Recessive inborn errors of type I IFN immunity in children with COVID-19 pneumonia-Reference-Cited by-同舟云学术

Recessive inborn errors of type I IFN immunity in children with COVID-19 pneumonia

Published:2022-06-16 Issue:8 Volume:219 Page:
ISSN:0022-1007
Container-title:Journal of Experimental Medicine
language:en
Short-container-title:

Author:

Zhang Qian¹²³^ORCID,Matuozzo Daniela²³^ORCID,Le Pen Jérémie⁴^ORCID,Lee Danyel¹²³^ORCID,Moens Leen⁴^ORCID,Asano Takaki¹^ORCID,Bohlen Jonathan²³^ORCID,Liu Zhiyong¹^ORCID,Moncada-Velez Marcela¹^ORCID,Kendir-Demirkol Yasemin¹^ORCID,Jing Huie⁵^ORCID,Bizien Lucy²³^ORCID,Marchal Astrid²³^ORCID,Abolhassani Hassan⁶⁷^ORCID,Delafontaine Selket⁸⁹^ORCID,Bucciol Giorgia⁸^ORCID,Abel Laurent,Abolhassani Hassan,Aiuti Alessandro,Akcan Ozge Metin,Al-Muhsen Saleh,Al-Mulla Fahd,Alkan Gulsum,Anderson Mark S.,Andreakos Evangelos,Arias Andrés A.,El Bakkouri Jalila,Baris Feldman Hagit,Belot Alexandre,Biggs Catherine M.,Bogunovic Dusan,Bolze Alexandre,Bondarenko Anastasiia,Bousfiha Ahmed A.,Bozdemir Sefika Elmas,Brodin Petter,Bryceson Yenan,Bustamante Carlos D.,Butte Manish J.,Casari Giorgio,Christodoulou John,Colobran Roger,Condino-Neto Antonio,Constantinescu Stefan N.,Cooper Megan A.,Dalgard Clifton L.,Desai Murkesh,Drolet Beth A.,El Baghdadi Jamila,Emiroglu Melike,Erdeniz Emine Hafize,Espinosa-Padilla Sara,Fellay Jacques,Flores Carlos,Franco José Luis,Froidure Antoine,Gregersen Peter K.,Grimbacher Bodo,Gulhan Belgin,Haerynck Filomeen,Hagin David,Halwani Rabih,Hammarström Lennart,Heath James R.,Henrickson Sarah E.,Hsieh Elena W.Y.,Husebye Eystein,Imai Kohsuke,Itan Yuval,Jabandziev Petr,Jarvis Erich D.,Karamitros Timokratis,Karbuz Adem,Kisand Kai,Ku Cheng-Lung,Lau Yu-Lung,Ling Yun,Lucas Carrie L.,Maniatis Tom,Mansouri Davood,Maródi László,Metin Ayse,Meyts Isabelle,Milner Joshua D.,Mironska Kristina,Mogensen Trine H.,Morio Tomohiro,Ng Lisa F.P.,Notarangelo Luigi D.,Novelli Antonio,Novelli Giuseppe,O'Farrelly Cliona,Okada Satoshi,Okamoto Keisuke,Tüter Öz Şadiye Kübra,Ozcelik Tayfun,Pan-Hammarström Qiang,Papadaki Maria,Pape Jean W.,Parlakay Aslinur Ozkaya,Perez de Diego Rebeca,Perlin David S.,Pesole Graziano,Planas Anna M.,Pokorna Petra,Prando Carolina,Pujol Aurora,Quintana-Murci Lluis,Ramaswamy Sathishkumar,Renia Laurent,Resnick Igor,Rivière Jacques G.,Rodríguez-Gallego Carlos,Sancho-Shimizu Vanessa,Sediva Anna,Seppänen Mikko R.J.,Shahrooei Mohammed,Shcherbina Anna,Slaba Katerina,Slaby Ondrej,Snow Andrew L.,Soler-Palacín Pere,De Somer Lien,Spaan András N.,Tancevski Ivan,Tangye Stuart G.,Abou Tayoun Ahmad,Thanos Dimitris,Turvey Stuart E.,Uddin K M Furkan,Uddin Mohammed J.,van de Beek Diederik,Vermeulen François,Vinh Donald C.,von Bernuth Horst,Wauters Joost,Wouters Carine,Yahsi Aysun,Kanik Yuksek Saliha,Zatz Mayana,Zawadzki Pawel,Su Helen C.,Casanova Jean-Laurent,Bayhan Gulsum Ical¹⁰^ORCID,Keles Sevgi¹¹^ORCID,Kiykim Ayca¹²^ORCID,Hancerli Selda¹³^ORCID,Haerynck Filomeen¹⁴^ORCID,Florkin Benoit¹⁵^ORCID,Hatipoglu Nevin¹⁶^ORCID,Ozcelik Tayfun¹⁷^ORCID,Morelle Guillaume¹⁸^ORCID,Zatz Mayana¹⁹^ORCID,Ng Lisa F.P.²⁰^ORCID,Lye David Chien²¹²²²³²⁴^ORCID,Young Barnaby Edward²¹²³²⁴^ORCID,Leo Yee-Sin²¹²²²³²⁴^ORCID,Dalgard Clifton L.²⁵²⁶^ORCID,Lifton Richard P.²⁷²⁸²⁹^ORCID,Renia Laurent²⁰²³³⁰^ORCID,Meyts Isabelle⁸^ORCID,Jouanguy Emmanuelle¹²³^ORCID,Hammarström Lennart⁶^ORCID,Pan-Hammarström Qiang⁶^ORCID,Boisson Bertrand¹²³^ORCID,Bastard Paul¹²³³¹^ORCID,Su Helen C.⁵^ORCID,Boisson-Dupuis Stéphanie¹²³^ORCID,Abel Laurent¹²³^ORCID,Rice Charles M.⁴^ORCID,Zhang Shen-Ying¹²³^ORCID,Cobat Aurélie¹²³^ORCID,Casanova Jean-Laurent¹²³³¹³²^ORCID,

Affiliation:

1. St. Giles Laboratory of Human Genetics of Infectious Diseases, Rockefeller Branch, The Rockefeller University, New York, NY 1

2. Laboratory of Human Genetics of Infectious Diseases, Necker Branch, INSERM U1163, Paris, France 2

3. University Paris Cité, Imagine Institute, Paris, France 3

4. Laboratory of Virology and Infectious Diseases, The Rockefeller University, New York, NY 4

5. Laboratory of Clinical Immunology and Microbiology, Intramural Research Program, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, MD 6

6. Department of Biosciences and Nutrition, Karolinska Institute, Stockholm, Sweden 7

7. Research Center for Immunodeficiencies, Pediatrics Center of Excellence, Children’s Medical Center, Tehran University of Medical Sciences, Tehran, Iran 8

8. Laboratory for Inborn Errors of Immunity, Department of Microbiology, Immunology and Transplantation, KU Leuven, Leuven, Belgium 5

9. Department of Pediatrics, University Hospitals Leuven, Leuven, Belgium 9

10. Yildirim Beyazit University, Ankara City Hospital, Ankara, Turkey 10

11. Necmettin Erbakan University, Meram Medical Faculty, Division of Pediatric Allergy and Immunology, Konya, Turkey 11

12. Istanbul University-Cerrahpasa, Pediatric Allergy and Immunology, Istanbul, Turkey 12

13. Department of Pediatrics (Infectious Diseases), Istanbul Faculty of Medicine, Istanbul University, Istanbul, Turkey 13

14. Department of Pediatric Immunology and Pulmonology, Department of Internal Medicine and Pediatrics, Centre for Primary Immunodeficiency Ghent, PID Research Laboratory, Jeffrey Modell Diagnosis and Research Centre, Ghent University Hospital, Ghent, Belgium 14

15. Department of Pediatrics, Hôpital de la Citadelle, Liége, Belgium 15

16. Pediatric Infectious Diseases Unit, Bakirkoy Dr. Sadi Konuk Training and Research Hospital, University of Health Sciences, Istanbul, Turkey 16

17. Department of Molecular Biology and Genetics, Bilkent University, Bilkent-Ankara, Turkey 17

18. Department of General Pediatrics, Bicêtre Hospital, Assistance Publique – Hôpitaux de Paris, University of Paris Saclay, Le Kremlin-Bicêtre, France 18

19. Biosciences Institute, University of São Paulo, São Paulo, Brazil 19

20. A*STAR Infectious Diseases Labs (A*STAR ID Labs), Agency for Science, Technology and Research (A*STAR), Singapore, Singapore 20

21. National Centre for Infectious Diseases, Singapore, Singapore 21

22. Lee Kong Chian School of Medicine, Nanyang Technological University, Singapore, Singapore 22

23. Yong Loo Lin School of Medicine, National University of Singapore, Singapore, Singapore 23

24. Tan Tock Seng Hospital, Singapore, Singapore 24

25. The American Genome Center, Uniformed Services University of the Health Sciences, Bethesda, MD 25

26. Department of Anatomy, Physiology & Genetics, Uniformed Services University of the Health Sciences, Bethesda, MD 26

27. Laboratory of Genetics and Genomics, The Rockefeller University, New York, NY 27

28. Department of Genetics, Yale University School of Medicine, New Haven, CT 28

29. Yale Center for Genome Analysis, Yale School of Medicine, New Haven, CT 29

30. School of Biological Sciences, Nanyang Technological University, Singapore, Singapore 30

31. Department of Pediatrics, Necker Hospital for Sick Children, Paris, France 31

32. Howard Hughes Medical Institute, New York, NY 32

Abstract

Recessive or dominant inborn errors of type I interferon (IFN) immunity can underlie critical COVID-19 pneumonia in unvaccinated adults. The risk of COVID-19 pneumonia in unvaccinated children, which is much lower than in unvaccinated adults, remains unexplained. In an international cohort of 112 children (<16 yr old) hospitalized for COVID-19 pneumonia, we report 12 children (10.7%) aged 1.5–13 yr with critical (7 children), severe (3), and moderate (2) pneumonia and 4 of the 15 known clinically recessive and biochemically complete inborn errors of type I IFN immunity: X-linked recessive TLR7 deficiency (7 children) and autosomal recessive IFNAR1 (1), STAT2 (1), or TYK2 (3) deficiencies. Fibroblasts deficient for IFNAR1, STAT2, or TYK2 are highly vulnerable to SARS-CoV-2. These 15 deficiencies were not found in 1,224 children and adults with benign SARS-CoV-2 infection without pneumonia (P = 1.2 × 10−11) and with overlapping age, sex, consanguinity, and ethnicity characteristics. Recessive complete deficiencies of type I IFN immunity may underlie ∼10% of hospitalizations for COVID-19 pneumonia in children.

Funder

Howard Hughes Medical Institute

Rockefeller University

St. Giles Foundation

National Institutes of Health

National Center for Advancing Translational Sciences

Clinical and Translational Science Award

Fast Grant from Emergent Ventures

Mercatus Center at George Mason University

Yale Center for Mendelian Genomics

GSP Coordinating Center

National Human Genome Research Institute