Inborn errors of type I IFN immunity in patients with life-threatening COVID-19-Reference-Cited by-同舟云学术

Inborn errors of type I IFN immunity in patients with life-threatening COVID-19

Published:2020-10-23 Issue:6515 Volume:370 Page:
ISSN:0036-8075
Container-title:Science
language:en
Short-container-title:Science

Author:

Zhang Qian¹^ORCID,Bastard Paul²³^ORCID,Liu Zhiyong¹,Le Pen Jérémie⁴^ORCID,Moncada-Velez Marcela¹^ORCID,Chen Jie¹,Ogishi Masato¹^ORCID,Sabli Ira K. D.⁵^ORCID,Hodeib Stephanie⁵^ORCID,Korol Cecilia²^ORCID,Rosain Jérémie²³,Bilguvar Kaya⁶^ORCID,Ye Junqiang⁷,Bolze Alexandre⁸^ORCID,Bigio Benedetta¹^ORCID,Yang Rui¹^ORCID,Arias Andrés Augusto¹⁹¹⁰^ORCID,Zhou Qinhua¹^ORCID,Zhang Yu¹¹¹²,Onodi Fanny¹³,Korniotis Sarantis¹³,Karpf Léa¹³,Philippot Quentin²³,Chbihi Marwa²³^ORCID,Bonnet-Madin Lucie¹⁴^ORCID,Dorgham Karim¹⁵^ORCID,Smith Nikaïa¹⁶^ORCID,Schneider William M.⁴^ORCID,Razooky Brandon S.⁴^ORCID,Hoffmann Hans-Heinrich⁴^ORCID,Michailidis Eleftherios⁴^ORCID,Moens Leen¹⁷,Han Ji Eun¹^ORCID,Lorenzo Lazaro²³^ORCID,Bizien Lucy²³^ORCID,Meade Philip¹⁸^ORCID,Neehus Anna-Lena²³^ORCID,Ugurbil Aileen Camille¹^ORCID,Corneau Aurélien¹⁹,Kerner Gaspard²³^ORCID,Zhang Peng¹^ORCID,Rapaport Franck¹^ORCID,Seeleuthner Yoann²³,Manry Jeremy²³^ORCID,Masson Cecile²⁰^ORCID,Schmitt Yohann²⁰,Schlüter Agatha²¹^ORCID,Le Voyer Tom²³^ORCID,Khan Taushif²²^ORCID,Li Juan¹,Fellay Jacques²³²⁴²⁵^ORCID,Roussel Lucie²⁶^ORCID,Shahrooei Mohammad²⁷²⁸,Alosaimi Mohammed F.²⁹^ORCID,Mansouri Davood³⁰³¹³²,Al-Saud Haya³³,Al-Mulla Fahd³⁴^ORCID,Almourfi Feras³³^ORCID,Al-Muhsen Saleh Zaid³⁵,Alsohime Fahad²⁹^ORCID,Al Turki Saeed³⁶³⁷^ORCID,Hasanato Rana²⁹^ORCID,van de Beek Diederik³⁸^ORCID,Biondi Andrea³⁹,Bettini Laura Rachele³⁹^ORCID,D’Angio’ Mariella³⁹,Bonfanti Paolo⁴⁰^ORCID,Imberti Luisa⁴¹,Sottini Alessandra⁴¹,Paghera Simone⁴¹,Quiros-Roldan Eugenia⁴²,Rossi Camillo⁴³,Oler Andrew J.⁴⁴^ORCID,Tompkins Miranda F.⁴⁵^ORCID,Alba Camille⁴⁵^ORCID,Vandernoot Isabelle⁴⁶,Goffard Jean-Christophe⁴⁷,Smits Guillaume⁴⁶^ORCID,Migeotte Isabelle⁴⁸,Haerynck Filomeen⁴⁹,Soler-Palacin Pere⁵⁰^ORCID,Martin-Nalda Andrea⁵⁰^ORCID,Colobran Roger⁵¹^ORCID,Morange Pierre-Emmanuel⁵²,Keles Sevgi⁵³,Çölkesen Fatma⁵⁴^ORCID,Ozcelik Tayfun⁵⁵,Yasar Kadriye Kart⁵⁶^ORCID,Senoglu Sevtap⁵⁶^ORCID,Karabela Şemsi Nur⁵⁶^ORCID,Rodríguez-Gallego Carlos⁵⁷⁵⁸^ORCID,Novelli Giuseppe⁵⁹^ORCID,Hraiech Sami⁶⁰,Tandjaoui-Lambiotte Yacine⁶¹⁶²^ORCID,Duval Xavier⁶³⁶⁴,Laouénan Cédric⁶³⁶⁴⁶⁵^ORCID,Snow Andrew L.⁶⁶^ORCID,Dalgard Clifton L.⁴⁵⁶⁷^ORCID,Milner Joshua D.⁶⁸,Vinh Donald C.²⁶^ORCID,Mogensen Trine H.⁶⁹⁷⁰^ORCID,Marr Nico²²⁷¹^ORCID,Spaan András N.¹⁷²^ORCID,Boisson Bertrand¹²³^ORCID,Boisson-Dupuis Stéphanie¹²³^ORCID,Bustamante Jacinta¹²³⁷³^ORCID,Puel Anne¹²³^ORCID,Ciancanelli Michael J.¹⁷⁴^ORCID,Meyts Isabelle¹⁷⁷⁵^ORCID,Maniatis Tom⁷⁷⁶^ORCID,Soumelis Vassili¹³⁷⁷,Amara Ali¹⁴,Nussenzweig Michel⁷⁸⁷⁹^ORCID,García-Sastre Adolfo¹⁸⁸⁰⁸¹⁸²^ORCID,Krammer Florian¹⁸^ORCID,Pujol Aurora²¹^ORCID,Duffy Darragh¹⁶^ORCID,Lifton Richard P.⁸³⁸⁴⁸⁵,Zhang Shen-Ying¹²³,Gorochov Guy¹⁵,Béziat Vivien¹²³^ORCID,Jouanguy Emmanuelle¹²³^ORCID,Sancho-Shimizu Vanessa⁵^ORCID,Rice Charles M.⁴,Abel Laurent¹²³^ORCID,Notarangelo Luigi D.¹¹¹²^ORCID,Cobat Aurélie¹²³^ORCID,Su Helen C.¹¹¹²^ORCID,Casanova Jean-Laurent¹²³⁷⁹⁸⁶^ORCID,Foti Giuseppe,Bellani Giacomo,Citerio Giuseppe,Contro Ernesto,Pesci Alberto,Valsecchi Maria Grazia,Cazzaniga Marina,Abad Jorge,Aguilera-Albesa Sergio,Akcan Ozge Metin,Darazam Ilad Alavi,Aldave Juan C.,Ramos Miquel Alfonso,Nadji Seyed Alireza,Alkan Gulsum,Allardet-Servent Jerome,Allende Luis M.,Alsina Laia,Alyanakian Marie-Alexandra,Amador-Borrero Blanca,Amoura Zahir,Antolí Arnau,Arslan Sevket,Assant Sophie,Auguet Terese,Azot Axelle,Bajolle Fanny,Baldolli Aurélie,Ballester Maite,Feldman Hagit Baris,Barrou Benoit,Beurton Alexandra,Bilbao Agurtzane,Blanchard-Rohner Geraldine,Blanco Ignacio,Blandinières Adeline,Blazquez-Gamero Daniel,Bloomfield Marketa,Bolivar-Prados Mireia,Borie Raphael,Bosteels Cédric,Bousfiha Ahmed A.,Bouvattier Claire,Boyarchuk Oksana,Bueno Maria Rita P.,Bustamante Jacinta,Cáceres Agra Juan José,Calimli Semra,Capra Ruggero,Carrabba Maria,Casasnovas Carlos,Caseris Marion,Castelle Martin,Castelli Francesco,de Vera Martín Castillo,Castro Mateus V.,Catherinot Emilie,Chalumeau Martin,Charbit Bruno,Cheng Matthew P.,Clavé Père,Clotet Bonaventura,Codina Anna,Colkesen Fatih,Çölkesen Fatma,Colobran Roger,Comarmond Cloé,Dalmau David,Darley David Ross,Dauby Nicolas,Dauger Stéphane,de Pontual Loic,Dehban Amin,Delplancq Geoffroy,Demoule Alexandre,Diehl Jean-Luc,Dobbelaere Stephanie,Durand Sophie,Eldars Waleed,Elgamal Mohamed,Elnagdy Marwa H.,Emiroglu Melike,Erdeniz Emine Hafize,Aytekin Selma Erol,Euvrard Romain,Evcen Recep,Fabio Giovanna,Faivre Laurence,Falck Antonin,Fartoukh Muriel,Faure Morgane,Arquero Miguel Fernandez,Flores Carlos,Francois Bruno,Fumadó Victoria,Fusco Francesca,Solis Blanca Garcia,Gaussem Pascale,Gil-Herrera Juana,Gilardin Laurent,Alarcon Monica Girona,Girona-Alarcón Mònica,Goffard Jean-Christophe,Gok Funda,González-Montelongo Rafaela,Guerder Antoine,Gul Yahya,Guner Sukru Nail,Gut Marta,Hadjadj Jérôme,Haerynck Filomeen,Halwani Rabih,Hammarström Lennart,Hatipoglu Nevin,Hernandez-Brito Elisa,Heijmans Cathérine,Holanda-Peña María Soledad,Horcajada Juan Pablo,Hoste Levi,Hoste Eric,Hraiech Sami,Humbert Linda,Iglesias Alejandro D.,Íñigo-Campos Antonio,Jamme Matthieu,Arranz María Jesús,Jordan Iolanda,Jorens Philippe,Kanat Fikret,Kapakli Hasan,Kara Iskender,Karbuz Adem,Yasar Kadriye Kart,Keles Sevgi,Demirkol Yasemin Kendir,Klocperk Adam,Król Zbigniew J.,Kuentz Paul,Kwan Yat Wah M.,Lagier Jean-Christophe,Lambrecht Bart N.,Lau Yu-Lung,Le Bourgeois Fleur,Leo Yee-Sin,Lopez Rafael Leon,Leung Daniel,Levin Michael,Levy Michael,Lévy Romain,Li Zhi,Linglart Agnes,Loeys Bart,Lorenzo-Salazar José M.,Louapre Céline,Lubetzki Catherine,Luyt Charles-Edouard,Lye David C.,Mansouri Davood,Marjani Majid,Pereira Jesus Marquez,Martin Andrea,Pueyo David Martínez,Martinez-Picado Javier,Marzana Iciar,Mathian Alexis,Matos Larissa R. B.,Matthews Gail V.,Mayaux Julien,Mège Jean-Louis,Melki Isabelle,Meritet Jean-François,Metin Ozge,Meyts Isabelle,Mezidi Mehdi,Migeotte Isabelle,Millereux Maude,Mirault Tristan,Mircher Clotilde,Mirsaeidi Mehdi,Melián Abián Montesdeoca,Martinez Antonio Morales,Morange Pierre,Mordacq Clémence,Morelle Guillaume,Mouly Stéphane,Muñoz-Barrera Adrián,Naesens Leslie,Nafati Cyril,Neves João Farela,Ng Lisa F. P.,Medina Yeray Novoa,Cuadros Esmeralda Nuñez,Ocejo-Vinyals J. 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A.,Behillil Sylvie,Bielicki Julia,Bruijning Patricia,Burdet Charles,Caumes Eric,Charpentier Charlotte,Coignard Bruno,Costa Yolande,Couffin-Cadiergues Sandrine,Damond Florence,Dechanet Aline,Delmas Christelle,Descamps Diane,Duval Xavier,Ecobichon Jean-Luc,Enouf Vincent,Espérou Hélène,Frezouls Wahiba,Houhou Nadhira,Ilic-Habensus Emila,Kafif Ouifiya,Kikoine John,Le Hingrat Quentin,Lebeaux David,Leclercq Anne,Lehacaut Jonathan,Letrou Sophie,Lina Bruno,Lucet Jean-Christophe,Malvy Denis,Manchon Pauline,Mandic Milica,Meghadecha Mohamed,Motiejunaite Justina,Nouroudine Mariama,Piquard Valentine,Postolache Andreea,Quintin Caroline,Rexach Jade,Roufai Layidé,Terzian Zaven,Thy Michael,Tubiana Sarah,van der Werf Sylvie,Vignali Valérie,Visseaux Benoit,Yazdanpanah Yazdan,van Agtmael Michiel,Algera Anna Geke,van Baarle Frank,Bax Diane,Beudel Martijn,Bogaard Harm Jan,Bomers Marije,Bos Lieuwe,Botta Michela,de Brabander Justin,de Bree Godelieve,Brouwer Matthijs C.,de Bruin Sanne,Bugiani Marianna,Bulle Esther,Chouchane O.,Cloherty Alex,Elbers Paul,Fleuren Lucas,Geerlings Suzanne,Geerts Bart,Geijtenbeek Theo,Girbes Armand,Goorhuis Bram,Grobusch Martin P.,Hafkamp Florianne,Hagens Laura,Hamann Jorg,Harris Vanessa,Hemke Robert,Hermans Sabine M.,Heunks Leo,Hollmann Markus W.,Horn Janneke,Hovius Joppe W.,de Jong Menno D.,Koning Rutger,van Mourik Niels,Nellen Jeaninne,Paulus Frederique,Peters Edgar,van der Poll Tom,Preckel Benedikt,Prins Jan M.,Raasveld Jorinde,Reijnders Tom,Schinkel Michiel,Schultz Marcus J.,Schuurman Alex,Sigaloff Kim,Smit Marry,Stijnis Cornelis S.,Stilma Willemke,Teunissen Charlotte,Thoral Patrick,Tsonas Anissa,van der Valk Marc,Veelo Denise,Vlaar Alexander P.J.,de Vries Heder,van Vugt Michèle,Wiersinga W. Joost,Wouters Dorien,Zwinderman A. H. (Koos),van de Beek Diederik,Abel Laurent,Aiuti Alessandro,Al Muhsen Saleh,Al-Mulla Fahd,Anderson Mark S.,Arias Andrés Augusto,Feldman Hagit Baris,Bogunovic Dusan,Bolze Alexandre,Bondarenko Anastasiia,Bousfiha Ahmed A.,Brodin Petter,Bryceson Yenan,Bustamante Carlos D.,Butte Manish,Casari Giorgio,Chakravorty Samya,Christodoulou John,Cirulli Elizabeth,Condino-Neto Antonio,Cooper Megan A.,Dalgard Clifton L.,David Alessia,DeRisi Joseph L.,Desai Murkesh,Drolet Beth A.,Espinosa Sara,Fellay Jacques,Flores Carlos,Franco Jose Luis,Gregersen Peter K.,Haerynck Filomeen,Hagin David,Halwani Rabih,Heath Jim,Henrickson Sarah E.,Hsieh Elena,Imai Kohsuke,Itan Yuval,Karamitros Timokratis,Kisand Kai,Ku Cheng-Lung,Lau Yu-Lung,Ling Yun,Lucas Carrie L.,Maniatis Tom,Mansouri Davoud,Marodi Laszlo,Meyts Isabelle,Milner Joshua,Mironska Kristina,Mogensen Trine,Morio Tomohiro,Ng Lisa F. P.,Notarangelo Luigi D.,Novelli Antonio,Novelli Giuseppe,O’Farrelly Cliona,Okada Satoshi,Ozcelik Tayfun,de Diego Rebeca Perez,Planas Anna M.,Prando Carolina,Pujol Aurora,Quintana-Murci Lluis,Renia Laurent,Renieri Alessandra,Rodríguez-Gallego Carlos,Sancho-Shimizu Vanessa,Sankaran Vijay,Barrett Kelly Schiabor,Shahrooei Mohammed,Snow Andrew,Soler-Palacín Pere,Spaan András N.,Tangye Stuart,Turvey Stuart,Uddin Furkan,Uddin Mohammed J.,van de Beek Diederik,Vazquez Sara E.,Vinh Donald C.,von Bernuth Horst,Washington Nicole,Zawadzki Pawel,Su Helen C.,Casanova Jean-Laurent,Jing Huie,Tung Wesley,Luthers Christopher R.,Bauman Bradly M.,Shafer Samantha,Zheng Lixin,Zhang Zinan,Kubo Satoshi,Chauvin Samuel D.,Meguro Kazuyuki,Shaw Elana,Lenardo Michael,Lack Justin,Karlins Eric,Hupalo Daniel M.,Rosenberger John,Sukumar Gauthaman,Wilkerson Matthew D.,Zhang Xijun, , , , , , , ,

Affiliation:

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

2. Laboratory of Human Genetics of Infectious Diseases, Necker Branch, INSERM U1163, Necker Hospital for Sick Children, Paris, France.

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

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

5. Department of Paediatric Infectious Diseases & Virology, Imperial College London, London, UK.

6. Yale Center for Genome Analysis and Department of Genetics, Yale School of Medicine, New Haven, CT, USA.

7. Zukerman Mind Brain Behavior Institute, Columbia University, New York, NY, USA.

8. Helix, San Mateo, CA, USA.

9. Primary Immunodeficiencies Group, University of Antioquia UdeA, Medellin, Colombia.

10. School of Microbiology, University of Antioquia UdeA, Medellin, Colombia.

11. Laboratory of Clinical Immunology and Microbiology, Division of Intramural Research, NIAID, NIH, Bethesda, MD, USA.

12. NIAID Clinical Genomics Program, NIH, Bethesda, MD, USA.

13. Université de Paris, Institut de Recherche Saint-Louis, INSERM U976, Hôpital Saint-Louis, Paris, France.

14. Laboratory of Genomes & Cell Biology of Disease, INSERM U944, CNRS UMR 7212, Université de Paris, Institut de Recherche Saint-Louis, Hôpital Saint-Louis, Paris, France.

15. Sorbonne Université, Inserm, Centre d’Immunologie et des Maladies Infectieuses–Paris (CIMI PARIS), Assistance Publique-Hôpitaux de Paris (AP-HP) Hôpital Pitié-Salpêtrière, Paris, France.

16. Translational Immunology Lab, Institut Pasteur, Paris, France.

17. Laboratory for Inborn Errors of Immunity, Department of Microbiology, Immunology and Transplantation, Department of Pediatrics, University Hospitals Leuven, KU Leuven, Leuven, Belgium.

18. Department of Microbiology, Icahn School of Medicine at Mount Sinai, New York, NY, USA.

19. Sorbonne Université, UMS037, PASS, Plateforme de Cytométrie de la Pitié-Salpêtrière CyPS, Paris, France.

20. Bioinformatics Platform, Structure Fédérative de Recherche Necker, INSERM UMR1163, Université de Paris, Imagine Institute, Paris, France.

21. Neurometabolic Diseases Laboratory, IDIBELL-Hospital Duran i Reynals, CIBERER U759, and Catalan Institution of Research and Advanced Studies (ICREA), Barcelona, Spain.

22. Department of Immunology, Research Branch, Sidra Medicine, Doha, Qatar.

23. School of Life sciences, Ecole Polytechnique Fédérale de Lausanne, Lausanne, Switzerland.

24. Precision Medicine Unit, Lausanne University Hospital and University of Lausanne, Lausanne, Switzerland.

25. Swiss Institue of Bioinformatics, Lausanne, Switzerland.

26. Infectious Disease Susceptibility Program, Research Institute, McGill University Health Centre, Montréal, Québec, Canada.

27. Specialized Immunology Laboratory of Dr. Shahrooei, Sina Medical Complex, Ahvaz, Iran.

28. Department of Microbiology and Immunology, Clinical and Diagnostic Immunology, KU Leuven, Leuven, Belgium.

29. Department of Pathology and Laboratory Medicine, College of Medicine, King Saud University, Riyadh, Saudi Arabia.

30. Department of Clinical Immunology and Infectious Diseases, National Research Institute of Tuberculosis and Lung Diseases, Shahid Beheshti University of Medical Sciences, Tehran, Iran.

31. The Clinical Tuberculosis and Epidemiology Research Center, National Research Institute of, Tuberculosis and Lung Diseases (NRITLD), Masih Daneshvari Hospital, Shahid Beheshti, University of Medical Sciences, Tehran, Iran.

32. Pediatric Respiratory Diseases Research Center, National Research Institute of Tuberculosis and Lung Diseases, Shahid Beheshti, Iran.

33. National Center of Genomics Technology, King Abdulaziz City for Science and Technology, Riyadh, Saudi Arabia.

34. Dasman Diabetes Institute, Department of Genetics and Bioinformatics, Kuwait.

35. Immunology Research Laboratory, Department of Pediatrics, College of Medicine and King Saud University Medical City, King Saud University, Riyadh, Saudi Arabia.

36. Translational Pathology, Department of Pathology and Laboratory Medicine, King Abdulaziz Medical City, Misery of National Guard Health Affairs, Riyadh, Saudi Arabia.

37. Cancer & Blood Research, King Abdullah International Medical Research Center, Riyadh, Saudi Arabia.

38. Amsterdam UMC, Department of Neurology, Amsterdam Neuroscience, Amsterdam, Netherlands.

39. Pediatric Departement and Centro Tettamanti-European Reference Network PaedCan, EuroBloodNet, MetabERN-University of Milano-Bicocca-Fondazione MBBM-Ospedale, San Gerardo, Monza, Italy.

40. Department of Infectious Diseases, San Gerardo Hospital–University of Milano-Bicocca, Monza, Italy.

41. CREA Laboratory, Diagnostic Laboratory, ASST Spedali Civili di Brescia, Brescia, Italy.

42. Department of Infectious and Tropical Diseases, University of Brescia and ASST Spedali di Brescia, Brescia, Italy.

43. Chief Medical Officer, ASST Spedali Civili di Brescia, Brescia, Italy.

44. Bioinformatics and Computational Biosciences Branch, Office of Cyber Infrastructure and Computational Biology, NIAID, NIH, Bethesda, MD, USA.

45. PRIMER, Uniformed Services University of the Health Sciences, Bethesda, MD, USA.

46. Center of Human Genetics, Hôpital Erasme, Université Libre de Bruxelles, Brussels, Belgium.

47. Department of Internal Medicine, Hôpital Erasme, Université Libre de Bruxelles, Brussels, Belgium.

48. Fonds de la Recherche Scientifique (FNRS) and Center of Human Genetics, Hôpital Erasme, Université Libre de Bruxelles, Brussels, Belgium.

49. Department of Paediatric Immunology and Pulmonology, Centre for Primary Immunodeficiency Ghent (CPIG), PID Research Lab, Jeffrey Modell Diagnosis and Research Centre, Ghent University Hospital, Ghent, Belgium.

50. Pediatric Infectious Diseases and Immunodeficiencies Unit, Hospital Universitari Vall d’Hebron, Vall d’Hebron Research Institute, Vall d’Hebron Barcelona Hospital Campus, Universitat Autònoma de Barcelona (UAB), Barcelona, Catalonia, Spain.

51. Immunology Division, Genetics Department, Hospital Universitari Vall d’Hebron, Vall d’Hebron Research Institute, Vall d’Hebron Barcelona Hospital Campus, UAB, Barcelona, Catalonia, Spain.

52. Aix Marseille Univ, INSERM, INRAE, C2VN, CHU Timone, Marseille, France.

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

54. Department of Infectious Diseases and Clinical Microbiology, Konya Training and Research Hospital, Konya, Turkey.

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

56. Departments of Infectious Diseases and Clinical Microbiology, Bakirkoy Dr. Sadi Konuk Training and Research Hospital, University of Health Sciences, Istanbul, Turkey.

57. Department of Immunology, Hospital Universitario de G.C. Dr. Negrín, Canarian Health System, Las Palmas de Gran Canaria, Spain.

58. University Fernando Pessoa Canarias, Las Palmas de Gran Canaria, Spain.

59. Department of Biomedicine and Prevention, University of Rome “Tor Vergata,” Rome, Italy.

60. Intensive Care Unit, AP-HM, Marseille, France.

61. Avicenne Hospital Intensive Care Unit, APHP, Bobigny, INSERM U1272 Hypoxia & Lung, Paris, France.

62. PH Réanimation CHU Avicenne, Bobigny, INSERM U1272 Hypoxie & Poumon, Paris, France.

63. Université de Paris, IAME UMR-S 1137, INSERM, Paris, France.

64. Inserm CIC 1425, Paris, France.

65. AP-HP, Département Epidémiologie Biostatistiques et Recherche Clinique, Hôpital Bichat, Paris, France.

66. Department of Pharmacology & Molecular Therapeutics, Uniformed Services University of the Health Sciences, Bethesda, MD, USA.

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

68. Division of Pediatric Allergy, Immunology and Rheumatology, Columbia University, New York, USA.

69. Department of Infectious Diseases, Aarhus University Hospital, Skejby, Denmark.

70. Department of Biomedicine, Aarhus University, Aarhus, Denmark.

71. College of Health and Life Sciences, Hamad Bin Khalifa University, Doha, Qatar.

72. Department of Medical Microbiology, Utrecht UMC, Utrecht, Netherlands.

73. Study Center for Primary Immunodeficiencies, Necker Hospital for Sick Children, Paris, France.

74. Turnstone Biologics, New York, NY, USA.

75. Department of Pediatrics, University Hospitals Leuven, KU Leuven, Leuven, Belgium.

76. New York Genome Center, New York, NY, USA.

77. AP-HP, Hôpital Saint-Louis, Laboratoire d’Immunologie, Paris, France.

78. Laboratory of Molecular Immunology, Rockefeller University, New York, NY, USA.

79. Howard Hughes Medical Institute, New York, NY, USA.

80. Department of Medicine, Division of Infectious Diseases, Icahn School of Medicine at Mount Sinai, New York, NY, USA.

81. Global Health and Emerging Pathogens Institute, Icahn School of Medicine at Mount Sinai, New York, NY, USA.

82. The Tisch Cancer Institute, Icahn School of Medicine at Mount Sinai, New York, NY, USA.

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

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

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

86. Pediatric Hematology and Immunology Unit, Necker Hospital for Sick Children, AP-HP, Paris, France.

Abstract

The genetics underlying severe COVID-19 The immune system is complex and involves many genes, including those that encode cytokines known as interferons (IFNs). Individuals that lack specific IFNs can be more susceptible to infectious diseases. Furthermore, the autoantibody system dampens IFN response to prevent damage from pathogen-induced inflammation. Two studies now examine the likelihood that genetics affects the risk of severe coronavirus disease 2019 (COVID-19) through components of this system (see the Perspective by Beck and Aksentijevich). Q. Zhang et al. used a candidate gene approach and identified patients with severe COVID-19 who have mutations in genes involved in the regulation of type I and III IFN immunity. They found enrichment of these genes in patients and conclude that genetics may determine the clinical course of the infection. Bastard et al. identified individuals with high titers of neutralizing autoantibodies against type I IFN-α2 and IFN-ω in about 10% of patients with severe COVID-19 pneumonia. These autoantibodies were not found either in infected people who were asymptomatic or had milder phenotype or in healthy individuals. Together, these studies identify a means by which individuals at highest risk of life-threatening COVID-19 can be identified. Science , this issue p. eabd4570 , p. eabd4585 ; see also p. 404

Funder

National Institutes of Health

Howard Hughes Medical Institute

ST. GILES FOUNDATION

National Center for Advancing Translational Sciences

Rockefeller University

French National Research Agency

the Integrative Biology of Emerging Infectious Diseases Laboratory of Excellence

National Human Genome Research Institute

the French Foundation for Medical Research

NIH Clinical and Translational Science Award

Emergent Ventures

Publisher

American Association for the Advancement of Science (AAAS)

Subject

Multidisciplinary

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