casanova, Jean-Laurent [VerfasserIn]
Alsina, Laia [VerfasserIn]
Rodríguez-Gallego, Carlos [VerfasserIn]
Kindle, Gerhard [Sonstige Person]
Mahlaoui, Nizar [Sonstige Person]
Seidel, Markus G [Sonstige Person]
Vassilios, Lougaris [Sonstige Person]
Seppänen, Mikko R J [Sonstige Person]
Abel, Laurent [Sonstige Person]
Aiuti, Alessandro [Sonstige Person]
Al-Muhsen, Saleh [Sonstige Person]
Al-Mulla, Fahd [Sonstige Person]
Anderson, Mark S [Sonstige Person]
Andreakos, Evangelos [Sonstige Person]
Arias, Andrés A [Sonstige Person]
Baris Feldman, Hagit [Sonstige Person]
Belot, Alexandre [Sonstige Person]
Biggs, Catherine M [Sonstige Person]
Bogunovic, Dusan [Sonstige Person]
Bolze, Alexandre [Sonstige Person]
Bondarenko, Anastasiia [Sonstige Person]
Bousfiha, Ahmed A [Sonstige Person]
Brodin, Petter [Sonstige Person]
Bryceson, Yenan [Sonstige Person]
Bustamante, Carlos D [Sonstige Person]
Butte, Manish J [Sonstige Person]
Casari, Giorgio [Sonstige Person]
Christodoulou, John [Sonstige Person]
Condino-Neto, Antonio [Sonstige Person]
Constantinescu, Stefan N [Sonstige Person]
Cooper, Megan A [Sonstige Person]
Dalgard, Clifton L [Sonstige Person]
Desai, Murkesh [Sonstige Person]
Drolet, Beth A [Sonstige Person]
El Baghdadi, Jamila [Sonstige Person]
Espinosa-Padilla, Sara [Sonstige Person]
Fellay, Jacques [Sonstige Person]
Flores, Carlos [Sonstige Person]
Franco, José Luis [Sonstige Person]
Froidure, Antoine [Sonstige Person]
Gregersen, Peter K [Sonstige Person]
Grimbacher, Bodo [Sonstige Person]
Haerynck, Filomeen [Sonstige Person]
Hagin, David [Sonstige Person]
Halwani, Rabih [Sonstige Person]
Hammarström, Lennart [Sonstige Person]
Heath, James R [Sonstige Person]
Henrickson, Sarah E [Sonstige Person]
Hsieh, Elena W Y [Sonstige Person]
Husebye, Eystein [Sonstige Person]
Imai, Kohsuke [Sonstige Person]
Itan, Yuval [Sonstige Person]
Jarvis, Erich D [Sonstige Person]
Karamitros, Timokratis [Sonstige Person]
Kisand, Kai [Sonstige Person]
Ku, Cheng-Lung [Sonstige Person]
Lau, Yu-Lung [Sonstige Person]
Ling, Yun [Sonstige Person]
Lucas, Carrie L [Sonstige Person]
Maniatis, Tom [Sonstige Person]
Mansouri, Davood [Sonstige Person]
Maródi, László [Sonstige Person]
Meyts, Isabelle [Sonstige Person]
Milner, Joshua D [Sonstige Person]
Mironska, Kristina [Sonstige Person]
Mogensen, Trine H [Sonstige Person]
Morio, Tomohiro [Sonstige Person]
Ng, Lisa F P [Sonstige Person]
Notarangelo, Luigi D [Sonstige Person]
Novelli, Antonio [Sonstige Person]
Novelli, Giuseppe [Sonstige Person]
O'Farrelly, Cliona [Sonstige Person]
Okada, Satoshi [Sonstige Person]
Okamoto, Keisuke [Sonstige Person]
Ozcelik, Tayfun [Sonstige Person]
Pan-Hammarström, Qiang [Sonstige Person]
Pape, Jean W [Sonstige Person]
Perez de Diego, Rebecca [Sonstige Person]
Perlin, David S [Sonstige Person]
Pesole, Graziano [Sonstige Person]
Planas, Anna M [Sonstige Person]
Prando, Carolina [Sonstige Person]
Pujol, Aurora [Sonstige Person]
Quintana-Murci, Lluis [Sonstige Person]
Ramaswamy, Sathishkumar [Sonstige Person]
Renia, Laurent [Sonstige Person]
Resnick, Igor [Sonstige Person]
Rodríguez-Gallego, Carlos [Sonstige Person]
Sancho-Shimizu, Vanessa [Sonstige Person]
Sediva, Anna [Sonstige Person]
Seppänan, Mikko R J [Sonstige Person]
Shahrooei, Mohammed [Sonstige Person]
Shcherbina, Anna [Sonstige Person]
Slaby, Ondrej [Sonstige Person]
Snow, Andrew L [Sonstige Person]
Soler-Palacín, Pere [Sonstige Person]
Spaan, András N [Sonstige Person]
Tancevski, Ivan [Sonstige Person]
Tangye, Stuart G [Sonstige Person]
Tayoun, Ahmad Abou [Sonstige Person]
Turvey, Stuart E [Sonstige Person]
Uddin, K M Furkan [Sonstige Person]
Uddin, Mohammed J [Sonstige Person]

Links:

Volltext

Themen:

Adaptor Proteins, Signal Transducing
EC 2.7.11.1
IRAK4 protein, human
Journal Article
MYD88 protein, human
Myeloid Differentiation Factor 88
Research Support, N.I.H., Intramural
Research Support, Non-U.S. Gov't
Toll-Like Receptor 7

Anmerkungen:

Date Completed 14.03.2023

Date Revised 30.03.2024

published: Print-Electronic

CommentIn: Transplantation. 2023 Oct 1;107(10):2084-2086. - PMID 37749810

Citation Status MEDLINE

doi:

10.1084/jem.20220170

funding:

Förderinstitution / Projekttitel:

PPN (Katalog-ID):

NLM353866318