Journal article
Humans with inherited MyD88 and IRAK-4 deficiencies are predisposed to hypoxemic COVID-19 pneumonia
The Journal of experimental medicine, Vol.220(5), e20220170
01 May 2023
PMID: 36880831
Featured in Collection : UN Sustainable Development Goals @ Drexel
Abstract
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.
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Details
- Title
- Humans with inherited MyD88 and IRAK-4 deficiencies are predisposed to hypoxemic COVID-19 pneumonia
- Creators
- Ana García-García - Clinical Immunology Unit, Hospital Sant Joan de Déu-Hospital Clínic Barcelona , Barcelona, SpainRebeca Pérez de Diego - Hospital La Paz Institute for Health ResearchCarlos Flores - Instituto Tecnológico y de Energías RenovablesDarawan Rinchai - Rockefeller UniversityJordi Solé-Violán - Dept. of Intensive Care Medicine, University Hospital of Gran Canaria Dr. Negrin, Canarian Health System , Las Palmas de Gran Canaria, SpainÀngela Deyà-Martínez - Clinical Immunology Unit, Hospital Sant Joan de Déu-Hospital Clínic Barcelona , Barcelona, SpainBlanca García-Solis - Laboratory of Immunogenetics of Human Diseases, IdiPAZ Institute for Health Research, La Paz Hospital , Madrid, SpainJosé M Lorenzo-Salazar - Instituto Tecnológico y de Energías RenovablesElisa Hernández-Brito - Hospital Universitario de Gran Canaria Doctor NegrínAnna-Lisa Lanz - Ludwig-Maximilians-Universität MünchenLeen Moens - KU LeuvenGiorgia Bucciol - KU LeuvenMohamed Almuqamam - St. Christopher's Hospital for ChildrenJoseph B Domachowske - SUNY Upstate Medical UniversityElena Colino - Hospital Universitario Insular de Gran CanariaJuan Luis Santos-Perez - Unidad de Gestión Clínica de Pediatría y Cirugía Pediátrica, Hospital Virgen de las Nieves-IBS , Granada, SpainFrancisco M Marco - Alicante Institute for Health and Biomedical Research , Alicante, SpainClaudio Pignata - Federico II University HospitalAziz Bousfiha - Clinical Immunology, Autoimmunity and Inflammation Laboratory, Faculty of Medicine and Pharmacy, Hassan II University , Casablanca, MoroccoStefanie Bauer - Clinic for Children and Adolescents. Dept. of Hematology and Oncology. University Clinic Erlangen , Erlangen, GermanyStuart E Turvey - British Columbia Children's HospitalFilomeen Haerynck - Ghent University HospitalJavier Gonzalo Ocejo-Vinyals - Marqués de Valdecilla University HospitalFrancisco Lendinez - Dept. of Pediatric Oncohematology, Hospital Materno Infantil Torrecárdenas , Almería, SpainSeraina Prader - University Children's Hospital ZurichNora Naumann-Bartsch - Clinic for Children and Adolescents. Dept. of Hematology and Oncology. University Clinic Erlangen , Erlangen, GermanyJana Pachlopnik SchmidCatherine M Biggs - British Columbia Children's HospitalKyla Hildebrand - British Columbia Children's HospitalAlexandra Dreesman - Centre Hospitalier Universitaire de Saint-PierreMiguel Ángel Cárdenes - Hospital Universitario de Gran Canaria Doctor NegrínFatima Ailal - University of Hassan II CasablancaIbtihal Benhsaien - University of Hassan II CasablancaGiuliana Giardino - Federico II University HospitalAgueda Molina-Fuentes - Dept. of Immunology, UGC Laboratories, University Hospital of Jaén , Jaén, SpainClaudia Fortuny - Universitat de BarcelonaSwetha Madhavarapu - Drexel University, PediatricsDaniel H Conway - Drexel University, PediatricsCarolina Prando - Instituto de Pesquisa Pelé Pequeno Príncipe, Faculdades Pequeno Príncipe, Hospital Pequeno Príncipe , Curitiba, BrazilLaire Schidlowski - Instituto de Pesquisa Pelé Pequeno Príncipe, Faculdades Pequeno Príncipe, Hospital Pequeno Príncipe , Curitiba, BrazilMaría Teresa Martínez de Saavedra Álvarez - Dept. of Immunology, University Hospital of Gran Canaria Dr. Negrin, Canarian Health System , Las Palmas de Gran Canaria, SpainRafael Alfaro - Hospital Universitario de Gran Canaria Doctor NegrínFelipe Rodríguez de Castro - Universidad de Las Palmas de Gran CanariaIsabelle Meyts - KU LeuvenFabian Hauck - Ludwig-Maximilians-Universität MünchenAnne Puel - Rockefeller UniversityPaul Bastard - Assistance Publique – Hôpitaux de ParisBertrand Boisson - Rockefeller UniversityEmmanuelle Jouanguy - Rockefeller UniversityLaurent Abel - Rockefeller UniversityAurélie Cobat - InsermQian Zhang - Rockefeller UniversityJean-Laurent Casanova - Howard Hughes Medical Institute , New York, NY, USALaia Alsina - Hospital Sant Joan de Déu BarcelonaCarlos Rodríguez-Gallego - Universidad Fernando Pessoa CanariasESID Registry Working Party
- Publication Details
- The Journal of experimental medicine, Vol.220(5), e20220170
- Grant note
- MR/S032304/1 / Medical Research Council R01 AI088364 / NIAID NIH HHS UL1 RR024143 / NCRR NIH HHS R01 AI163029 / NIAID NIH HHS UL1 TR001866 / NCATS NIH HHS Howard Hughes Medical Institute
- Resource Type
- Journal article
- Language
- English
- Academic Unit
- Pediatrics
- Web of Science ID
- WOS:000951708800001
- Scopus ID
- 2-s2.0-85162241800
- Other Identifier
- 991021448154404721
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- Domestic collaboration
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- Web of Science research areas
- Immunology
- Medicine, Research & Experimental